METHADONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Methadone: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83716-3 1. Methadone-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on methadone. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON METHADONE ............................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Methadone..................................................................................... 4 E-Journals: PubMed Central ..................................................................................................... 111 The National Library of Medicine: PubMed .............................................................................. 112 CHAPTER 2. NUTRITION AND METHADONE ................................................................................ 239 Overview.................................................................................................................................... 239 Finding Nutrition Studies on Methadone ................................................................................. 239 Federal Resources on Nutrition ................................................................................................. 245 Additional Web Resources ......................................................................................................... 245 CHAPTER 3. ALTERNATIVE MEDICINE AND METHADONE .......................................................... 247 Overview.................................................................................................................................... 247 National Center for Complementary and Alternative Medicine................................................ 247 Additional Web Resources ......................................................................................................... 253 General References ..................................................................................................................... 254 CHAPTER 4. DISSERTATIONS ON METHADONE ............................................................................ 255 Overview.................................................................................................................................... 255 Dissertations on Methadone ...................................................................................................... 255 Keeping Current ........................................................................................................................ 260 CHAPTER 5. CLINICAL TRIALS AND METHADONE ....................................................................... 261 Overview.................................................................................................................................... 261 Recent Trials on Methadone ...................................................................................................... 261 Keeping Current on Clinical Trials ........................................................................................... 266 CHAPTER 6. BOOKS ON METHADONE .......................................................................................... 269 Overview.................................................................................................................................... 269 Book Summaries: Federal Agencies............................................................................................ 269 The National Library of Medicine Book Index ........................................................................... 274 Chapters on Methadone ............................................................................................................. 275 CHAPTER 7. MULTIMEDIA ON METHADONE ................................................................................ 277 Overview.................................................................................................................................... 277 Video Recordings ....................................................................................................................... 277 Audio Recordings....................................................................................................................... 278 Bibliography: Multimedia on Methadone .................................................................................. 279 CHAPTER 8. PERIODICALS AND NEWS ON METHADONE ............................................................. 281 Overview.................................................................................................................................... 281 News Services and Press Releases.............................................................................................. 281 Academic Periodicals covering Methadone................................................................................ 285 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 287 Overview.................................................................................................................................... 287 U.S. Pharmacopeia..................................................................................................................... 287 Commercial Databases ............................................................................................................... 288 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 291 Overview.................................................................................................................................... 291 NIH Guidelines.......................................................................................................................... 291 NIH Databases........................................................................................................................... 293 Other Commercial Databases..................................................................................................... 297 APPENDIX B. PATIENT RESOURCES ............................................................................................... 299 Overview.................................................................................................................................... 299 Patient Guideline Sources.......................................................................................................... 299
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Associations and Methadone...................................................................................................... 307 Finding Associations.................................................................................................................. 308 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 311 Overview.................................................................................................................................... 311 Preparation................................................................................................................................. 311 Finding a Local Medical Library................................................................................................ 311 Medical Libraries in the U.S. and Canada ................................................................................. 311 ONLINE GLOSSARIES................................................................................................................ 317 Online Dictionary Directories ................................................................................................... 318 METHADONE DICTIONARY.................................................................................................... 319 INDEX .............................................................................................................................................. 387
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with methadone is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about methadone, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to methadone, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on methadone. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to methadone, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on methadone. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON METHADONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on methadone.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and methadone, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “methadone” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Methylnaltrexone for Reversal of Constipation Due to Chronic Methadone Use: A Randomized Controlled Trial Source: JAMA. Journal of American Medical Association. 283(3): 367-372. January 19, 2000. Summary: Constipation is the most common chronic adverse effect of opioid pain medications in patients who require long term opioid administration, such as patients with advanced cancer, but conventional measures for ameliorating constipation often are insufficient. This article reports on a study undertaken to evaluate the efficacy of methylnaltrexone, the first peripheral opioid receptor antagonist, in treating chronic methadone induced constipation. The double blind, randomized placebo controlled trial was conducted between May 1997 and December 1998 at the clinical research center of a university hospital. The subjects (n = 22, 9 men and 13 women) had a mean age of 43.2
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years and were enrolled in a methadone maintenance program and had methadone induced constipation. The 11 subjects in the placebo group showed no laxation response, and all 11 subjects in the intervention group had laxation response after intravenous methylnaltrexone administration. The oral cecal transit times at baseline for subjects in the treatment and placebo groups averaged 132.3 and 126.8 minutes, respectively. The average (standard deviation) change in the treatment group was minus 77.7 minutes, significantly greater than the average change in the placebo group of minus 1.4 minutes. No opioid withdrawal was observed in any subject, and no significant adverse effects were reported by the subjects during the study. The authors conclude that intravenous methylnaltrexone can induce laxation and reverse slowing of oral cecal transit time in subjects taking high opioid dosages. Low dosage methylnaltrexone may have clinical utility in managing opioid induced constipation. 3 figures. 1 table. 37 references. •
The Effect of Methadone on Immunological Parameters Among HIV - Positive and HIV - Negative Drug Users Source: American Journal of Drug Alcohol Abuse; Vol. 20, No. 3. Contact: New York State Psychiatric Institute, HIV Center for Clinical and Behavioral Studies, 1051 Riverside Dr PI Unit 15, New York, NY, 10032, (212) 543-5969, http://www.hivcenternyc.org. Summary: This journal article describes a 5-year observational study designed to investigate the effects of methadone use on immune parameters. The 220 participants were current or former drug injectors who knew their HIV serostatus. The paper compares absolute and percentage counts of CD4, CD8, and activated T lymphocytes; CD4/CD8 ratio; an HIV symptom checklist; and medical staging of methadone users with non-methadone users. It indicates that regardless of HIV serostatus, methadone treatment is associated with lower CD4 percentage, lower CD4/CD8 ratio, and higher CD8 absolute count and percentage. The authors suggest the need for corroboration of their findings and emphasize the study was not designed to investigate the effects of methadone on the immune system.
Federally Funded Research on Methadone The U.S. Government supports a variety of research studies relating to methadone. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to methadone. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use 2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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animals or simulated models to explore methadone. The following is typical of the type of information found when searching the CRISP database for methadone: •
Project Title: A PRIMATE MODEL OF DRUG ABUSE: INTERVENTION STRATEGIES Principal Investigator & Institution: Carroll, Marilyn E. Professor of Psychiatry and Neuroscience; Psychiatry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 01-JAN-1980; Project End 31-MAR-2006 Summary: Goals of the proposed research are to use a rhesus monkey model of drug abuse, to study factors affecting vulnerability to drug abuse and to evaluate behavioral and pharmacological treatment interventions. Routes of administration that have been developed in this laboratory will include oral drug self-administration and smoking. When using the oral route of self-administration, liquid deliveries are contingent upon lip-contact responses. Smoke deliveries are contingent upon inhalation responses. Vulnerability factors to be examined are sex and phase of the menstrual cycle as well as patterns/duration of access to drugs. Initial work indicates that escalation from drug use to abuse is dependent upon the amount and duration of access. The proposed work will extend these findings to monkeys, other drugs, and measures of reinforcing efficacy. In addition, the question of whether differential access to one drug affects acquisition of self-administration of a second drug will be examined. Well-accepted measures of the reinforcing efficacy of drugs, behavioral economic demand curve analyses and PR schedules will be used to determine how these predisposing factors ultimately affect the reinforcing potential of selected drugs. The drugs that will be studied are cocaine, ethanol, heroin, methadone and phencyclidine (PCP). Behavior maintained by food and/or liquid saccharin will be used as a control for drug-selective effects. The behavioral economic measures will also be used quantify the extent to which these drug and nondrug substances substitute for each other. These studies will inform us about the effectiveness of substituting nondrug items for drugs in treatment, as well for predicting polydrug abuse by how well one form of drug abuse substitutes for another. The use of nondrug reinforcers as a behavioral treatment will also be compared in male and female monkeys and during 3 phases of the menstrual cycle. Potential treatment medications will also be examined in male monkeys using a behavioral economic approach. Three different types of drugs that have produced promising preliminary results are proposed: bremazocine, an agonist at the kappa opioid receptor, baclofen, a GABAB agonist, and ketoconazole, an inhibitor of corticosterone synthesis. Finally, the behavioral (alternative reinforcer) and pharmacological treatments will be combined and compared to the effects of each given alone. The results of the proposed 11 experiments will provide valuable information about major vulnerability factors and several behavioral and pharmacological treatment approaches for drug abuse. It is hoped that this information will lead to earlier and more effective prevention and treatment of drug abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A REINFORCEMENT-BASED THERAPEUTIC WORKPLACE Principal Investigator & Institution: Silverman, Kenneth; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2007
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Summary: (provided by applicant) The Therapeutic Workplace is a novel treatment designed to address the chronic and persistent nature of drug addiction and unemployment. Under this intervention, drug abuse patients are hired and paid to work in an income-producing Therapeutic Workplace business. To promote abstinence, participants are required to provide drug-free urine samples to maintain daily access to the workplace. Applicants actively using drugs and lacking job skills participate in an initial training phase to initiate abstinence and establish job skills. If the business is financially successful, this treatment could be maintained over extended periods of time at little cost to society. This application is a competing continuation of a grant in which we developed and pilot tested a computerized Therapeutic Workplace designed to train and employ adults as data entry operators. A randomized trial is planned over 5 years to investigate the Therapeutic Workplace business as a maintenance intervention to sustain long-term abstinence and employment. Welfare recipients in methadone treatment, actively using cocaine, and at risk for contracting or spreading HIV infection will participate in an initial Therapeutic Workplace training phase. Participants (N=156) who become abstinent and skilled will be randomly assigned to a "Usual Care Control," an "Employment Only," or an "Abstinence & Employment" group. "Usual Care Control" participants will be referred to seek a job in the community. "Employment Only" participants will be offered employment for one year in a Therapeutic Workplace business, but these participants will not have to provide drug-free urine samples to work. Participants in the "Abstinence & Employment" group will be employed for one year also, but these participants will have to provide drug-free urine samples to work and earn salary. This study will provide a rigorous evaluation of the efficacy of the Therapeutic Workplace business as a long-term treatment of cocaine addiction and unemployment; determine the benefits of requiring daily evidence of abstinence to work; and provide information on the extent to which a Therapeutic Workplace business can become self-sustaining. This research could provide firm scientific foundation for the dissemination of Therapeutic Workplace businesses in the long-term treatment of cocaine addiction and unemployment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACUPUNCTURE AND COPING SKILLS TRAINING FOR COCAINE ABUSE Principal Investigator & Institution: Margolin, Arthur; Research Scientist; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 15-SEP-1994; Project End 31-AUG-2005 Summary: (Applicant's Abstract) This competing renewal requests funds to continue our research investigating auricular acupuncture as a treatment for cocaine addiction. In the previous grant period we conducted three clinical studies enrolling 211 patients. Each study compared auricular acupuncture to two control conditions - a needle insertion control using sites in the auricle helix, and a relaxation group - under a variety of conditions, with and without a widely used psychosocial treatment (Coping Skills Training - CST) as well as financial incentives for attendance. Findings supported the efficacy of acupuncture when provided in conjunction with CST and without financial incentives. However, these studies were not designed to definitively examine the interaction between acupuncture and CST, or to determine whether acupuncture is more effective than CST delivered alone. The proposed study builds upon our previous research and will investigate two widely used treatments and their interactions acupuncture and CST - in a clinical context in which each treatment is provided by substance abuse counselors, employing a research design consistent with the need to
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bring research findings to clinical practice, and in which relative cost of each treatment is also considered. We propose to conduct a "Phase III" clinical trial in which 200 cocaine-abusing methadone maintained patients, all receiving standard methadone maintenance treatment, will be randomly assigned to 4 treatment conditions, each of 12 weeks duration, in a 2 (acupuncture/no acupuncture) by 2 (weekly coping skills training group/no coping skills training) factorial design. The four groups are: (a) acupuncture only (ACU); (b) coping skills training only (CST); (c) acupuncture plus coping skills training (ACU+CST); (d) standard methadone maintenance only (MM). In a second phase of the study, in order to explore the effectiveness of these treatments in preventing relapse, patients who initiate abstinence in the 12-week trial will be invited to continue their assigned treatment for 6 months. Both clinical efficacy, cost, as well as treatment/patient matching variables, will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACUTE DRUG WITHDRAWAL IN A GENERAL MEDICAL SETTING Principal Investigator & Institution: Weaver, Michael F. Internal Medicine; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: This is a proposal for a Mentored Clinical Scientist Development Award to provide supervised experience in clinical research, didactic education, and some clinical activities. This will provide a foundation for a career in academic medicine with opportunities for research, teaching, and some clinical practice. This award will allow the candidate to begin research in substance abuse treatment and Health Services Research (HSR) in a supervised setting. The effects of symptom-triggered therapy versus scheduled dosing for acute withdrawal from alcohol will be studied in a general medical population. The first two years of the award period will be spent taking graduate courses in biostatistics, pharmacology, research design and methodology, attending seminars on HSR topics, and refining the final study protocol by doing a pilot study. Practical clinical experience will be gained in outpatient clinics including rotation through community programs such as a local methadone maintenance clinic, a residential center for pregnant and newly delivered women and their young children, and inpatient substance abuse services in a large urban teaching hospital. Symptomtriggered therapy with benzodiazepines is the treatment of choice for alcohol withdrawal. It has not been studied in a general medical population. Patients admitted to two general medical wards will be assigned as randomly as possible to symptomtriggered or scheduled therapy for acute alcohol withdrawal. They will be regularly assessed by a clinical assessment tool to evaluate its applicability in this population. Data will be collected on concurrent medical problems, total dose of medication for withdrawal, duration of treatment, complications, length of stay, and recidivism. The medication protocols will be evaluated in terms of acceptance by nurses and physicians, especially housestaff. The data will be evaluated from a HSR standpoint to help determine the most cost-effective regimen for acute drug withdrawal in a general medical population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADDICTION MEDICINE PHYSICIANS AND CARE FOR HEPATITIS C Principal Investigator & Institution: Gourevitch, Marc N. Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, NY 10033
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Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Drug users are heavily and disproportionately affected by hepatitis C, yet they face numerous barriers to healthcare that place them at risk for substantially lower levels of hepatitis C care than non-drug users. Because of their continuous contact with individual drug users and their knowledge of and experience with the intricacies of their healthcare, physicians practicing addiction medicine are in a unique position to facilitate drug users' access to and success with hepatitis C treatment. However, no data exists to describe the knowledge, attitudes and experience of addiction medicine physicians regarding hepatitis C care for drug users. We propose to nationwide survey of over 800 physician members of the American Society of Addiction Medicine (ASAM). Non-ASAM physicians practicing medicine in methadone maintenance treatment programs New York State will also be surveyed and compared to ASAM members to determine the generalizability of findings derived from the latter cohort. The proposed study will address the following specific aims: Aim 1: To describe the knowledge of and attitudes towards eligibility guidelines for hepatitis C treatment among physicians in addiction medicine, and determine the association between these attitudes and the physicians' provision of hepatitis C treatment to DUs, either direct or by referral; Aim 2: To determine the association between provision of HIV care by physicians in addiction medicine and the provision of hepatitis C treatment to DUs, either direct or by referral; Aim 3: To determine the association between the availability of onsite primary medical care in drug treatment programs and provision of hepatitis C treatment to DUs, either direct or by referral, by physicians in addiction medicine. The survey will focus on physicians' knowledge and attitudes surrounding treatment eligibility criteria, such as duration of abstinence from drug and alcohol use and history of depression. It will query physicians about their experience with hepatitis C treatment for drug users, either by referral or by direct management themselves, and their access to treatment resources. It will also inquire about their clinical practice setting and their professional background. The proposed study will identify strengths and weaknesses in the delivery of hepatitis C healthcare by addiction medicine physicians to drug users, and it will focus on collecting data useful for the development of interventions designed to improve drug users' access to hepatitis C treatment. Data from this study will have relevance to both drug abuse treatment policy and clinical practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADDRESSING NICOTINE ADDICTION IN DRUG ABUSE PATIENTS Principal Investigator & Institution: Richter, Kimber; Psychology and Sociology; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 05-FEB-2000; Project End 31-JAN-2005 Summary: Kimber P. Richter, Ph.D., M.P.H., is a behavioral psychologist with training in public health who will use the MRSDA to develop expertise in addressing nicotine addiction among persons in drug abuse treatment, an estimated 80 percent of whom smoke. The proposal combines her behavioral background in drug abuse prevention, drug abuse treatment, and cardiovascular disease risk reduction with a new focus on smoking cessation. This plan outlines the training and research experience she will need, over the next 5 years, to develop and launch a fully independent career addressing nicotine addiction among persons in drug abuse treatment. Career Development: Activities include training in the chemistry of the nervous system, advanced biostatistics, training in addictions treatment and research, a week-long internship with a nicotine/drug addictions researcher, and an intensive bioethics course. Research Program: The goal of the proposed research program is to better understand smoking
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behaviors and nicotine dependence among persons in treatment for chemical dependencies, and to identify acceptable and potentially effective methods for reducing cigarette smoking in this population. Specifically, the plan involves three studies that address five research questions. Study 1 examines key issues in smoking cessation from the patient's point of view. It consists of a series of two focus groups among each of four subgroups of clients in methadone maintenance treatment (MMT) and other drug dependency programs. These 8 sessions is will identify clients' a) interest in quitting, b) barriers to quitting smoking, c) successful strategies used to quit smoking, d) strategies used to avoid illicit drug use that might be adapted for smoking cessation, and e) treatment preferences for quitting smoking. Study 2 is a descriptive study examining interactions in patterns of cigarette use and methadone maintenance. Twenty-one methadone patients will use electronic monitors to record the frequency and timing of their cigarette consumption. Data on methadone timing and dose, as well as carbon monoxide levels and psychological measures of nicotine craving and withdrawal, will be collected and analyzed to assess whether methadone dose and timing are associated with surges in cigarette consumption and smoking urges. Study 3 is a pilot study examining the feasibility and potential efficacy of a multicomponent intervention on smoking cessation. Sixty MMT patients will be randomly assigned to treatment (nicotine inhaler and motivational interviewing) or control (placebo inhaler and comparable staff contact). Primary outcomes include quit rates and avg. daily cigarette use. Pilot data will allow determination of sample sizes for a full-scale intervention trial, and will be used to assess the effects of variables such as age, gender, methadone dose on treatment effects. The research plan uses exploratory, descriptive, and intervention research to address fundamental issues of nicotine addiction. Each study stands on its own, but is designed to build on the findings of the prior study. This research may serve as a model for systematic research on nicotine addiction in patients with other drugs of dependence or who are in other drug abuse treatment modes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADOPTION OF BUPHENORPHINE IN OFFICE PRACTICE Principal Investigator & Institution: Wallack, Stanley S. None; Brandeis University 415 South Street Waltham, MA 024549110 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): In October, 2000 the Drug Addiction Treatment Act of 2000 was passed and signed into law, allowing qualified physicians to dispense or prescribe certain narcotic drugs for maintenance or detoxification treatment. According to this legislation, once buprenorphine, a maintenance medication for treatment of opiate addiction, receives FDA approval, physicians may be certified to prescribe it in office practice. Until now physicians have been prohibited from dispensing buprenorphine for opiate addiction, despite evidence of its effectiveness. This legislation is expected to improve access to treatment for thousands who are addicted to opiates by bringing into treatment both people who have rejected use of methadone and for whom methadone has failed, and physicians who wish to treat opiate dependent individuals who are appropriate for office-based treatment. Despite evidence that buprenorphine offers a needed treatment alternative, recent legislative changes and FDA approval alone may not lead to improved access for addicts. For instance, naltrexone, a pharmacological approach to alcoholism treatment, has seen limited acceptance in practice, in spite of clinical evidence of effectiveness and support of policy makers and experts. The factors contributing to the low rates of acceptance are not fully understood, but there is strong evidence that lack of financing and provider knowledge were two
10 Methadone
main barriers to naltrexone diffusion. These same factors could undermine buprenorphine diffusion into clinical practice. The proposed study seeks to understand factors related to adoption of buprenorphine in office-based practice by surveying a national sample of addiction specialists and general psychiatrists regarding their decision to prescribe buprenorphine or not, and surveying treatment settings regarding adoption and use of buprenorphine. We will examine characteristics of the clinicians, the treatment settings, and financing programs with which they are associated, in order to understand factors associated with moving research to practice, and the links between physicians and their treatment settings in deciding to adopt new treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AN ABEF SYNTHON FOR NORDITERPENOID ALKALOIDS Principal Investigator & Institution: Lewis, David E. Chemistry; University of Wisconsin Eau Claire Eau Claire, WI 54701 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2004 Summary: (Principal Investigator's Abstract) In 1991 and 1992, patents were issued in the United States and in Great Britain for the use of certain C19 diterpenoid alkaloids for both the treatment of narcotic addiction and for alleviation of symptoms arising from the withdrawal syndrome encountered with opiate addicts. Due to their non-narcotic nature, these compounds may offer considerable promise for impacting favorably on the limitations of contemporary maintenance programs which remain centered around the controlled administration of substitute narcotics such as methadone.. The long-term goal for the research proposed herein is to develop a new strategy for the total synthesis of these alkaloids which could make synthetic compounds to be readily available to support laboratory investigation and controlled pre-clinical pharmacological studies of their antinociceptive activity for treating narcotic addiction. It is expected that this longterm goal will be addressed in five stages. This proposal will explicitly address the first stage. Its specific aim is to develop one or more efficient routes for the total synthesis of a simple tetracyclic ABEF synthon to demonstrate the feasibility of the key early cyclization steps of the proposed overall synthetic strategy. ln the proposed work, the synthesis of the tetracyclic synthon will be carried out by sequential intramolecular phenoxy radical coupling, Michael addition and aldol addition reactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANALYSIS OF MEDICATIONS FOR THE PREGNANT OPIATE ADDICT Principal Investigator & Institution: Ahmed, Mahmoud S. Pharmaceutical Sciences; University of Missouri Kansas City Kansas City, MO 64110 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 28-FEB-2002 Summary: The long term goal of our investigations is to improve on the treatment of the pregnant opiate addict and the outcome of their newborns. For several decades, the only treatment available for these patients were methadone programs. These programs have been successful and methadone became the "standard" for treating the heroin and morphine addict. However, relapses, side effects, drug interactions and unexplained clinical observations were reported and prompted investigators to seek alternative drugs. Two such drugs, buprenorphine (BUP) and L-acetylmethadol (LAAM) are currently available but data on their effects on the pregnant patient and her newborn are scarce to non-existent. The goal of this investigation is to provide the needed basic information on BUP and LAAM for their safe use in treatment of the pregnant opiate
Studies 11
addict as well as help understand several unexplained observations associated with these patients and their newborns in methadone programs. The hypothesis for our investigation is that the three opiates, because of their physicochemical properties, may be transported by passive diffusion across the placenta from the maternal to fetal circulation. However, human placenta plays an important role in protecting the fetus from exposure to drugs, xenobiotics and environmental pollutants. This role can be achieved either by metabolizing the drug or extruding it to the maternal circulation by the transporter P-glycoprotein (P-gp). Our data will determine if either of these functions affects the transfer of these opiates to the fetal circulation. The technique of dual perfusion of human placental lobule will be utilized to obtain these data. The placentas utilized will be obtained from full term healthy pregnancies. The specific aims for the proposed work are: (1) Determine the transplacental transfer (TPT) parameters for BUP, LAAM and methadone.. (2) Determine the metabolites formed for each opiate by placental tissue and their subsequent distribution between the tissue, maternal and fetal circulations. (3) Identify which of the opiates is a substrate for P-gp. Data obtained may provide the cause for several unexplained clinical observations associated with treatment of this patient population. These include: withdrawal symptoms, and severity, observed in some but not all newborns for mothers treated with BUP or methadone during pregnancy; lack of correlation between dose of the drug and its maternal serum levels; lower concentrations of the opiate and metabolites in pregnant than nonpregnant patients. Identification of the opiate substrate for P-gp will allow avoiding drug interactions with other medications thus avoiding fetal over exposure to both. In summary, the information obtained will provide a better understanding of the transfer of these opiates across human placenta and the role of the tissue in decreasing fetal exposure to the drugs. It may also provide a choice of medications for treating an individual patient according to her condition thus improving neonatal outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIRETROVIRAL THERAPIES AND SUBSTANCE ABUSE Principal Investigator & Institution: Greenblatt, David J. Professor and Chair; Pharmacol & Exper Therapeutics; Tufts University Boston Boston, MA 02111 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract) Substance abuse among patients with human immunodeficiency virus (HIV) infection is a matter of major public health concern. Some 25-30 percent of HIV-infected patients have acquired the disease through IV. drug-use; a principal therapeutic objective is to sustain abstinence, both for patients' health and to minimize risk of disease dissemination, through maintenance programs using methadone or buprenorphine. For these and other HIV-infected patients, the emotional burden of the disease produces comorbidity with depression, anxiety, and sleep disorders. Benzodiazepine agonists are commonly prescribe for anxiety and insomnia, and there is concern regarding abuse of this class of drugs. Highly active antiretroviral therapies (HAART), including the HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), constitute major advances in the treatment of HIV infecffon, but greatly complicate the link between HIV/AID' and substance abuse. HIV PIs and NNRTls may inhibit and/or induce the activity of human Cytochrome P4503A (CYP3A) enzymes, responsible for the metabolism of buprenorphine, methadone, many benzodiazepines and for the formation of the hepatotoxic metabolite of cocaine. CYP3A inhibition could promote methadone toxicity, or enhance abusability of benzodiazopines; CYP3A induction could precipitate methadone withdrawal and opiate relapse, or enhance cocaine hepatotoxicity. The
12 Methadone
applicants propose to apply in vitromodels, using human liver microsomal preparations, to determine the capacity of HIV PIs (ritonavir, nelfinavir, indinavir, saquinavir) and of NNRTls tdelavirdine, nevirapine, efavirenz) to inhibit CYP3Amediated metabolism of methadone, buprenorphine, triazolam, alprazolam, flunitrazepam, and cocaine. In vitro in vivoscaling paradigms will be used to estimate the probability of clinically important in vivointeractions. The validity of the model will be prospectively tested in controlled clinical pharmacokinetic-pharmacodynamic studies of triazolam coadministered with ritonavir or delavirdine, and of methadone coadministered with thes' same two HMRT drugs. The time-course and extent of CYP3A induction by ritonavir, and the net balance of inhibition and induction, are tested in a controlled study of triazolam kinetics and dynamics before, during, and after extended exposure to ritonavir. The in vitro model, if validated, has the potential to provide clinically important information on interactions involving HIV treatments and abusable drugs, at relatively low cost and with no human drug exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL DEPENDENCE
STUDIES
OF
OPIOID
TOLERANCE
AND
Principal Investigator & Institution: Young, Alice M. Professor; Psychology; Wayne State University 656 W. Kirby Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 30-JUN-2002 Summary: (Applicant's Abstract) Current treatments for human opioid abuse incorporate a variety of chronic pharmacotherapies, including methadone maintenance and newer or experimental treatments with low efficacy opioid agonists (e.g., buprenorphine) or opioid antagonists (e.g., naltrexone). Preclinical studies of the behavioral sequelae of such maintenance therapies may be useful in predicting their psychomotor and subjective effects in humans. The proposed projects will use drug discrimination assays as a model system to assess how pharmacological and behavioral factors modulate development of tolerance during repeated treatment with selected opioid agonists, alone and in combination with non-opioid agents proposed to modulate opioid tolerance and/or dependence. We will pay particular attention to patterns of tolerance and cross-tolerance among opioids that appear to differ in intrinsic efficacy as agonists. Related experiments will evaluate several behavioral effects of opioids in opioid-dependent subjects, and in subjects treated with irreversible opioid receptor antagonists. The first proposed project will characterize patterns of tolerance and crosstolerance to discriminative stimulus and antinociceptive effects of mu opioids as a function of agonist efficacy. Planned studies will focus on chronic administration of low efficacy mu agonists. The second project will study antagonism of antinociceptive and stimulus effects of agonists by irreversible antagonists, in order to provide an independent test of the hypothesis that differences in tolerance are related to differences in relative intrinsic efficacy. The third and fourth projects will characterize acute and chronic interventions that may modulate development of opioid tolerance or dependence. Specific compounds to be studied include putative neutral opioid antagonists, kinase inhibitors, NMDA-antagonists CCK-antagonists and NO synthase inhibitors. Experiments will determine effects of acute and chronic treatment with selected agents on development and expression of tolerance and dependence, using behavioral assays of antinociception, acute dependence, and discriminative stimulus effects of mu opioids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 13
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Project Title: BEHAVIORAL STUDIES WITH METHADONE CLIENTS Principal Investigator & Institution: Greenwald, Mark K. Assistant Profess or of Psychiatry and b; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 15-APR-1997; Project End 31-MAR-2003 Summary: Drug craving (desire to re-experience effects of a psychoactive substance) is an internal motivational state that can be measured objectively. The mechanisms that underlie drug craving and mediate illicit drug-taking behavior are poorly understood, but are important to improving treatment and health status. The overall aim of this research is to determine the effects of several pharmacological and environmental variables on heroin craving in methadone-maintained clients. We have previously shown that naloxone-precipitated withdrawal in methadone clients is accompanied by increased heroin craving, using a new multifactor scale (Heroin Craving Questionnaire [HCQ]). These systematic and interrelated studies will extend our work on the determinants of craving during anticipation of drug reinforcement in methadonemalntained clients, in an effort to increase our understanding of the detenninants of drug craving and their clinical consequences. Specific questions are: (Study 1) Does methadone decrease opioid craving? Is craving reduction a function of time in treatment or medication dose? Do different methadone exposure histories produce differences in craving? Is methadone's effect on craving pharmacologically specific? Do individual differences methadone pharmacokinetics influence craving?(study 2) Do the magnitude/pattern of opioid craving and brain electrophysiology differ during anticipation of i.v. opioid self-administration under conditions of opioid withdrawal (negative reinforcement) versus after low priming doses of fentanyl (positive reinforcement)? Are these changes specific to receiving a drug, or do similar changes occur in preparation to receive other reinforcers (money)?; (Study 3) Do increases in the delay of methadone delivery increase opioid craving? Is craving attenuated by work activity during the delay period?; (Study 4) Does methadone availability alter heroin craving, i.e., do changes in the magnitude of the dose and probability of receiving a drug dose affect craving during anticipation of its delivery?; (All Studies) Do the a priori (conceptual) subscales vs. empirically-derived factor scores of the HCQ provide a more sensitive index of craving effects? These studies are responsive to the RFA and will be clinically useful. Broader insights into the affective, cognitive and behavioral components of drug incentive motivation are likely to result, and the behavioral principles and methods advanced here can guide future research on craving for cocaine and other drugs of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BEHAVIORAL DEPENDENCE
THERAPY
FOR
DEPRESSION
IN
DRUG
Principal Investigator & Institution: Nunes, Edward V. Associate Professor of Clinical Psychiat; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 25-SEP-1999; Project End 31-AUG-2003 Summary: Depression is the most common comorbid psychiatric disorder in opiate dependent patients along with antisocial personality disorder. Depression has been associated with both severity of addiction and poor treatment outcome. This suggests that effective treatment of depression would improve outcome for opiate addicts. However, standard antidepressant medication trials in depressed methadone maintenance patients have yielded mixed results indicating that antidepressant
14 Methadone
medication treatment by itself is limited in this population. Several reasons for poor treatment response include: 1) poor compliance; 2) ongoing substance abuse; 3) ongoing stresses with which patients do not cope effectively; and 4) the absence of pleasurable, satisfying activities in patients' lives. A high rate of aversive circumstances and a low frequency of positive reinforcement are classic components in a behavioral model of depression. This suggests that a behavioral therapy could be an alternative or a complement to antidepressant medication treatment in this population. We propose a Stage I development project to design and pilot test a Behavioral Therapy for Depression in Drug Dependence (BTDD) that is based on behavioral model of depression. The primary goals of BTDD are to decrease depressive symptomatology by increasing the frequency of response-contingent positive reinforcement and to build a base of behaviors that can compete with illicit substance use. Aspects of three operant conditioning based treatment programs demonstrated to be effective for treating depression or reducing illicit substance use in other drug using populations will be incorporated in BTDD. These programs include: the Coping with Depression Course, the Community Reinforcement Approach and Treatment-plan contingency management. The latter techniques will be adapted so that reduction in depression is the primary goal. The specific aims over the four years of proposal are: 1. To develop a preliminary BTDD treatment manual through the treatment of 20 depressed methadone maintained patients in an uncontrolled trial. 2. To explore the efficacy and acceptability of BTDD with a randomized controlled pilot trial. 3. To test the theory that an increase in response-contingent reinforcement will produce an improvement in depression and reduced drug use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORALLY-CONTINGENT OPIOID DEPENDENCE
PHARMACOTHERAPY
FOR
Principal Investigator & Institution: Brooner, Robert K. Professor; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: An impressive number of studies have been conducted to improve the treatment response of patients receiving methadone substitution therapy. This work has become critically important because of the high rate of HIV transmission associated with drug abuse and the increasing number of patients responding poorly to standard methadone treatment. The trend toward poorer outcomes across methadone substitution programs parallels the epidemic of severe cocaine and other drug use problems in treatment seeking opioid abusers. Although studies now show that many forms of psychosocial treatments can enhance response to methadone pharmacotherapy, they also reveal limited interest and poor attendance when patients are offered these services. This problem illustrates the need for newer service delivery models that ensure participation in the psychosocial treatments necessary to maximize response to the pharmacotherapies. To be effective, these new models of treatment must also achieve success without doing harm to treatment retention. The approval of levo alpha acetyl methadol (LAAM) for opioid maintenance therapy raises yet another question that is important to evaluate- whether effective psychosocial treatments with one medication (i.e., methadone) will retain their efficacy across other pharmacotherapies. We previously demonstrated the effectiveness of a new treatment delivery model for opioid abusers that produced excellent clinical outcomes by making the continued availability of methadone ultimately contingent on counseling attendance and brief episodes of abstinence. In the proposed study, we will evaluate the efficacy of
Studies 15
this treatment in a new group of opioid abusers inducted and maintained on LAAM, which has a very different clinical medication reporting schedule that might interact with the behavioral interventions driving out treatment approach. A total of 220 patients will be randomly assigned to our specialized treatment or a standard care comparison group and evaluated over a 10 month period, including a month baseline and a three month follow-up. Major outcome measures include rates of counseling attendance, selfreported and objectively measured drug use, rates of HIV risk behavior change, and treatment retention. The study will also provide information about the influence of individual differences (e.g., psychiatric co- morbidity, personality, stages of change) on response to LAAM substitution when it is administered either contingently with, or independently of, scheduled counseling services. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BOMBESIN RECEPTORS MEDIATING METHADONE INDUCED APOPTOSIS Principal Investigator & Institution: Maneckjee, Rhoda; Surgery; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 08-JUL-1999; Project End 30-APR-2003 Summary: The therapeutic opioid drug methadone, that is generally used to treat cancer pain and opioid addiction, is also a potent inducer of apoptosis in human lung cancer cells, thus inhibiting their growth. This suggests a new therapeutic approach for the treatment of this cancer. However, in contrast to its central nervous system (CNS) actions, the apoptosis-inducing effects of methadone appear to be mediated through a non-opioid mechanism involving a dual- functioning bombesin receptor that is known to play a central role in the early events of pulmonary carcinogenesis. Methadone's effect is blocked in specific types of lung cancer cells that secrete high concentrations of bombesin and also by nicotine, suggesting the presence of an endogenous system coupling the apoptotic effects of nicotine, bombesin and opioids in these cells. This proposal aims to define the role of the bombesin receptor in this system, and determine whether distinct structural components are involved in the binding and functional coupling of the three ligands, with the aim of developing methadone ligands targeted towards tumor cells, and without CNS-associated toxic side effects. The specific aims of the proposal are (1) to identify the bombesin receptor type(s) involved in methadone's effects on the mitogen-activated protein (MAP) kinase signaling pathway, and apoptosis, using (a) Balb 3T3 cells transfected with the cloned bombesin receptor types (GRP, NMB and BRS-3), and (b) the different histologic types of lung cancer cells that differentially express these receptor types; (2) to determine whether nicotine actsthrough this receptor type(s) to block methadone's effects; (3) to identify the structural features of the bombesin receptor involved in methadone and nicotine actions, using synthetic peptides and site-directed mutagenesis; (4) to determine the role of guanine nucleotide-binding proteins in the observed differential regulation of the bombesin receptor by methadone and bombesin. A clinical trial of methadone therapy for lung cancer patients is in progress, and these studies are expected to contribute significantly to our understanding of methadone's actions at the molecular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRIEF MOTIVATIONAL HIV RISK REDUCTION AMONG IDUS Principal Investigator & Institution: Wells, Elizabeth A. Research Professor; Psychiatry and Behavioral Scis; University of Washington Seattle, WA 98195
16 Methadone
Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: Opiate users making initial contact with methadone treatment are at risk of injection-related and sexual transmission of HIV disease and are at higher risk if placed on a waiting list than it treatment availability was unlimited. The purpose of the project is to develop and test a theory- driven brief motivational intervention targeting injection-related and sexual risk behaviors for this population. Motivational Enhancement (ME) techniques (Miller & Rollnick, 1991) offer the advantages of brevity, feedback to clients that is specific to the cognitions and behaviors placing each person at risk, and use of the person's own ambivalence to motivate change. Elicitation research will be first be conducted via ethnographic interviews with 40 methadone waiting list clients to identify salient perceived consequences of risk behaviors, normative referents important to this population, and perceived facilitators of, and barriers to, behavior change. This information will be used to select and revise assessment tools to be used in a ME intervention. These tools will then be pretested with an additional 20 waiting list clients to determine whether they are readily understood, elicit a range of responses and can be used to give feedback to clients regarding their motivation and risk status. An ME intervention will then be tested in a randomized 1 X 3 partial repeated measures design in which 249 waiting list clients are assigned, 83 to ME, 83 to an AssessmentOnly (AO) group, and 83 to an Assessment-at-Follow-up- Only (AFO) group. Follow-up interviews will be conducted at 1 and 3 months and will include assessment of drug use, injection and sexual risk behaviors, intentions to engage in these behaviors, outcome beliefs and norms regarding these behaviors, stage of change, and self-efficacy to engage in protective behavior. It is hypothesized that the ME group will be less likely than the other two groups to engage in high risk sexual and injection behaviors at follow-up, will have beliefs and intentions less favorable to risk behavior, will have progressed in terms of stage of change related to risk behavior, and may, because of an increase in selfefficacy, be less likely than the other two groups to drop from the waiting list prior to treatment entry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPRENORPHINE ABUSE BY HUMANS--LABORATORY STUDIES Principal Investigator & Institution: Comer, Sandra D. Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: Heroin use and treatment admissions for heroin dependence have been increasing steadily. Clearly, there is a need for new effective treatments for opioid dependence. Buprenorphine, a long-lasting, partial agonist at the mu subtype of opioid receptor, is one of the most promising new maintenance medications for heroin dependence. Buprenorphine's advantages are that: (1) only mild withdrawal effects develop upon discontinuation of use; (2) it may retain its therapeutic effectiveness when administered on an alternate-day, rather than a daily, schedule; and (3) it is generally well-accepted by patients. Despite these advantages, research indicates that buprenorphine may have abuse liability. Although it is commonly believed that the abuse potential of buprenorphine is low, numerous countries have reported illicit diversion of buprenorphine and a growing population of buprenorphine abusers. To date, no laboratory studies have evaluated the abuse liability of buprenorphine in humans using a drug self- administration protocol, in which research volunteers are given the opportunity to take drug under controlled conditions. We are proposing to evaluate the abuse potential of buprenorphine in the laboratory, incorporating selfadministration procedures with other measures of opioid effects. Physiological
Studies 17
responses, subjects' verbal reports of drug effects, and learning and performance of a variety of computer tasks will also be measured. The studies will investigate the conditions under which buprenorphine may be self-administered in non- opioiddependent individuals with a history of opioid abuse, as well as in opioid individuals. The aims of the proposed studies are to: (1) determine the conditions under which buprenorphine will serve as a reinforcer; (2) evaluate the abuse liability of the buprenorphine/naloxone combination, which is currently being developed to reduce illicit diversion of buprenorphine; (3) compare the reinforcing effects of buprenorphine with methadone, which is currently the most widely used maintenance medication for heroin dependence; and (4) assess buprenorphine self- administration in participants maintained on different doses of morphine. This research will furnish useful information for clinicians treating heroin abusers, and importantly, will provide information about the effects of buprenorphine on multiple measures of human functioning, as well as actual buprenorphine use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPRENORPHINE MICROCAPSULES FOR HEROIN ADDICTION Principal Investigator & Institution: Nuwayser, Elie S.; Biotek, Inc. 21-C Olympia Ave Woburn, MA 01801 Timing: Fiscal Year 2002; Project Start 05-APR-2002; Project End 31-OCT-2003 Summary: (provided by applicant): The overall objective of the program is to develop a new more economical sustained action injectable formulation of -buprenorphine, based on microcapsules prepared by BIOTEK's air suspension process. The microcapsules will be used in a large placebo controlled study in Phase II of the SBIR program. Recently we tested 30-day buprenorphine microcapsules in five (5) heroin addicts at the Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit. For all five subjects the depot buprenorphine medication appeared to provide remarkable relief from opioid withdrawal without evidence of intoxication or respiratory depression over the six weeks of post-depot observation and assessment. Furthermore, the formulation was very effective in dramatically reducing responsiveness to exogenous opioid challenge for a duration of at least several weeks. Clinically, all five participants successfully achieved opioid detoxification, without other medications for withdrawal relief, and without clinically significant withdrawal signs or symptoms. During the subsequent 2-week outpatient phase all patients reported abstinence from opioids and urine toxicology samples were negative for opioids. These remarkable and very exciting findings compel us to drive forward and expand and accelerate the testing of depot buprenorphine in a large population of heroin addicts with appropriate placebo controls. Support is sought under the SBIR program to develop and optimize a more economic formulation of depot buprenorphine microcapsules, by using a new process which produces a much higher yield (5-6 fold increase) of microcapsules in the injectable size range. In preliminary studies detailed in this application, we have demonstrated significant reduction in manufacturing costs and the equivalency of the buprenorphine release profile from the old and new formulation. During Phase II of the SBIR program, microcapsule development will be completed, a large number of vials will be prepared under cGMP. The current IND will be updated and submitted to the FDA with a clinical protocol to test the formulation in a larger population of heroin addicts with appropriate placebo controls. PROPOSED COMMERCIAL APPLICATION: A sustained action opioid agonist/antagonist formulation, such as microencapsulated buprenorphine would be a significant advance. Once a month treatment is an economic advantage and allows staff members to devote more time to patients and less to dose
18 Methadone
administration. This formulation will provide opioid antagonism like that of naltrexone, but there would be less motivation for the post addict to drop out of therapy due to the agonistic action similar to that of methadone or LAAM. The overall treatment plan would not need to revolve about a rigid dosing schedule. Rather treatment could be designed to best benefit the patient, and an example of habitual drug taking behavior is eliminated. The drug thus becomes an adjunct not the major aspect of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANNABINOID ABUSE EFFECTS ON LEARNING AND MEMORY Principal Investigator & Institution: Moerschbaecher, Joseph; Vice-Chancellor for Academic Affairs; Pharmacology; Louisiana State Univ Hsc New Orleans New Orleans, LA 70112 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: (Applicant's Abstract) The overall objective of the proposed research is to characterize the effects of cannabinoids on complex, discrimination tasks involving learning and memory in nonhuman primates. A repeated acquisition and delayed performance procedure will be used to assess the effects of cannabinoids on memory in monkeys. These studies will enhance our understanding of how the cannabinoids affect complex behavioral processes and cognition. The first series of proposed studies are specifically aimed at continuing and extending our studies of the effects of various cannabinoid agonists and antagonists on the acquisition and performance of discriminations in monkeys. Specifically, acute dose-effect curves for the agonists 69THC, CP55,940, cannabidiol, and R-methanandamide and the antagonist SR141716A will be determined. Each agonist will then be tested in combination with BR141716A in order to characterize the nature of the antagonism. These studies are designed to test the hypothesis that the cannabinoid receptor system plays a role in modulating cognitive processes involved in learning. The second series of studies will characterize the acute effects of these same cannabinoid agonists on memory in monkeys. Specifically, these studies will evaluate the amnestic effects of these drugs and their actions on storage and retrieval processes following both short and long delays. These studies are designed to test the hypothesis that the cannabinoid receptor system plays a role in modulating cognitive processes involved in memory. Because polydrug abuse continues to be a major health-care problem, the third series of studies involves the acute characterization of cannabinoids in combination with other prototypical drugs of abuse. Specifically, cannabinoid ligands will be investigated in combination with opioids (heroin, methadone & buprenorphine), stimulants (cocaine, amphetamine & nicotine), and sedative-hypnotics (lorazepam 8 pentobarbital). These studies are designed to test the hypothesis that the effects of the cannabinoids on learning and memory are potentiated by other drugs of abuse. Together these studies will provide new information that will be of direct relevance to the clinical management of the cannabinoid user. In addition, studies involving the actions of the cannabinoid receptor antagonist alone will provide valuable data concerning the potential use of this and related agents in the pharmacotherapy of cannabinoid abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CENTER FOR EDUCATION AND RESEARCH ON THERAPEUTICS Principal Investigator & Institution: Woosley, Raymond L. Professor of Pharmacology and Medicine; Medicine; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 29-SEP-2007
Studies 19
Summary: (PROVIDED BY APPLICANT):During the initial three years of the Georgetown CERT (GUCERT) the program studied adverse drug interactions (ADIs), particularly those that result in drug-induced cardiac arrhythmias for which women are at increased risk. These original studies have identified new potentially lethal interactions and fostered awareness of ADIs across a wide array of drug classes. Healthcare providers have been unable to prevent ADIs in practice and we have found that curricula of medical schools and medicine residencies contain little information to prepare them to prescribe in ways that avoids harm from ADIs. GUCERT has developed curricula and aides to instruct providers on the range of potential ADIs, and is currently implementing and evaluating these educational programs. With the move to the Arizona Health Sciences Center, the new AzCERT continues the study of drug-drug interactions that result in arrhythmias. The web-based registry, www.QTdrugs.org, continues as the mechanism for initiating these studies. A major finding with life-saving potential is the observation that methadone can induce lethal ventricular arrhythmias. Mechanistic studies performed by AzCERT investigators now make it possible to test preventive measures. Newly proposed projects in this application will include a clinical study of the predictors of methadone-induced QT prolongation. The transition of the GUCERT to the AzCERT creates opportunities to expand the definition and scope of our research and convey this knowledge to healthcare providers and consumers in the multicultural context of the southwest. Our knowledge of the potential contributing factors for ADIs is expanding dramatically and this poses a substantial challenge for all healthcare providers. Our experience during the initial three years has shown that drug interactions must be approached on multiple fronts. We now fully recognize that drug interactions can occur due to systemic failures in which consumers and multiple providers are independently managing therapeutics. Substitution of prescribed drugs, addition of non-prescription, herbal or neutraceutical therapies, and modification of dosing regimens by patients are common. The risk of adverse outcomes grows when providers and consumers do not openly communicate and share in the management of therapies. AzCERT will employ laboratory, clinical and health services research using our broader systemic definition of drug interactions. The entire healthcare delivery system will be examined for weaknesses and potential improvements that are designed to prevent drug-drug and drug-herbal ADIs. Of equal importance, AzCERT will address the provider-consumer dialogue and develop health communication models to minimize risks from these more broadly defined ADIs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF TOXICITY WITH SPINAL OPIATES Principal Investigator & Institution: Yaksh, Tony L. Professor; Anesthesiology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Continuous intrathecal infusion of concentrated morphine is widely used in pain therapy. Surprisingly, until recently there has been no study of the safety of such infusions. We investigated the effects of 28-day intrathecal morphine infusion in a canine model. Unexpectedly, at high morphine concentrations (as used in humans), we noted an aseptic mass of inflammatory cells (granuloma) arising from the dura-arachnoid, not the parenchyma, proximal to the catheter tip. Granulomas were not seen with vehicle or a variety of non-opioid agents. The alpha2 adrenergic agonist clonidine suppressed the granuloma. These observations lead to four hypotheses. 1. Granuloma induction by morphine is proportional to local concentration in cerebrospinal fluid and not simply total dose. 2: Effect is mediated by an opioid
20 Methadone
agonist action and is not limited to morphine. 3. The granuloma results from a local degranulation of dural mast cells leading to movement of inflammatory cells from the dural vessels. Accordingly, granuloma-inducing potency will be proportional to the ability to degranulate dural mast cells in ex vivo dural preparations. 4. Granulomainducing effects and dural mast cell activation are suppressed by local alpha2 receptor agonists and by a mast cell stabilizer. We will address these hypotheses using the canine model to examine the effects of continuous intrathecal infusion of equipotent doses of mu opioid agonists (morphine, morphine-6-glucuronide, L-methadone, hydromorphone, fentanyl or DAMGO) or equimolar concentrations of inactive opioid molecules (naloxone, morphine-3-glucronidc, D-methadone). In vivo treatment with a mast cell stabilizer, nedocromil sodium, will be examined for its effect on granuloma formation. In parallel studies, kinetics studies will permit comparisons based on measured CSF concentrations. Interaction between morphine and alpha2 agonists (clonidine, dexmedetomidine) will be studied by co-delivery. Granuloma formation and local mast cell degranulation and cytokines will be assessed histochemically and by CSF analysis. In summary, our initial work, provides the first definitive preclinieal data defining the effect, the attenuation by clonidine, and a novel mechanistic hypothesis for drug-induced degranulation of dural mast cells which suggests a novel method for the ex vivo screening of new agents. These studies are significant: 1) increasing incidence of reports of morphine-granulomas emphasize it is not rare; 2) our investigation of other opioids provide the first time assessment of the spinal safety of agents which are now in wide clinical use; and 3) this issue impacts on all agents targeted for intrathecal delivery. Accordingly, data obtained here regarding the role of local CSF concentration, the safety of non-morphine agents and the potential ameliorating effects of adjuvant agents all provide novel information to refine the utility of this important therapeutic regime. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS Principal Investigator & Institution: Kozikowski, Alan P. Professor and Head; Neurology; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 31-MAY-2005 Summary: (Applicant's Abstract) Immediate therapies are needed for the treatment of cocaine abuse worldwide. At present, there are no effective medications available to treat cocaine addiction. In order to develop agents that might find use in the treatment of cocaine abuse, the search for both cocaine antagonists and partial agonists is being pursued. While antagonists are more likely to find use in situations of cocaine overdose, the substitute agonist approach may prove more useful in maintenance programs. Compounds that possess the ability to mimic partially the effects of cocaine may help to maintain individuals in treatment programs while slowly withdrawing them from cocaine. Basically, what may be needed for cocaine abuse treatment is the pharmacological equivalent of a methadone, a drug widely used in the treatment of opiate abuse? In continuation of our past efforts to explore the structure-activity relationships of tropane analogs, we will continue to screen new compounds for their possible antagonist action. Additionally, in pursuit of a methadone type of approach, we intend to identify one or more tropanes that exhibit partial cocaine-like properties in vivo, and, specifically, substances that may elicit some of the same effects in the user as cocaine itself, but without causing the same degree of euphoria. As it is difficult to precisely define the pharmacological characteristics of transporter targeted ligands that may ultimately prove useful as cocaine medications, we believe it is essential to examine
Studies 21
behaviorally a range of ligands showing varying degrees of DAT, NET, and 5-HTT activity, with the aim to identify the selectivity profile(s) that may be optimal for cocaine medication development. To date we have constructed a rich array of ligands that encompass elements of both structural diversity as well as varying levels of transporter inhibitory activity. 7 (1) For some of the classes of ligands already synthesized, further refine their transporter selectivity profiles through additional SAR studies; construct several new ligand classes including dimeric structures and GABA-mimetic/transporter conjugates; (2) Characterize pharmacologically all compounds by studying their ability to inhibit WIN35,428 binding, DA, NE, and 5-HT uptake using rat synaptosomal preparations; (3) Scale up selected compounds for animal behavioral studies to -be conducted by the Medications Development Division of NIDA; the compounds to be scaled up will be selected based upon their transporter affinities and selectivies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC MORPHINE: REGULATION OF ION CONDUCTANCES Principal Investigator & Institution: Williams, John T. Senior Scientist; None; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2002; Project Start 01-APR-1993; Project End 31-JUL-2007 Summary: Chronic use of morphine results in tolerance to and dependence on the drug. One mechanism underlying cellular tolerance is an uncoupling of the opioid receptor from effects such that greater receptor occupancy is required to obtain a given response. This uncoupling mechanism has been studied using effectors that include; potassium and calcium conductances and the inhibition of adenylyl cyclase. A similar phenomenon is observed with acute opioid desensitization. Acute desensitization is thought to involve at least two linked processes, receptor uncoupling through an arresting dependent mechanism and removal of receptors from the plasma membrane through an internalization mechanism. Unlike more protracted forms of tolerance, acute desensitization is reversible within minutes and therefore easier to study in vitro. One goal of this proposal is to define the events that mediate the initiation and recovery from acute opioid desensitization. This goal has two parts, one is to characterize acute desensitization and determine the role of receptor internalization in that process. Given that receptor trafficking is an important form of receptor regulation, the second goal is to characterize how chronic morphine treatment alters desensitization and internalization of the opioid receptor. With a better understanding of the events that mediate desensitization and internalization the processes leading to long term tolerance may be more easily identified. The second goal is to identify post-synaptic cellular adaptations to chronic opioid treatment. These adaptations oppose the initial effect of opioid such that normal function is attained even in the continued presence of morphine. Thus adaptive mechanisms underlie an important form of tolerance. Two cell types will be examined the neurons in the locus coeruleus and interneurons of the VTA. There is an extensive knowledge of opioid actions in these areas, however, the identification and characterization of a post-synaptic adaptive mechanism studied in isolation has yet to be presented. Knowledge of alterations in regulation of ion channels during withdrawal form morphine may help in the development of more efficient protocols for the prevention of relapse to drug use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
22 Methadone
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Project Title: CHRONIC OPIOID SELF ADMINISTRATION IN THE PRESENCE OF NEUROPATHIC PAIN Principal Investigator & Institution: Martin, Thomas J. Associate Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, NC 27106 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Extensive study of opioids has generated much information regarding the mechanisms of their analgesic and reinforcing properties. Distinct anatomical pathways have been elucidated for the antinociceptive and reinforcing properties of opioids using antagonists and neurotoxin- induced lesions of specific neuronal populations. However, these two important aspects of opioid pharmacology have largely been studied in isolation. The analgesic effects of opioids are studied in the laboratory following passive administration, in which the animal does not control the dose or dosing interval. Similarly, the reinforcing effects of opiates are studied in the laboratory in the absence of pain, and little is known regarding the relevance of reinforcing mechanisms identified in this manner to the clinical use of opioids for pain relief. This project seeks to examine the pharmacology of opioids using a self-medication paradigm in rats with nerve injury. These studies will focus on the development of opioid tolerance in the presence of pain and exploration of the mechanisms of tolerance. Dosing will be accomplished through self-administration, in which the animal is allowed to determine the drug quantity necessary to achieve the desirable pharmacological effect. This technique has proven to be invaluable in the study of drug abuse, but is being applied in this project to the study of pain mechanisms and should provide equally invaluable information. Experiments are designed to determine receptor mechanisms related to the development of tolerance as well as to develop strategies for minimizing the development of tolerance and selfdetermined dose escalation through experiments using 24 hr self-administration. Preliminary data show that animals rapidly escalate opioid intake when given 24 hr access to self-administration, and that tolerance to the anti-allodynic effects of opioids results. Initial strategies include using drugs of differing efficacies and a dose-fading procedure to determine the optimum maintenance dose that minimized total dose escalation over time. Intrathecal agents will then be given as adjuvant analgesics as another strategy to inhibit or retard the development of tolerance to opioids and subsequent dose escalation. Parallel clinical studies are proposed to address these concerns in patients self-administering opioids. These studies will hopefully identify mechanisms of tolerance to opioids self- administered for pain relief and strategies to minimize such effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLIENT AND COUNSELOR ATTITUDES TOWARD MEDICATION Principal Investigator & Institution: Mccarty, Dennis; Professor; Public Health and Prev Med; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: Progress in the development of medications for the treatment of drug dependence will lead to little adoption if practioners and patients are not ready, willing and able to embrace medication technologies. Reports that clients and counselors resist the use of pharmacotherapy for drug abuse treatment suggest that attitudes and beliefs may be a substantial barrier to diffusion and adoptions. It is critical, therefore, to systematically investigate the cognitive determinants (attitudes, beliefs, norms, and intentions) of behaviors related to the use and non-use of medication. Four inter-related investigations are proposed to explore the attitudes, beliefs and social norms that
Studies 23
contribute to intentions to use medications. The Theory of Reasoned Action (Ajzen, 1985; Ajzen &Fishbein, 1980; Fishbein & Ajzen, 1975) provides a theoretical framework for the assessment and guides the development of persuasion messages. Four medications are examined: methadone, buprenorphine, clonidine and ibogaine. The proposal has four aims: Aim 1. Identify the most salient beliefs related to the use of medications among clients and counselors in outpatient, methadone, and residential treatment programs and develop and instrument to assess attitudes and beliefs. Aim 2. Assess clinical staff working in outpatient, methadone, and residential settings to determine the relative influence of attitudes and social norms on intentions to support clients use of medications for heroin treatment. Aim 3. Survey clients in outpatient, methadone, and residential settings to determine the relative influence of attitudes and social norms on intentions to use medications as part of a heroin treatment plan. Aim 4. Test the impact of persuasion messages on medication usage attitudes, beliefs, normative beliefs, and attentions among both clients and counselors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL INVESTIGATION OF DRUG ABUSE DISORDERS Principal Investigator & Institution: Brady, Kathleen T. Professor of Psychiatry; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: This mid-career investigator award application is designed to support the continued efforts of Dr. Kathleen T. Brady, M.D., Ph.D. in conducting and mentoring patient-oriented drug abuse research. Dr. Brady has been continuously funded to conduct patient-oriented research with substance abusing individuals since completing her psychiatric residency training in 1989. Her particular areas of interest are in psychiatric comorbidity with substance use disorders and the pharmacotherapy of substance use disorders. She is currently funded as the PI on four (Concurrent Treatment of PTSD and Cocaine Dependence, Naltrexone Use in a Community Setting, Sertraline Treatment of Comorbid Alcoholism and PTSD, and Valproate in Relapse Prevention) and the Co-PI on two (Amlodipine in Cocaine Dependence and Buspirone in Methadone Maintained Individuals with GAD) patient-oriented substance abuse research projects. Dr. Brady has a strong track record in mentoring beginning clinical researchers. She is currently the director of the Addiction Psychiatry Fellowship Program and the co-director of a NIDA-funded post-doctoral research fellowship training program. Dr. Brady is a faculty member in the Center for Drug and Alcohol Programs (CDAP) which is an active and productive clinical and research training environment. CDAP provides a variety of education and training-related activities to faculty and students. There are currently eleven faculty at CDAP conducting eighteen funded, patient oriented research projects. The candidate's immediate career goals include the initiation of pilot work to support the competing renewals of existing projects and assisting two junior faculty with the submission of K awards. Her longterm career goals are to continue work in patient-oriented substance abuse research in new directions which build on existing studies. Investigation of CRF antagonists in the treatment of substance use disorders in a clinical setting and the development of a human laboratory model for the measurement of risk-tasking and impulsivity are two areas of preliminary investigation which would be developed during the award period. The candidate would also use the time and funding provided through this award to expand her activities in mentoring fellows and junior faculty in patient-oriented research. This award will allow Dr. Brady to be relieved from a number of clinical and
24 Methadone
administrative duties in order to refocus her career to center on clinical research and clinical research training activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL TRIALS NETWORK: NEW MEXICO NODE Principal Investigator & Institution: Miller, William R. Distinguished Professor; Psychology; University of New Mexico Albuquerque Controller's Office Albuquerque, NM 87131 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The University of New Mexico Center on Alcoholism, Substance Abuse, and Addictions (CASAA) submits a revised application to join the NIDA Clinical Trials Network as a Regional Research and Training Center and coordinate a New Mexico Node. CASAA and the collaborating Department of Psychiatry of UNM's School of Medicine have well -established infrastructure for behavioral and pharmacotherapy trials, and long experience with collaborative and multisite trials in the addiction field. Particular strengths that the proposed New Mexico Node team can bring to the CTN include: 1) expertise in "Stage III" research on dissemination and training of evidence-based treatments 2) a well -established track record of clinical trials for both behavioral and pharmacotherapies 3) a high concentration (70%) of minority patients in the affiliated CTP's, and substantial experience in research on cultural influences on and adaptations of drug abuse treatment 4) longstanding experience in the development and evaluation of innovative treatment methods for substance use disorders 5) substantial clinical and research experience with challenging populations including dual disorders, the homeless, and runaway adolescents 6) expertise in studying the influence of mutual help (e.g., 12-step) programs on treatment outcomes, and more generally in research on spirituality and addictions 7) geographic representation of the border Southwest To illustrate CTN-wide research that could be initiated from the New Mexico node, protocol concepts for three clinical trials are described, encompassing a behavioral intervention, a pharmacotherapy, and methods for disseminating an evidence-based treatment into clinical practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLOZAPINE DRUG DISCRIMINATION IN C57BL/6J MICE Principal Investigator & Institution: Philibin, Scott Commonwealth University Richmond, VA 232980568
D.
Psychology;
Virginia
Timing: Fiscal Year 2003; Project Start 18-AUG-2003; Project End 17-AUG-2006 Summary: (provided by applicant): Clozapine is the prototypical atypical antipsychotic drug and represents a tremendous improvement over conventional antipsychotics in terms of therapeutic efficacy and reduced side effect liability for the treatment of schizophrenia. Understanding the pharmacological properties that are important for clozapine's unique profile can help lead to the discovery of improved and safer antipsychotic drugs for the treatment of schizophrenia. One approach for investigating the molecular bases underlying the relationship of pharmacological agents and behavior has been the use of gene-targeted knockout or transgenic animals. This technique allows for the manipulation of receptors for which selective pharmacological ligands do not exist. One restriction of this approach is that most of the knockout mutations that have been developed are available only in mice - not rats. Therefore, it is necessary to have preclinical assays for mice in order to utilize these new and potentially powerful new
Studies 25
techniques. The current proposal represents an important first step in this process. Twolever drug discrimination is a valuable preclinical behavioral model that has been used to investigate the discriminative stimulus properties of clozapine in rats and has helped identify neurotransmitter receptor targets for putative atypical antipsychotics. Wildtype mice (C57BL/6J) will be trained to discriminate clozapine from vehicle and then a series of atypical and typical antipsychotic drugs will be tested to determine which drugs generalize to clozapine's discriminative cue. Establishing this procedure in wildtype mice will allow for the future use of knockout and transgenic mice and will expand the tools available to molecular geneticists and behavioral pharmacologists. This will help to increase our understanding of the perplexing pharmacology of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCAINE VACCINE FOR METHADONE MAINTAINED PATIENTS Principal Investigator & Institution: Kosten, Thomas R. Professor of Psychiatry; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant) This 20 week, placebo-controlled randomized clinical trial among 120 methadone maintained cocaine abusing patients is designed to test the efficacy of a newly developed active vaccine against cocaine (TA-CD) in conjunction with cognitive behavioral therapy (CBT). This vaccine generates antibodies that can retain cocaine in the bloodstream and allow naturally occurring cholinesterases to convert cocaine into inactive metabolites. Previous work by this investigator has shown a dose (100ug) and regimen (4 injections over 8 weeks) among cocaine abusers is clinically safe and produces substantial levels of anti-cocaine antibodies that persist for at least 3 months after final vaccination. TA-CD is however limited by two factors: 1) antibodies take 6-8 weeks following multiple inoculations to rise to effective levels, and 2) although it reportedly attenuates the subjective effects of cocaine, it can be overridden by increasing cocaine doses. To address these limitations, methadone maintenance will retain patients while the vaccine becomes effective, and the CBT will encourage abstinence. Because initial cocaine abstinence carries a good prognosis and we hypothesize that TA-CD's optimal efficacy will be to maintain this abstinence, we will stratify patients on their ability to attain a week of abstinence during an initial 2week run-in period prior to randomization. Thus, during weeks 1-10 subjects will be maintained on methadone and learn the skills of CBT, at week 3 they will be randomized to vaccine or placebo and by week 10 complete the vaccine regimen of 4 injections over 8 weeks. Weeks 11-20 will provide clinical trial testing of the efficacy of TA-CD vs. placebo. Follow-ups at weeks 24, 28, & 32 will track any decline in antibody levels as well as cocaine use. To allow for analyses based on variation in antibody levels patients will be randomized in a 2 to 1 ratio of active to placebo (80 to 40 patients). Outcomes include treatment retention and 3 times per week urines for cocaine metabolites. Because the levels of antibody are expected to vary across individuals, antibody levels will be used as a covariate in analyses of outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMBINING BEHAVIORAL TREATMENTS WITH AGONIST MAINTENANCE Principal Investigator & Institution: Schottenfeld, Richard S. Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2003
26 Methadone
Summary: This is a competing renewal of our 2x2 study evaluating methadone vs. buprenorphine and the Community Reinforcement Approach (CRA) with and without Contingency Management (CM) for the treatment of patients with concurrent opioid and cocaine dependence. Data analyses showed significantly greater improvements for methadone vs. buprenorphine and limited efficacy of CM, with a rebound in drug use after the value of the vouchers was reduced to a nominal level. Limitations of CRA and CM with opiate agonist maintained patients identified in this and other studies include the low motivation of patients to address problems of cocaine use; difficulties implementing the multifaceted and complex treatment; and the limited efficacy of CM. Therefore, we are proposing a Stage I study for manual development and pilot testing of a behavioral and social-learning theory based treatment for agonist maintained patients with combined opioid and cocaine dependence that addresses several weaknesses of CRA and CM in this population. This treatment, referred to as Therapeutic Contracting (TC), combines core aspects of the Community Reinforcement Approach (CRA) associated with improved outcome in the current study and cognitive and social learning theory based techniques which can serve as alternatives to CM for enhancing patients motivation, overcoming demoralization, and improving goal achievement. In the proposed study, we plan first to refine TC and develop an individual therapy manual and training materials for it during pre-pilot testing in 10 methadone maintained patients with combined opioid and cocaine dependence. During the prepilot, we also plan to develop TC adherence and competence rating scales. Subsequently, we plan to conduct a pilot study using a dismantling design to compare TC and one of its components, manual-guided cognitive-behavioral coping skills therapy (CBT). For the pilot, 3-5 therapists will be trained to administer each of the treatments and patients will be randomly assigned to 24 weeks of either TC or CBT. Primary outcome measures include reductions in illicit opioid and cocaine use and achievement of abstinence from them, as assessed by three times per week urine toxicology tests and self-report. The pilot study will be used to estimate the potential effect size of the difference between these two treatments and to evaluate the feasibility of comparing TC and CBT in a larger Stage II study. Feasibility will be evaluated by assessing whether therapists can be trained to adhere to the manuals and administer the treatments competently; whether patients can be retained in the treatments; and whether the treatments can be reliably discriminated by raters blinded to treatment assignment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMMUNITY BASED INTERVENTION AT NEEDLE EXCHANGE SITES Principal Investigator & Institution: Kidorf, Michael S. Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-AUG-2002 Summary: Needle exchange programs were designed to provide injection drug users with ready access to sterile needles and syringes to reduce the frequency of sharing contaminated equipment and thereby lower the risk of transmitting HIV and other blood borne diseases. Most programs also counsel participants against continued drug use and offer drug abuse treatment referrals to those who request one, but only a minority actually pursue referral into treatment. The proposed 3-year study will systematically evaluate a promising community-based intervention for encouraging opiate abusers to enroll in treatment. New registrants at the Baltimore City Needle Exchange Program (n=1011) will be first assessed for rates of substance use and other
Studies 27
psychiatric diagnoses, severity of substance use and psychosocial problems, and HIV drug use and sexual risk severity. Those who are methadone eligible (n=807) will be randomly assigned to one of three treatment referral strategies: 1) self-referral (SR),2) motivational enhancement (ME), and 3) attention control (AC). SR participants will contact routine needle exchange staff on their own about any interest in a treatment referral; this strategy is the usual procedure. ME participants will be administered a structured motivational interview highlighting the benefits and consequences of treatment participation (Miller and Rollnick, 1991) and then asked to indicate their interest in a referral to treatment. An attention control referral group (AC) will control for time spent with ME participants by engaging participants in a job readiness interview and then asking if they are interested in a treatment referral. All participants requesting drug abuse treatment will move to a treatment referral action phase enroute to admission to non-methadone (if requested) or methadone treatment slots dedicated to the needle exchange program (n=250). The primary dependent measures are: 1) proportion of participants in each condition who request a treatment referral; 2) proportion of participants who enter treatment. All study participants will be followed for 10-16 months (depending on if and when they entered treatment) following registration to determine use of the exchange program (i.e., number of days attended and syringe exchanges); retention rates will also be determined in those who enter treatment. The proposed study will provide new and important information on the problem characteristics of new needle exchange enrollees. This data will also be used to predict response to the referral interventions. The motivational intervention evaluated in this study is a logical next step to strengthen the impressive public health benefits already achieved by most needle exchange programs. Importantly, this intervention can be easily incorporated as routine practice in most exchange programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPRENHENSIVE EMPLOYMENT PROGRAM FOR METHADONE PATIENTS Principal Investigator & Institution: Coviello, Donna M. Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant) While some methadone treatment programs have found success in motivating patients to obtain employment, the next challenge is to design integrative programs to show improvements in job functioning and sustain patients in long-term employment. Pilot work at our Center has shown the importance of integrating drug and employment counseling. Training methadone counselors to deliver the intervention allows clinics to be reimbursed for services and patients to have ongoing long-term support from a trusted member of their recovery team. The proposed intervention is comprised of three components including: 1) standard methadone counseling techniques that evaluates patients' performance in treatment, 2) integrated drug and employment counseling based on interpersonal cognitive problem solving (ICPS), and 3) the provision of integrative ICPS maintenance counseling to help sustain employment. ICPS drug counseling is integrated with the ICPS employment counseling through the use of a decision-making protocol that systematically assesses patients' needs during each counseling session. We propose to conduct an integrative Stage I A/B study under the behavioral therapies development program with the following objectives: 1) develop a training manual that incorporates methadone maintenance counseling and employment services, 2) train four MMT counselors to deliver the intervention and then monitor and evaluate their performance, and 3) conduct a pilot
28 Methadone
study with 48 methadone patients randomized to either this integrative ICPS counseling intervention or to ICPS drug counseling alone (control condition). We hypothesize that integrative ICPS patients will be more likely controls to: 1) be working at the end of the 26 week intervention, 2) be working at the 12 month follow-up, 3) sustain employment at the 12 month follow-up if employed at 6 months, 4) obtain a job more quickly and keep it longer, 5) show improvements in self-reported substance use and social functioning (e.g., family, legal), and 6) have cleaner urines throughout the intervention. Thus, we will evaluate whether this comprehensive intervention is effective in assisting methadone patients in obtaining work, reducing drug use, improving social functioning and sustaining patients in long-term employment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT
CONTINGENCY
MANAGEMENT
FOR
REAL-LIFE
DRUG
Principal Investigator & Institution: Amass, Leslie; Principal Investigator; Friends Research Institute, Inc. Box 10676, 505 Baltimore Ave Baltimore, MD 21285 Timing: Fiscal Year 2001; Project Start 25-MAY-2000; Project End 30-APR-2005 Summary: Despite research demonstrating the efficacy and patient acceptability of voucher-based contingency management (CM) interventions for reducing drug use, community providers have been slow to adopt these procedures. One barrier to adoption of CM procedures is the high cost of supporting such programs. However, novel approaches using community- or user-supported services to reinforce drug abstinence or other target behaviors may offer a solution for financing CM programs. The specific aims of this proposal are to evaluate Contingent Fee Rebates and a Community-Sponsored Voucher Program, two innovative and potentially cost-effective CM strategies for use in community-based drug treatment programs. This project's goal is to make the robust success revealed by voucher-based contingency-management research practical enough for widespread testing and adoption by community-based practitioners. These strategies will be examined in three publicly-funded clinics within a large, urban, outpatient substance abuse service in Denver, CO. Four controlled studies will evaluate the use of these techniques with a range of substance abusers, including dually-diagnosed, pregnant, HIV-positive populations and children to increase the generality of our findings. Studies 1-3 will provide an examination of Contingent Fee Rebates for improving treatment outcomes among methadone-and LAAM-maintained outpatients. Study 4 will evaluate a community-sponsored voucher program for reducing smoking and other drug use among pregnant substance abusers using an incentive store stocked by community and manufacturer donations. Establishing a community-sponsored voucher program reinforces the role of the community in substance abuse treatment. The proposed research will use different CM strategies to elucidate the most practical and effective reinforcement schedules (fixed vs. variable) and the optimal target behaviors to reinforce (drug use vs. counseling attendance). Studies will be integrated into the existing structure of clinical programs to demonstrate the feasibility of transferring the CM procedures to existing community-based programing. Behavioral interventions will be delivered in conjunction with pharmacological adjuncts available at each site. The impact of our interventions on reducing AIDS risk behaviors will also be assessed. Finally, throughout the five years of this proposal, we will train new practitioners in the use of these strategies and work with NIDA to create training materials such as manuals, software, videos and detailed fundraising strategies for dissemination to clinicians and policy makers. Overall, these studies will guide practitioners in the use of CM for real-life drug abuse treatment.
Studies 29
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTINUITY OF CARE FOR DRUG-ADDICTED OFFENDERS IN RI Principal Investigator & Institution: Friedmann, Peter D. Associate Professor; Rhode Island Hospital (Providence, Ri) Providence, RI 02903 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This cooperative agreement application proposes to develop a Rhode Island Research Center to participate in NIDA's National Criminal Justice Drug Abuse Treatment Services Research System (CJ-DATS). The mission behind the CJ-DATS is to improve the public safety, drug-related, public health, health and psychosocial outcomes of drug-involved offenders. Thus, this application aims to develop research infrastructure to support rigorous, multisite studies of integrated approaches to the treatment of individuals with drug abuse or addictive disorders, including models of treatment in jail or prison and as part of community re-entry; to support research on continuity of care models integrated with re-entry programs for drug-involved offenders returning to their communities, including services for health problems such as HIV, tuberculosis, or hepatitis infections and mental health problems; and to enrich the collaborations among the criminal justice, treatment, and academic communities in Rhode Island. Our Research Center will build on the strong, existing clinical and research partnerships among the Lifespan Hospitals/Brown University investigators, the Department of Corrections and 4 community addiction treatment programs already situated in the Rhode Island prison. These 4 programs deliver a comprehensive range of treatment modalities and ancillary services. The Rhode Island Research Center offers at least 4 specific advantages to the National CJ-DATS Cooperative: (1) Investigators and treatment partners with substantial research and clinical experience regarding the organization and integration of substance abuse treatment and health services, especially continuity of care models for community reentry of inmates afflicted with health problems such as HIV, tuberculosis, or hepatitis infections, and mental health disorders; (2) Strong, existing ties among the Rhode Island partners from prior collaborative research and clinical endeavors; (3) A small state with a unified correctional system, all divisions and facilities on a single campus and an administration highly supportive of research; and (4) An accessible population of addicted persons in which we have achieved high rates of enrollment and follow-up in prior investigations. The Rhode Island Research Center would lead rigorous multisite studies that draw on our expertise in the development, delivery and evaluation of linkages to community health services, with an initial focus on hepatitis C and methadone treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--CLINICAL RESEARCH Principal Investigator & Institution: Bart, Gavin;; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: CORE ABSTRACT NOT PROVIDED Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COST AND ADHERENCE IN DRUG ABUSE TREATMENT Principal Investigator & Institution: Stoller, Kenneth B. Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218
30 Methadone
Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This is a proposal for a Mentored Patient-Oriented Research Career Development Award (K23). A team of highly accomplished and diverse mentors, all full professors at Johns Hopkins, has committed to support the proposed work to facilitate my transition to an independent patient-oriented drug abuse treatment researcher. Their records of productive research and experience in mentoring junior faculty are extensive and their respective areas of expertise are complementary and central to the content of this proposal (involving drug abuse treatment, cost/cost-benefit analysis, and adherence to treatment services). Dr. Eric Strain is a psychiatrist highly recognized for his research involving clinical pharmacology and drug abuse treatmentevaluation. Dr. Robert Brooner is a widely respected clinician and researcher with particular interest in novel treatment models utilizing behavioral enhancements. Dr. David Salkever is a highly recognized leader on the cost/cost-benefits of medical care. This proposal consist of three highly related components of my career development plan which will be enabled by this award: 1) enhance my knowledge and expertise in medical economics, cost/cost-benefit methodologies, general clinical trials methodology and analyses; 2) design, conduct, analyses and publication of the results of four studies involving cost and cost benefit of varying treatment models and interventions and on improving adherence to drug abuse treatment plans; and 3) use of this experience and data to inform the development and submission of future R01 or similar grant mechanisms to extend my work in these areas. The joint focus on the cost/cost-benefits of treatment and adherence to treatment services springs from their interdependence. For example, poor adherence effectively increases the cost of services actually delivered to patients in a treatment program, while good adherence can reduce those costs. My proposed research will therefore evaluate the cost and cost-benefit of drug abuse treatment services and both interventions and service models designed to improve patient adherence. It is hypothesized that significant interactions exist between drug abuse treatment interventions, patient adherence and treatment outcome and cost. This work will require completion of a series of academic courses on medical economics, cost-effectiveness and cost-benefit analyses and the completion of four studies. The first two studies evaluate cost and cost-benefit of a novel Motivated Stepped Care (MSC) treatment system for patients receiving either methadone or LAAM. The third study compares treatment costs and cost-benefit for combinations of MSC and voucher-based incentive to reduce drug use. The fourth study examines the effectiveness of a "significant other" intervention in improving rates of follow-up care after discharge from an inpatient unit. The results of this work will be used to inform the development of a new R01 type application to extend my work to a series of controlled evaluations of services and service models to improve patient adherence and maximize the cost effectiveness of treatment services. This accomplishment will document my transition to the status of an independent patient-oriented researcher and recognized expert in the field of drug abuse treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEFINING FATHERHOOD AMONG DRUG DEPENDENT MEN Principal Investigator & Institution: Witte, Susan S. None; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): The proposed R03 (PA 99-113) is designed to examine parenting attitudes and behaviors among African American and Latino fathers attending methadone maintenance treatment programs (MMTPs), and to explore how
Studies 31
parenting attitudes and behaviors are affected by a father's current and past experiences with drug use and intimate partner violence (IPV). Substance use and parenting literature indicate that drug use compromises positive fathering and can constitute barriers to healthy father-child relationships. In addition, studies on IPV have revealed a significant problem among men being treated for drug abuse, and an overlap of IPV and child abuse occurring in families. However, to date, surprisingly few efforts have been made to study the role of fathers in violent families and no studies have examined how fathering attitudes and behaviors are affected by IPV among drug-dependent men. Concurrently, there is substantial and growing evidence suggesting that fathers have positive influences on their children, and that fathering may have positive effects on the well being of men in general. In light of research indicating that positive father effects may be countered by IPV and child abuse, promoting positive father-child relationships among violent men is extremely complex. Building on findings generated from ongoing NIDA studies, and guided by social learning theory and an ecological framework, the study will collect contextual narratives on the experience of fatherhood among 72 African American and Latino men in a New York City-based MMTP through focus groups and in-depth interviews. Through a contextually rich, in-depth understanding of the complex dynamics of these relationships afforded through qualitative inquiry, we aim to further inform and enhance paternal support interventions and services to promote healthy father-child involvement. The findings will also inform an R01 application aimed at the development and efficacy testing (using quantitative methods) of a parenting support intervention provided in drug treatment settings for a random sample of drug-dependent fathers and their families. Dr. Susan Witte will conduct the study under the guidance of Dr. Nabila EI-Bassel of the Social Intervention Group (SIG) at the Columbia University School of Social Work, and in consultation with Drs. Suniya Luthar and Peter Steinglass. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETERMINANTS OF DRUG EFFECTS ON DRUG MAINTAINED BEHAVIOR Principal Investigator & Institution: Goeders, Nicholas E. Professor; Pharmacology and Therapeutics; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, LA 71103 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 31-MAY-2003 Summary: (Adapted From The Applicant's Abstract): Substance abuse is a serious threat to society for which effective therapies are sought. Since no single effective treatment for substance abuse has been identified, current strategies seek to combine behavioral and pharmacological therapies. Successful pharmaceutical therapies include the agonistbased maintenance therapies: methadone (for heroin abuse) and nicotine patches (for tobacco abuse). Despite a profound understanding of the pharmacological actions of these drugs, the basis for their therapeutic effects remain unclear. In addition, no effective treatment has been found for cocaine abuse. Behavioral data from animal models may improve methods for developing these medications. Drugs that can decrease drug self-administration without having effects on other behaviors may be potential candidates. We recently developed a promising series of findings on the treatment of cocaine-maintained responding with the selective dopamine (DA) reuptake inhibitor GBR 12909. Acute administration abolished cocaine-maintained responding, while having no effect on food-maintained responding. Repeated administration sustained this effect, and a single injection of a long-acting decanoate formulation decreased cocaine-maintained responding for almost thirty days, while having little or
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no effect on food-maintained responding. While the behavioral effects of GBR 12909 and its decanoate appear very promising, their physiological effects may warrant further study. For example, cocaine has cardiovascular effects, and the potential of these drugs for interaction with this effect should be explored. Lastly, the effects of agonist-based treatments are likely to depend upon both specific pharmacological actions and behavioral factors. Our collaborators continue to modify the GBR series to improve its pharmacology and we also propose testing additional drugs as potential adjuvants to improve the effects of GBR analogs. The specific aims of this grant are to 1) further evaluate the effects of an ultra long-acting formulation of GBR 12909 alone and in combination with other drugs, 2) assess the behavioral effects of novel GBR 12909 analogs, with the aim of identifying improved decanoate candidates, and 3) assess the effects of GBR 12909 analogs and GBR 12909 decanoate alone, and in combination with cocaine, on cardiovascular functioning. These studies are designed to extend the agonist-based approach to the development of potential medications for the treatment of cocaine abuse and further our understanding of the behavioral pharmacology of the self-administration of cocaine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF THE SURVEY OF TREATMENT ENTRY PRESSURES (STEP) Principal Investigator & Institution: Marlowe, Doug;; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001 Summary: Current motivational assessment instruments measure clients' attributions about their readiness to change problem behaviors. Motivation for change is typically characterized as a uni-dimensional construct, represented either by a single summative score, or by a profile of scores on scales that are believed to measure a progressive sequence of motivational stages. Although yielding important information, these data do not indicate why a particular client may be motivated for treatment, nor do they suggest how the treatment provider might maintain or improve upon the client's motivational state. Presumably, readiness to change is precipitated by specific events or pressures that impinge on a client as a result of substance abuse. These pressures may be characterized along dimensions (i.e., "negative" vs. "positive," "internal" vs. "external""), and they emanate from various biopsychosocial domains (e.g., legal, familial, financial, medical). A multi-dimensional assessment of these treatment- entry pressures would yield important information about a client's motivational state, and might suggest specific strategies for engaging and retaining the client in treatment. We defined the content domain of treatment-entry pressures by interviewing over 500 clients in diverse substance abuse treatment programs about their reasons for entering treatment. We performed a systematic content analysis of subjects' interview responses, and used these response to devise items for a standardized instrument, the "Survey of Treatment-Entry Pressures" (STEP). An expert panel on test construction reviewed the items for clarity and placed them into preliminary scales according to our clearly articulated theory about the important dimensions of treatment-entry pressures. The goals of the proposed studies are to evaluate the test-retest reliability, internal consistency, factor structure, and external validity of this instrument in methadone maintenance, intensive outpatient, standard outpatient, residential, correctional, and welfare samples. The STEP is intended to fill a gap between instruments that measure functional impairment from substance abuse (e.g., the ASI), and those that measure clients' attitudes about the need for change (e.g., the URICA or SOCRATES). By connecting specific conditions in a
Studies 33
clients life to his or her desire for change, the STEP will provide important information to clinicians and researchers about the elements and determinants of motivation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL PSYCHOBIOLOGY OF AFFECT IN INFANTS Principal Investigator & Institution: Blass, Elliott M. Professor; Psychology; University of Massachusetts Amherst 408 Goodell Building Amherst, MA 01003 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-JAN-2004 Summary: (Adapted from applicant's abstract): This research focuses on short and longterm changes that human mothers cause in their infants during nursing. In newborns it assesses how mothers protect against pain by combining orosensory (milk or sucrose) and tactile (pacifier sucking) aspects of the mother to determine the interactions between afferent systems during and following fluid infusion. Metabolic consequences of tasting sucrose of mile or sucking a pacifier will be evaluated via direct calorimetry. We have already demonstrated substantial reduction heat loss in infants tasting sucrose. Energy savings is common to the behavioral and physiological changes induced by sucrose and may serve as a basis for their selection. Opioid mechanisms underlying orosensoryinduced changes will be assessed in infants with a prenatal methadone history. In principal, these infants, whose endogenous opioids have been reduced, should not respond to sweet taste but should be calmed by a pacifier. The role of nonnutritive sucking in conserving energy in those infants will be determined. We will also determine the stable and changing proximal maternal stimuli that calm distressed 6 to 12-week olds and serve as a basis for maternal preference. We have shown that orosenory stimulation claims at 2-weeks; it must be combined with visual engagement to calm 4-9 week olds. This combination does not calm at 12 weeks. The need for eye engagement to calm 4-9-week-old infants leads us to investigate whether these infants use internal facial features to recognize familiar adults or to continue to rely on external features as do newborns. This is an important issue from the perspective of what defines familiarity and safety, the experiences necessary to cause these changes and the underlying neurology. This research will reveal behavioral, metabolic, and physiological consequences of nursing-suckling interactions during the first three postnatal months. It will impact on patient treatment from the perspective of pain management and recovery from remarkable prenatal histories. It makes significant empirical contributions to what infants can and do learn during nursing and its biological significance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIRECTLY OBSERVED ANTI RETROVIRAL THERAPY AMONG ACTIVE D Principal Investigator & Institution: Altice, Frederick L. Associate Professor of Medicine; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (Applicant's Abstract) The use of highly active antiretroviral therapy (HAART) has resulted in marked reductions in AIDS incidence, mortality and hospitalization. Unfortunately, these successes have not been uniform among all groups of people living with HIV, particularly among HIV infected injecting drug users (IDUs). The stunning benefits of HAART have been blunted and limited by difficulties in access and adherence to therapy. Despite the impressive successes of directly observed therapy (DOT) for tuberculosis control, only a few pilot studies of this intervention have been
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implemented for the treatment of HIV disease. Most of these studies of DOT using HAART have been accomplished in the controlled setting of either methadone maintenance or prisons, yet as few as 15-20 percent of IDUs are likely to be in these settings. For those who are in these settings, relapse to active drug use is common. Thus, in order to accomplish increased access to and utilization of HAART by HIV infected IDUs, innovative programs that effectively reach out-of-drug treatment IDUs are desperately needed. One such way to effectively interact with these IDUs is through needle exchange programs (NEPs). In this study, we propose to conduct a randomized, controlled trial comparing modified DOT dispensed HAART through NEP-based health services to standard of care. Recruited subjects of out-of-drug treatment HIV+ IDUs will be randomized based on census-block code and experience with antiretroviral therapy. Modified DOT will be administered to the intervention group; for twice daily regimens, they will receive one dose per day as DOT and will receive a programmed reminder to take their next dose on their own. Primary endpoints include standardized measures of adherence, reduction in HIV-1 RNA levels and time to development of a primary HIV-1 resistance mutation. Secondary measures of interest include quality of life measures, health care utilization and entry into drug treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIRECTLY OBSERVED ANTIRETROVIRAL THERAPY IN DRUG ABUSERS Principal Investigator & Institution: Lucas, Gregory M. Medicine; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 10-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The early years of the combination antiretroviral therapy (ART) era have brought about dramatic reductions in the morbidity and mortality associated with HIV infection in industrialized countries. Yet, the critical importance of adherence in optimizing treatment outcomes quickly became evident. My prior work has shown that injection drug users (IDUs) underutilize ART, and are at high risk for inadequate adherence and poorer treatment outcomes when therapy is used. Tuberculosis treatment with directly observed therapy (DOT) has proven remarkably effective in addressing issues currently being confronted in HIV management promoting adherence, achieving clinical success, and avoiding drug resistance. Methadone maintenance is an effective treatment for opiate addiction and provides a feasible setting in which directly administered antiretroviral therapy (DAART) may be provided to HIV-infected patients. I propose to conduct a prospective clinical study to determine the effectiveness of DAART provided in a methadone maintenance clinic. Clinical outcomes will be compared in DAART participants and matched participants in the Johns Hopkins HIV Cohort Study. My hypothesis is that DAART will be effective in a methadone treatment center and will be associated with improved HIV treatment outcomes compared to standard care. The specific aims of this project are to 1) assess 1year retention in DAART and associated factors, 2) assess the temporal trend of adherence in DAART and its association with viral suppression, 3) compare virologic and immunologic responses to therapy in DAART participants and matched patients receiving standard care, and 4) compare the incidence of opportunistic diseases and death in DAART participants and matched patients receiving standard care. This proposal builds directly on my prior work and lays the foundation for a randomized, multi-site trial of the DAART strategy. My career development plan is based on the Graduate Training Program in Clinical Investigation, which includes comprehensive coursework at the Johns Hopkins School of Public Health, structured mentoring, and
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guidance from a thesis committee. My career plan and research proposal are consistent with my long-term goals of becoming an effective independent investigator, and optimizing treatment outcomes in HIV-infected IDUs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISCRIMINATIVE STIMULUS EFFECTS OF OPIOID WITHDRAWAL Principal Investigator & Institution: France, Charles P. Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-MAY-2003 Summary: Despite the availability of several, effective pharmacotherapies, opioid abuse continues to pose a major public health problem worldwide. Currently available pharmacotherapies are effective in only some patients and the need continues for new and better treatments for opioid abuse. Prior research under this grant developed discrimination procedures for studying opioid dependence and withdrawal. Studies in this application will use those, and other, procedures to examine the development of dependence to novel opioids and to test hypotheses regarding drug interactions and the possible attenuation of dependence and withdrawal. Specific Aim I will determine whether opioid or non-opioid tolerance or dependence develops during treatment with the novel fentanyl derivative mirfentanil. Specific Aim II will examine the role of P450 enzymes in the morphine-like effects of codeine and oxycodone and determine whether other drugs (N-methyl-D-aspartate antagonists [NMDA] and nitric oxide synthase [NOS] inhibitors) modify opioid tolerance and dependence. These studies will compare methadone and its stereo isomers because these opioids also have effects at NMDA receptors. Upon completion of a study on LAAM dependence and withdrawal, studies under Specific Aim III will test the hypothesis that variations among mu opioids in their effects on receptor internalization and G-protein coupling will be expressed as differences in tolerance and dependence. Naltrexone will be established as a discriminative stimulus in untreated monkeys (Specific Aim IV) to begin a characterization of behavioral effects that might be important to the therapeutic utility of these drugs (e.g., alcohol abuse). Specific Aim V will use pigeons to study efficacy and selectivity differences among opioids and also to determine whether hypothesized interactions between different opioid receptors has functional consequences for drug dependence and withdrawal. The procedures developed under this grant provide a unique set of conditions for evaluating the effects of other drugs on behaviors related to and predictive of the subjective effects of withdrawal in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISULFIRAM FOR COCAINE ABUSE IN METHADONE- PATIENTS Principal Investigator & Institution: Oliveto Beaudoin, Alison; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-MAR-2006 Summary: (Applicant's Abstract) Because cocaine use remains epidemic among most opioid maintenance programs and pharmacological therapeutic strategies specifically aimed at cocaine's dopaminergic actions have shown little efficacy in unselected populations, this proposal will examine a novel pharmacological strategy for treating cocaine abuse in opioid-maintained cocaine abusers; i.e., treatment with disulfiram. Specifically, the aim of this proposal is to examine the effects of disulfiram (0, 62.5, 125, or 250mg /day) on treatment outcome in methadone-maintained cocaine abusers. This 14-wk, double blind, randomized clinical trial will provide treatment for 160 opioid- and
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cocaine-dependent individuals (18-65 years). Participants will be placed on methadone maintenance during weeks 1-2, at which time level of cocaine use is assessed. Then participants will continue on methadone maintenance and be randomly assigned to receive one of the following doses of disulfiram: 0, 62.5, 125, or 250 mg/day. During stabilization on methadone (wks 1-2), participants typically are administered increasing doses of methadone on a daily basis until maintenance doses are attained. Then during the treatment phase (weeks 5-14), participants continue to receive their daily maintenance doses of methadone.. In addition, they receive disulfiram/placebo on a daily basis. At the end the study, participants will undergo detoxification from methadone over a 4-week period. In order to enhance outcome, all participants receive weekly 1-hour psychotherapy (Cognitive Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. The primary outcomes will be retention and reduction in opioid and cocaine use, as assessed by self-report and confirmed by thrice-weekly urinalyses. Secondary outcomes will include reductions in other illicit drug and alcohol use, as well as improvements in psychosocial functioning. The prognostic relevance of genotype at the dopamine beta-hydroxylase locus, dopamine beta-hydroxylase enzyme activity, and severity of cocaine dependence will also be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG ABUSE AND RESISTANCE TO ANTIRETROVIRAL THERAPY Principal Investigator & Institution: Markham, Richard B. Professor; Molecular Microbiol and Immun; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 24-AUG-2000; Project End 31-JUL-2005 Summary: Resistance to antiretroviral therapy always results from selection for resistant viral variants. The resistance genotype can either be pre-existing, frequently as a minority clone, before the initiation of therapy or it can emerge due to ongoing viral replication that occurs despite therapy. In either case the development of a drugresistance mutation arising during the HIV-1 life cycle is likely a random event, dependent on the rate at which new mutations arise generally in the HIV-1 population existing within an infected individual. The appearance of new mutations, in turn, will reflect intrinsic replicative properties of a given viral variant, as well as host factors, such as T cell activation state or co-receptor expression, that facilitate replication of specific viral variants. We have recently determined that one host factor not frequently considered as a source of increased viral replication, frequency of injection drug use, is positively and highly significantly associated with diversity in the env gene of HIV-1 infected injection drug users. This increase is not due to infection with a second virus and may be attributable to opiate-induced enhancement of viral replication, which has been observed in tissue culture systems. It is likely that this increased diversity will extend to viral genes other than env, including pol. Based on these findings we hypothesize that multi-drug resistant mutants will emerge more readily among injection drug users and those on methadone maintenance programs than in drug-free control subjects. To address this hypothesis we will evaluate specimens collected from over 40 women by the Women's Interagency HIV Study to answer the following questions: 1) Is the higher rate of viral genetic diversity observed in the env gene in frequent drug injectors also observed in the pol gene? 2) Is the higher rate of genetic diversity observed in frequent injection drug users also observed in individuals taking methadone? 3) Does a history of injection drug use or methadone use result in a higher incidence of resistance to HAART? The findings from this study should have important implications
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for the clinical approach to control of opiate addiction and antiretroviral therapy in the HIV-1- infected, drug-infected population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LINKAGES
DRUG
ABUSE
TREATMENT
EMERGENCY
DEPARTMENT
Principal Investigator & Institution: Sorensen, James L. Professor of Psychiatry; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002 Summary: (Applicant?s Abstract) Drug abusers with complex problems have frequent contact with medical emergency departments. Emergency departments can assist patients in accessing drug abuse treatment and linking with less acute care. This randomized trial will test the effects of two linkage strategies: (1) transitional case management; and (2) vouchers for free methadone treatment --- with opioid-dependent injection drug users recruited from the emergency department of a public general hospital. The primary aims are to test the effects of the interventions on: (1) enrolling participants in drug abuse treatment; (2) enrolling participants in medical and social services; (3) improving opioid use outcomes; and (4) changing participants? pattern of utilization of acute health services. Participants will be opioid-dependent injection drug users recruited at a hospital-based emergency department, randomly assigned in a twoby-two factorial design to receive: (1) transitional case management, (2) vouchers for free methadone treatment, (3) case management and vouchers, or (4) usual care (brief contact and referral). Case management will have a cognitive behavioral focus. Assessments will occur before randomization and follow-up assessments at 6, 12 and 18 months. Primary hypotheses will test the effects of: (1) vouchers on enrollment in drug abuse treatment; (2) case management on enrollment in other services; (3) the combination of vouchers and case management in reducing opioid use; and (4) case management on the cost of health care used by the participants. To identify predictors of participation and retention, the study will gather information about the treatment process and prepare treatment manuals that can be used in other settings. The treatment research effort will assess innovative models linking health care with drug abuse treatment. It contributes to cross-component TRC studies, including self-referral versus voucher-referral with Dr. Batki, nicotine dependence with Dr. Hall, and measurement of process variables with Dr. Havassy. It also contributes to collaborative studies described in the TRC core, including drug abuse treatment and statistical analyses, psychiatric and substance abuse comorbidity, and assessing the environments of opioid abusers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG ABUSE TREATMENT SYSTEM SURVEY Principal Investigator & Institution: D'aunno, Thomas A. Associate Professor; None; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 01-MAR-1983; Project End 24-MAY-2003 Summary: (Applicant's Abstract) The proposed study has two overall goals. First, it will monitor changes in treatment practices in the nation's outpatient drug abuse treatment units to determine the extent to which they are meeting known or desired standards of care. Information will be gathered on several important treatment practices, including: treatment duration and intensity; clients' use of primary health care, mental health care, and social services; HIV prevention practices; availability of special services for women and ethnic minorities; and methadone dose levels. Second, this study will examine how
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key organizational and community factors (e.g., unit ownership) account for change and variation in treatment practices. For example, how are various managed care arrangements affecting treatment duration and intensity, and clients access to social and health services? To achieve these goals, the National Drug Abuse Treatment System Survey (NDATSS) will be continued in 1999. The 1999 data will give us a current picture of treatment practices across the nation (n=600 treatment units). Further, with the addition of the 1999 survey, we will have data from a representative national sample of outpatient nonmethadone and methadone units for 1988, 1990, 1995, and 1999. The majority of treatment units to be included in the 1999 sample (n=387) have already participated in NDATSS in 1988, 1990, and 1995. Thus, we will be in a strong position to monitor changes in treatment practices over a decade (1988-1999), and to make causal inferences about these changes that can inform both policy and practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG ABUSE TREATMENT SYSTEM SURVEY Principal Investigator & Institution: Alexander, Jeffrey A. Richard Carl Jelnick Professor; Hlth Svcs Management & Policy; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 25-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): The proposed study has two major goals. First, we will determine the extent to which the nation's outpatient drug abuse treatment units are using treatment practices and providing services that meet empirically-established standards of care in several key areas. These areas include: treatment duration and intensity; clients' use of primary health care, mental health care, and social services; HIV and Hepatitis prevention efforts; availability of special services for women and ethnic minorities; methadone dose levels; and access to treatment. We will examine both variation and changes in these treatment practices and services. Second, we will identify organizational factors (e.g., units' managed care arrangements, ownership, staffing) associated with variation and change in treatment units' practices. These factors include unit: ownership; accreditation; funding sources and mechanisms--especially managed care; location (both geographic location and location in a parent organization such as a hospital); community demographic characteristics and health care resources; referral sources; treatment goals/philosophy; staff and client characteristics. To achieve these goals, we will continue the National Drug Abuse Treatment System Survey (NDATSS) in 2003. The 2003 data will give us a current picture of key practices and services in treatment units across the nation (n=600 treatment units). Further, with the addition of the 2003 survey, we will have data from a representative sample of outpatient nonmethadone and methadone units for 1988, 1990, 1995, 1999/2000 and 2003. More than half of the treatment units to be included in the 2003 sample (n=324) have already participated in NDATSS in 1988, 1990, 1995, and 2000; and, 489 units participated in our study in both 1995 and 2000. Thus, we will be in a strong position to monitor changes in practices over 15 years (1988-2003), and to make causal inferences about determinants of these changes to inform both policy and practice. In short, NDATSS is well-positioned to become the critical source of information for monitoring and analyzing the on-going evolution of the nation's outpatient drug abuse treatment system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUG DISCRIMINATION AND TOLERANCE TO COMMONLY ABUSED DRUGS Principal Investigator & Institution: Stahl, Jeanne M.; Morris Brown College 643 Martin Luther King Dr Nw Atlanta, GA 30314 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-DEC-2005 Summary: (Applicant?s Abstract): There are 10 aims for this project involving two different lines of research. We propose to do the following: (1) to investigate the effects of three levels of weight reduction (0 percent, 10 percent, and 20 percent) on rate of acquisition and asymptotic performance on a two-lever drug discrimination task with gamma-hydroxybutyrate (GHB) vs. saline; (2) To test the discriminative stimulus properties of GHB, gamma-butyrolactone (GBL), flunitrazepam (Rohypnol), and ethanol; (3) To investigate discriminative stimulus properties of GHB and GBL when given as mixtures with ethanol; (4) To partially replicate and extend preliminary results on the effect of reinforcer type on the development of tolerance to reinforcer magnitude; (5) To determine the extent to which reinforcement context affects the development and degree of tolerance to amphetamine and morphine; (6) To determine the extent to which reinforcer magnitude affects the development and degree of tolerance to amphetamine and morphine; (7) To elucidate the role of behavioral variables in modulating the behavioral effects of drugs and to highlight their potential for the treatment of drug abuse; (8) To write a comprehensive review of the literature on the status of the concept of state dependent learning (SDL) vs. drug discrimination, to seek feedback from the few existing SDL researchers, and publish in a review journal; (9) To design experiments to partially replicate and extend our research with the Maier 3-table reasoning problem to determine whether rats that demonstrate a performance deficit when experiences are given under morphine and saline demonstrate similar deficits when tested with combinations of methadone and saline or buprenorphine and & saline; and (10) To expose high school, undergraduate, and graduate minority students to a variety of research methods used in behavioral pharmacology in order to prepare them for admission to and retention in excellent graduate research programs and, potentially, drug abuse research careers. Students will be involved in every aspect of this research including research ethics, animal care and handling, animal behavioral testing, data analysis, library research, literature review, and preparation of papers for presentation and publication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUG RELATED CNS DAMAGE-SYNERGY WITH EFFECTS OF HIV Principal Investigator & Institution: Bell, Jeanne E.; University of Edinburgh Edinburgh Eh8 9Yl, Scotland Edinburgh, Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: (from applicant's abstract): Drug misuse by injecting is a global problem, which is increasing in incidence in many countries, and which is associated with increased morbidity and mortality particularly in young people. Injecting drug use is also a major risk activity for the spread for HIV infection. This project will study drug and HIV related neuropathology and Apolipoprotein E polymorphisms in a clinically well-characterized cohort of drug users in Edinburgh, Scotland, who have a high prevalence of chaotic and injecting drug use, and of HIV infection. Their lifetime drug history, and premorbid and comorbid neuropsychological and general health status is well documented. Despite early identification of the HIV epidemic in this group, and a program of methadone substitution, the mortality rate has been high, both from drug-
40 Methadone
related causes and from associated HIV and hepatitis C infections. The cohort has been characterized by a very high prevalence of HIV encephalitis [59 percent] when they progressed to AIDS. This study will include patients with pure HIV encephalitis who did, or did not, use drugs, drug users who were HIV negative and controls who were neither HIV infected nor used drugs. Histological and immunocytochemical methods will be applied to detect neurodegenerative changes particularly in the basal ganglia, central white matter and brain stem nuclei, and to quantify acute and chronic damage to the blood brain barrier. It is expected that the targets of drug and HIV related neuropathology will overlap and that the damage will be cumulative in patients who are both drug users and have HIV encephalitis. In order to explore further the question of why individuals vary in their susceptibility to the damaging effects of drugs, it is proposed to investigate Apolipoprotein E polymorphisms in the cohort since this gene exerts a major influence on other neurodegenerative and cerebrovascular diseases and has been linked to HIV related cognitive decline. Further cases will be recruiter] in order to study this possible synergy between and drug use in the more recent context of combination drug therapy. Morbidity problems associated with drug misuse are a significant drain on the health budget of many nations, quite apart from the more general impact on society. Identification of particularly hazardous patterns of illicit drug(s) use, and of possible genetic susceptibility, could lead to more focused prevention and intervention strategies in at risk cohorts and individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUGS OF ABUSE AND POTENTIAL THERAPEUTIC AGENTS-EFFECT ON OPIATE RECEPTORS Principal Investigator & Institution: Unterwald, Ellen;; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUGS OF ABUSE: CHRONIC INTERACTIONS AND BEHAVIOR Principal Investigator & Institution: Mcmillan, Donald; Chairman & Wilbur D. Mill's Professor; Pharmacology and Toxicology; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, AR 72205 Timing: Fiscal Year 2002; Project Start 01-JUN-1978; Project End 30-JUN-2006 Summary: (provided by applicant): Drug discrimination has become one of the most powerful methods available for studying the internal stimuli produced by drugs of abuse. Most drug-discrimination research has focused on the discriminative stimulus effects of single drugs; however, there is extensive evidence that many drug users combine two or more abused drugs. The combined administration of two or more drugs has been investigated on only a small minority of drug-discrimination studies because the behavioral technology available has limited the number of choices that the subject can make in reporting the stimulus effects of drugs to two or three choices. During the previous project period, we have developed an innovative new four-choice procedure for the study of drug discrimination that allows animals to discriminate among two different drugs, a mixture of these two drugs, and the absence of the mixture and either of the drugs in the mixture during a single test session. This procedure should enhance both the sensitivity and the selectivity of the drug-discrimination process for comparing the effects of drug mixtures to the effects of each of the drugs in the mixture. The four-
Studies 41
choice procedure will be used to study interactions between morphine and pentobarbital, between dizocilpine and pentobarbital, between methadone and aiprazolam, and between other drug mixtures. The data should provide important evidence about how these drug mixtures interact to produce their effects on the central nervous system. The four-choice procedure should also be very useful for studying the effects of drugs, such as ethanol, that interact with several subclasses of receptors. By training subjects to discriminate among ethanol, that dizocilpine, and pentobarbital, and then studying the discriminative stimulus effects of mixtures of dizocilpine and pentobarbital, it may be possible to delineate the relative contributions of GABA and NMDA receptor interactions to the discriminative stimulus properties of ethanol. Similar types of experiments will be done to determine the role of mu, kappa and delta opioid receptors to the discriminative stimulus effects of opioid drugs that produce complex actions mediated by interactions at several receptor sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EDUCATION ON OPIATE ADDICTION AND TREATMENT Principal Investigator & Institution: Tanner, T Bradley. President; Clinical Tools, Inc. 431 W Franklin St, #30 Chapel Hill, NC 27516 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 31-AUG-2003 Summary: (provided by applicant) Our goal is to educate primary care physicians and physicians-in-training on the recognition and treatment of opiate addiction by developing an Internet-based continuing education (CE) curriculum consisting of seven courses. One course was created and evaluated in Phase I of this project. That course improved knowledge and self-efficacy in a group of 23 residents and resulted in high satisfaction. The course was qualified for 1.5 hours of American Academy of Family Physicians (AAFP) CE credit. Phase II will create six additional courses based on research findings, guidelines, consultant input, literature review, and expert panel recommendations. A standard rapid-prototyping formative analysis technique will utilize input from physicians and expert consultants to produce successively improved versions of each course as input is received. The final courses will be presented to the Center for Continuing Education at the University of Pittsburgh, the University of North Carolina, Chapel Hill, and the AAFP for CE credit. In Phase II we will evaluate the suite of courses for their effect on: knowledge, clinical skills, self-efficacy and reported behavior using a two group, pre-post testing design. We will also assess overall user satisfaction with the online learning experience in terms of course elements, comparison to other learning experiences, and perceived impact. If the courses are successful, this project will produce a new means to educate physicians in opiate addiction diagnosis and treatment techniques. The methodology used in this research will serve as a template to guide other Investigators interested in developing substance abuse continuing education materials. PROPOSED COMMERCIAL APPLICATION: Not Available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF BUSPIRONE IN WITHDRAWAL FROM OPIATES Principal Investigator & Institution: Buydens-Branchey, Laure B. Acting Associate Chief of Staff; Narrows Institute for Biomedical Res Inc Biomedical Research, Inc. New York, NY 11209 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-AUG-2003
42 Methadone
Summary: (provided by applicant): The goal of this project is to evaluate the efficacy of a non-opiate medication, buspirone, for the alleviation of withdrawal symptoms in heroin addicts who wish to discontinue heroin use. There is preclinical evidence that buspirone attenuates withdrawal symptomatology resulting from the interruption of morphine administration. In a double-blind, placebo controlled pilot study, we observed that buspirone given as a daily dose of 30 mg was more effective than placebo in alleviating objective and subjective withdrawal symptoms in heroin addicts in the course of detoxification. This project proposes to randomize 75 heroin addicts seeking inpatient detoxification to 5 groups over a 2-year period. The trial will start with a 5-day period of stabilization on methadone.. On the last 2 stabilization days, the methadone dose will be 30 mg. Group I will then be given a placebo, group II methadone in tapering doses, group III clonidine and group IV and V buspirone (30 mg and 45 mg daily). On day 14, drugs and placebo will be discontinued and patients observed for 3 days. The trial will be double blind. Withdrawal signs, psychological changes, sleep patterns and heroin craving will be monitored throughout the trial. The agents most frequently used for heroin detoxification, clonidine and methadone have advantages as well as disadvantages. Clonidine does not suppress all withdrawal symptoms and a methadone taper can be used only in licensed clinics and can be lengthy. If buspirone proved effective in alleviating heroin withdrawal symptoms as could be anticipated in light of the pilot data presented in this application, it could be used to shorten the duration of the inpatient or outpatient detoxification of heroin addicts. Buspirone has additional advantages. It is not sedating, has no withdrawal symptoms, has no abuse potential, does not potentiate central nervous system depressants and does not induce psychomotor impairment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF DRUGS OF ABUSE & POTENTIAL THERAPEUTIC AGENTS --EXPRESSION OF HPA AXIS Principal Investigator & Institution: Zhou, Yan;; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF OPIOIDS ON SLEEP AND FATIGUE Principal Investigator & Institution: Dimsdale, Joel E. Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The goal of this R21 application is to refine an experimental design to examine the impact of commonly used pain medications on sleep and next-day fatigue. However, before such studies can be conducted in patients with acute or chronic pain associated with cancer or other severe chronic illness, crucial information is needed to optimize the study design. This proposal seeks to answer certain experimental methodological design questions that can be safely, quickly, and inexpensively addressed in healthy volunteers. This R21 application will generate data guiding the research design and power estimates for subsequent RO1 applications intended to address the impact of pain medication on sleep and fatigue in patients with acute or chronic pain. There are 5 specific aims: 1. Characterize the effect of a typical nighttime dose of MS-Contin and methadone on cytokines, polysomnographic sleep
Studies 43
and on rest/activity patterns in healthy volunteers: 2. Characterize daytime fatigue the day after drug administration with self-reported measure of fatigue and mood 3. Characterize neuropsychological performance on the day after drug administration. 4. Estimate the covariance structure of sleep measures to assess the comparative advantages of a crossover or parallel groups design. 5. Evaluate the necessity of repeated first nights and whether this is the optimum design for follow-up studies. Over a two-year period, 50 healthy volunteer subjects will be examined with polysomnography, actigraphy, and neuropsychological tests. Data will be collected on self-reported mood and fatigue, as well as proinflammatory cytokine levels (IL-6, IL1beta, and TNF-alpha. The study design involves a double-blind, placebo-controlled crossover. Each individual will be admitted to the UCSD GCRC on 3 pairs of nights. Each admission will feature an acclimation night in the sleep laboratory followed by a night providing placebo, MS-Contin (15 rag) or methadone (5 mg). On the morning after each dosing subjects will complete fatigue and mood ratings and will perform a brief neuropsychological test battery. They will also undergo actigraphy monitoring for 3 continuous days to examine whether there are subtle lingering effects of the drugs. Blood levels ofproinflammatory cytokines will be obtained at various points before and after drug dosing and the next morning to test the hypothesis that opioid-induced changes in these cytokines are associated with sleep disruption and increased fatigue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFICACY AND COST OF HAART DOT IN METHADONE CLINICS Principal Investigator & Institution: Arnsten, Julia H. Associate Professor; Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Drug users account for a substantial proportion of AIDS cases; yet have received disproportionately less benefit from highly active antiretroviral therapy (HAART) than non-drug users. Recent reports have shown that HAART is under-utilized among drug users, and that persons with a history of injection drug use may be less likely to achieve the level of adherence necessary to maintain viral suppression than non-drug users. In order to improve both access to HAART and adherence among HIV-infected drug users, new models of integrated HIV-related and substance abuse treatment are rapidly evolving. One innovative model by which to deliver such treatment, provision of HIV primary care on-site in a methadone maintenance program has been shown to improve health outcomes in several studies. Directly observed therapy (DOT), effective in treating tuberculosis in methadone programs and other settings, is a logical extension of this model that has the potential to markedly enhance adherence with HAART. However, only preliminary findings from studies of the effectiveness of DOT for HIV have been reported, and these data are not consistent. While 80-100% of HIV DOT patients have achieved undetectable viral loads in some uncontrolled studies, other pilot DOT studies have found that the proportion achieving this outcome is 60-65%. In addition, DOT for HIV may paradoxically increase the risk of drug resistance by fostering moderate improvements in adherence. Rigorous data are necessary to judge the contribution of DOT to the success of HIV treatment among drug users, particularly among drug users in methadone maintenance treatment. By performing a randomized trial of HAART DOT in methadone maintenance clinics at which HIV primary care is provided, we will be able to evaluate the efficacy and cost-effectiveness of DOT. The specific aims of this proposal are: (1) To determine in a randomized trial whether directly observed HAART, provided on-site at a methadone clinic during a 24-week study period, is more effective than self-
44 Methadone
administered HAART for reducing HIV viral load and increasing CD4 count, (2) To assess the durability of DOT as an adherence-enhancing intervention by comparing long-term adherence in the DOT and self-administered groups, using self-report and electronic monitors to measure adherence 3, 6, and 12 months after DOT is discontinued, and (3) To perform cost, cost-offset, and cost-effectiveness analyses of directly observed HAART. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFICACY OF LAAM MAINTENANCE FOR OPIOID DEPENDENT PREGNANT WOMEN Principal Investigator & Institution: Schnoll, Sidney;; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001 Summary: To evaluate the efficacy of Levo-alpha-acetylmethadol(LAAM) as a maintenance drug in pregnant opioid-dependent women. Both the transfer from methadone to LAAM and LAAM maintenance will be characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ELIMINATION OF METHADONE BENEFIT FROM OREGON HEALTH Principal Investigator & Institution: Fuller, Bret E. Public Health and Prev Med; Oregon Health & Science University Portland, OR 972393098 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Significant changes in the Oregon Health Plan (OHP) have created a unique opportunity to investigate impacts on patients enrolled in methadone maintenance services when the Oregon State Legislature eliminated payment for methadone maintenance and outpatient chemical dependency services for those under the Medicaid expansion, Oregon Health Plan-Standard. Approximately 5,000 clients in Oregon were enrolled in methadone services and 3,000 were receiving OHP Standard prior to these cuts. Thus, beginning March 1, 2003, 3,000 patients were required to self-pay in order to continue receiving methadone services. This study is currently following 151 methadone clients recruited in February and March 2003 and randomly selected to participate in this project. The sample selection was a randomized quasi-experimental study of three groups of clients, (a) those who lost their benefits and were removed from methadone involuntarily, (b) those who attempted to pay out of pocket for methadone, (both received benefits under the OHP Standard) and (c) those who retained their benefits through Medicaid (OHP-Plus). The first wave of data collection began in February 2003; with a second wave in the first weeks of April 2003; and a third data collection point is scheduled for June 2003. Interviews with the Addiction Severity Index, Treatment Services Review and Health Risk Behavior Survey and a chart review of clinical data constitute the first three waves of data collection. This application seeks funding for a one-year follow up interview (Wave 4) as a continuation of earlier work funded by the Robert Wood Johnson Foundation (4/15/03-7/15/03 for $20,000) and the Oregon Practice Improvement Collaborative (2/1/03-3/31/03 for $10,000). Data from clients' clinical records one year following the beginning of the study and abstraction of data from four Oregon administrative databases that monitor legal, employment, addiction services and Medicaid reimbursements will round out the data collection for this project. All four completed interviews will provide time series data on the Addiction Severity Index scales (drug use, alcohol use, legal problems,
Studies 45
medical problems, family problems, employment problems, and psychiatric problems), participation in mental health, addiction treatment and health care services (Treatment Services Review), and HIV risk behaviors (Risk Behavior Survey). The analysis for these data will present characteristics of methadone clients with respect to differences between the three groups. Means, standard deviations and ranges of the ASI composite scores will be presented examining the levels of addiction behaviors that characterize the sample. Demographic variables including age, gender, length of addiction, dosing levels will also be presented at all four waves. Also, a description of how many OHPStandard patients were able to successfully self-pay for their methadone treatment on their own will be presented. The main part of the analysis will consist of structural equation models that will be used to isolate slopes and intercepts for addiction behaviors over time, examining any differences between the three client groups and the mediators and moderators of these growth curves. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENHANCING HEALTH CARE OF DRUG USERS WITH HIV Principal Investigator & Institution: Mccance-Katz, Elinore F. Associate Professor; Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001; Project Start 05-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant) This application is an extensive revision of the K02 application which had been entitled "HIV disease and Drug Abuse: Medications Development." This resubmission expands upon the career development plan to describe related grants and collaborations that link drug abuse, infectious disease with a principal emphasis on HIV disease, and epidemiology using the human laboratory as a tool to explore research questions that span these areas. As a result the resubmission has been retitled "The Human Laboratory: Enhancing Health Care of Drug Users with HIV." This K02 is built around RO1 grant DA13004 "Opiolds and HIV Medications: Interactions in Drug Abusers" (PI: E. McCance-Katz). The aim of this project is to enhance the care of patients with HIV disease and opiold dependence by using the human laboratory setting to identify significant drug interactions between opioids and antiretroviral medications. These findings will assist clinicians by identifying drug combinations likely to have substantial interactions that can lead to non-adherence, by assisting with the process of matching patients to treatments, and may improve adherence with decreased medical complications of AIDS as well as reduced transmission of the virus. Related collaborative efforts are a key component of the career development plan and include a study of directly observed HAART therapy in methadone maintained individuals (PI: E. McCance-Katz, M. Gourevitch, J. Arnsten), determination of methadone and antiretroviral drug concentrations and correlation with HIV therapeutics adherence (PI: J. Amsten, E. Schoenbaum), determination of HAART effectiveness in late stage HIV in drug users (PI: D. Vlahov, B. Greenberg), and methadone maintenance in primary care settings (PI: S. Magura). Additional prongs of the career development plan include didactics specifically aimed at enhancing knowledge and ability to contribute to these projects. Molecular pharmacology, epidemiology, and research ethics courses are proposed as is substantial time meeting with other experts and mentors including T. Kosten, R. Schottenfeld, P. Jatlow, G. Friedland, P. Rainey, E. Morse, and M. Fischman. This revised application also includes a career development path in teaching and mentoring trainees with an interest in drug abuse research. The Albert Einstein College of Medicine and the surrounding, New York City and New Haven areas provide an ideal environment for continuing progression as an independent clinical researcher in drug abuse and HIV disease.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF HIV1 AMONG OPIATE USERS IN N THAILAND Principal Investigator & Institution: Celentano, David D. Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2003 Summary: (Applicant's Abstract) This study is designed to elucidate the epidemiologic risk factors for prevalent and incident HIV-1 infections among opiate users in northern Thailand, and to determine whether methadone maintenance is associated with reduced relapse to narcotics use as compared to methadone-assisted detoxification on an outpatient basis. These studies will be accomplished by interviewing and screening all first admissions to the Northern Drug Dependence Treatment Center in Mae Rim (Chiang Mai Province), Thailand, a facility operated by the Department of Medical Services, Ministry of Public Health. Approximately 1,750 first admissions are seen per year, and will comprise the prevalence study. Currently, about 25% of injectors are HIV infected on admission and 8% of opium smokers have antibody to HIV. A prospective cohort study will be conducted among persons seeking readmission to the NDDTC over a two year period, as well as opiate users who relapse following treatment and are seen in an outpatient opiate detoxification program or who reside in village settings within 100 km of the NDDTC. A total of 800 relapsed opiate users will be followed for two years to study endpoints, and we will determine the incidence of HIV infection. We will also conduct a randomized controlled trial of outpatient methadone maintenance vs. methadone assisted detoxification among 480 opiate users seeking treatment for drug abuse, with the primary study endpoint being relapse to opiate use; secondary outcomes include incident sexually transmitted diseases and drug use-related HIV risk behaviors; HIV incidence will be measured as well. These data on the epidemiology of HIV infection among drug users have relevance for other southeast Asian countries experiencing a dramatic HIV epidemic, in which opiate use plays an important role directly through sharing of injection equipment, and as a bridge to the general heterosexual population through unprotected sexual behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EVALUATING SUPERVISED HAART IN LATE STAGE HIV IN IDUS Principal Investigator & Institution: Vlahov, David H. Director; New York Academy of Medicine 1216 5Th Ave New York, NY 10029 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-JUL-2003 Summary: We propose a prospective study to determine the impact of chronic viral hepatitis and methadone on rates of treatment failure of highly active antiretroviral therapy (HAART) among patients with late-stage HIV infection. Prior exposure to mono or combination antiretroviral therapy and lack of adherence to complex HAART regimens are believed lead to HIV-1 resistance and virologic failure of HAART. However, additional co-factors of treatment failure need evaluation. Our preliminary data suggest that chronic viral hepatitis (which may lead to liver intolerance or upregulate HIV-1) may be important. The role of methadone (which may interact with HAART regimens to decrease effectiveness and cause side effects) also merits study. The study population will be 350 patients recruited from the residential health care facilities (RHCFs) in New York City with over 1200 beds devoted to long-term care for patients with late-stage HIV infection; 85 percent are minority men and women; 55 percent have
Studies 47
prior experience with a protease inhibitor and 80 percent receive supervised HAART. HAART is administered and monitored by the nursing staff which should limit the impact of noncompliance. Fifty four percent have chronic viral hepatitis and 66 percent have experience with injection drugs (40 percent of whom receive methadone maintenance). Patients will be followed prospectively at 4 and 8 weeks and quarterly thereafter for up to nine months. At the time of study entry, antiretroviral therapeutic decisions will be guided by a combination of careful treatment history, genotypic resistance testing with expert clinical interpretation and treatment recommendations which should limit the impact of HIV-1 resistance for previous treatments. Data collection at research visits will include medical record review (for clinical and routinely collected laboratory parameters, nurse medication administration records), patient interviews (for self-report medication acceptance and medication adherence) and venipuncture (for genotypic resistance testing, additional HIV virologic and immunologic assays, specimen repository for future studies including phenotypic resistance assays and protease inhibitor trough levels). Analysis of the primary outcome, virologic treatment failure (as defined by the AIDS Clinical Trials Group), will be done using survival and longitudinal data analytic techniques. By conducting this study in this unique RHCF setting where adherence is supervised and monitored, and by optimizing antiretroviral treatment decisions, the effects of chronic viral hepatitis and methadone maintenance can be clarified to improve treatment in this and similar populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EVALUATION OF DIALECTICAL BEHAVIOR THERAPY (DBT) Principal Investigator & Institution: Linehan, Marsha M. Professor and Director; Psychology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2003; Project Start 20-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): The purpose of this proposal is to conduct an efficacy trial to determine whether Dialectical Behavior Therapy (DBT) added to suboxone (an opiate drug replacement) is an efficacious treatment for suicidal opiate addicts with Borderline Personality Disorder (BPD) characteristics and to analyze factors that influence efficacy in this population in order to improve the treatment. The combination of suicidality with substance abuse, particularly when other Axis I or II disorders are present, significantly compromises treatment outcome, and the purpose of this study is to investigate the efficacy of DBT added to suboxone as an effective treatment for this population. DBT, originally developed for chronically suicidal women with borderline personality disorder (BPD), is a synthesis of behavior therapy strategies aimed at change, and validation strategies aimed at acceptance, both held together by a set of dialectical strategies and underlying assumptions. DBT has been adapted for BPD substance abusers by the addition of 1) specific targets relevant to drug use, 2) a set of attachment strategies, 3) greater reliance on arbitrary reinforcers at treatment start, 4) weekly urinalysis, and 5) an opiate drug-replacement program (suboxone, i.e., buprenorphine in combination with naloxone) plus DBT clinical management. The research proposed here is a two arm, randomized clinical trial comparing a one year treatment program of DBT + suboxone for heroin addicted individuals to a one year program of Treatment-as-Usual (TAU) + suboxone. Treatment-as-usual will consist of the standard drug counseling and group therapies offered at area methadone clinics plus suboxone. Participants in both conditions will be prescribed psychotropic medications as needed. One hundred and thirty-six individuals (68 per condition) with opiate dependence, high suicidality and meeting a minimum of four BPD criterion will
48 Methadone
be enrolled in a one-year treatment and a one-year follow-up assessment. Assessments measuring drug use, suicidal behaviors, retention and other treatment-related behaviors, general psychopathology, and increases in behavioral skills will be given at four month intervals for the entire two years. Results will be analyzed using HLM and other regression-based procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL NEUROMAGING OF CUE-INDUCED HEROIN CRAVING Principal Investigator & Institution: Langleben, Daniel D. Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This is an application for a Mentored PatientOriented Research Career Development Award (K23) entitled "Functional neuroimaging of cue-induced heroin craving". The candidate's previous training and experience was in clinical psychiatry and nuclear medicine. Through this proposal, the candidate seeks to gain advanced training in: (1) functional magnetic resonance imaging (fMRI) and cognitive neuroscience methodology relevant to addiction research; (2) clinical research design and analysis, with a special emphasis on advanced statistical analysis of fMRI data and power analyses. The research project that is designed to complement this training program will use fMRI and experimental psychology methods to investigate the regional cerebral blood flow (CBF) changes during drug craving induced by heroinrelated cues to identify the brain networks mediating opiate craving. Studies by the investigators at candidates' laboratory and institution laid out the principles of drugrelated conditioned response in opiate-dependent patients and of Arterial Spin Labeling (perfusion) fMRI. Perfusion fMRI is particularly well suited for imaging of relatively prolonged states (e.g. cue-induced craving) and protocols involving repeated withinsubject experiments separated by days or weeks, such as the study of chronic medication effects. The candidate has extensive experience in the management of opiate dependence. An on-going pilot study by the candidate suggests an association between activation of the ventral tegmental area and heroin craving induced by opiate-related cues in methadone-maintained patients. The proposed project will expand and elaborate upon the previous findings and technological developments. Specific Aim 1 is to use fMRI to characterize the pattern of CBF response to cue-induced heroin craving and determine the specificity of this pattern in opiate-dependent subjects, building on the pilot data obtained by the candidate. Specific Aim 2 is to determine whether the CBF response to opiate-related cues in methadone-maintained patients is modulated by the fluctuation in methadone plasma levels. Specific Aim 3 is to characterize the effect of the opiate antagonist naltrexone on the CBF response to opiate-related cues in abstinent formerly opiate-dependent patients. The research plan will help determine the role of specific brain structures that mediate cue-induced craving to opiates and potentially to other drugs abuse acting on the mesocorticolimbic reward system. This data would improve our understanding of the mechanisms underlying dependence, treatment resistance and relapse. Furthermore, it may point the way for the development of novel methods for evaluation of the efficacy of pharmacotherapies and individual treatment response prediction in drug dependence. Implementation of this training and research plan will help the candidate to become an independent investigator in the neuropsychiatry of addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: G PROTEIN COUPLED RECEPTOR TRAFFICKING AND OPIATE DRUGS Principal Investigator & Institution: Whistler, Jennifer L.; Ernest Gallo Clinic and Research Center 5858 Horton St, Ste 200 Emeryville, CA 94608 Timing: Fiscal Year 2003; Project Start 20-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): A fundamental question in addiction biology is why opiate alkaloid drugs such as morphine and heroin have a high liability for inducing tolerance and addiction while endorphins and enkephalins, the native peptide ligands for opioid receptors do not. Following activation by agonists, opioid receptors are regulated by multiple mechanisms. Of these regulatory mechanisms, rapid endocytosis of opioid receptors is of particular interest because it is differentially regulated by peptide agonists and alkaloid drugs. Specifically, endogenous opioid peptides and certain opiate drugs such as etorphine and methadone stimulate the rapid internalization of mu opioid receptors. Morphine however, strongly activates receptor signaling but fails to stimulate the rapid internalization of mu opioid receptors. Furthermore, following endocytosis, individual receptors can be sorted differentially between recycling endosomes and lysosomes. This sorting mechanism can contribute to receptor regulation in two ways that have opposing effects on cell signaling. First, endocytosis can serve as a mechanism for receptor resensitization by delivering internalized receptors to endosomes from where they are recycled to the plasma membrane in a fully active state. Second, rapid internalization can serve as a first step toward receptor downregulation by delivering the receptors to endosomes from which they are sent to lysosomes for degradation. Most membrane proteins are rapidly recycled, presumably by default, because membrane itself is recycled continuously. Therefore it is likely that membrane receptors that are rapidly degraded following their endocytosis do so through a specific targeting mechanism. The post-endocytic sorting of individual receptors between recycling and degradative fates is biochemically specific and appears to be highly regulated, identifying this sorting step as a fundamental mechanism that controls the degradative down-regulation of a large number of receptors relevant to neuropsychiatric research. Hence for each receptor/ligand pair, one must evaluate both the endocytic and post-endocytic properties. The specific aims outlined below are designed to elucidate the molecular basis for endocytosis and sorting of the opioid receptors and assess in a cell culture model what effects altered trafficking has on the development of tolerance and withdrawal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GABAERGIC & GLUTAMATERGIC AGENTS--COCAINE USE IN METHADONE MAINTENANCE Principal Investigator & Institution: George, Tony P. Assistant Professor of Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: This section of this Medications Development Unit (MDU) outlines phase ll screening studies for armacotherapy of cocaine use in methadone- maintained subjects with agents that act through GABAergic or lutamatergic mechanisms. These studies would be carried out in two parts, with GABAergic agents being tested in Years l-2, and glutamatergic agents in Years 3-5. Our group has a long history of completing pharmacotherapy trials in cocaine-using methadone subjects, and examples have included desipramine, mazindol, amantadine, bromocriptine and bupropion. Preclinical evidence indicates that GABA and glutamate systems can modulate dopamine
50 Methadone
reward pathways which are thought to underlie the addictive properties of cocaine, and agents which modulate GABA and glutamate systems can reduce the reinforcing properties of cocaine in animal models. The GABAergic agents chosen for these pilot studies are: l) the GABAB agonist baclofen; and 2) the selective GABA reuptake inhibitor tiagabine. The glutamatergic agents chosen for phase I studies are: l) the NMDA receptor antagonist acamprosate and 2) the pre~synaptic glutamate release inhibitor lamotrigine. A total of 60 subjects will be recruited into each study for a total of 120 subjects over the entire five year period. Subjects will be randomized to one of five cells: placebo or two different doses of either baclofen or tiagabine (Study 1) or acamprosate or lamotrigine (Study 2) for a total of 8 or 12 weeks of active treatment for GABAergic and glutamatergic agents respectively. At the end of the active trials, medications would be tapered over a two week period. Primary outcomes will be selfreported cocaine use, three times weekly urine toxicology for the cocaine metabolite benzoylecgonine and treatment retention. It is hoped that we will demonstrate the efficacy and safety one or more of these agents for cocaine use in opiate-maintained subjects, and if encouraging results are obtained, phase ll controlled studies would be planned with promising candidates identified from these phase ll screening trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENOME-WIDE ANALYSIS FOR ADDICTION SUSCEPTIBILITY GENES Principal Investigator & Institution: Lachman, Herbert M. Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 28-FEB-2006 Summary: (adapted from applicant's abstract): This is an R01 application for funding to identify chromosomal markers linked to drug dependence. The use of illicit, highly addictive drugs is a major public health and legal problem in the United States and around the world. There is an urgent need for new pharmacological treatment options. Since a substantial fraction of the vulnerability to abuse drugs has a genetic basis, determining underlying genetic factors will help identify new targets to therapeutic intervention. One approach used to identify genetic factors in complex traits is to use non-parametric linkage analysis, such as the affected sib pair method. However, it is very difficult to ascertain large numbers of sib pairs concordant for drug abuse/dependence, especially in subjects who are actively abusing hard drugs. The investigators will address this problem by ascertaining a relatively stable group of opiate dependent subjects and their affected siblings in a very large population of methadone maintenance clients. Opiate addicts enrolled in methadone programs are perhaps the most stable group of heavily addicted individuals available for clinical study, since they come to clinic almost every day to pick up methadone, and meet with counselors, social workers, psychiatrists and medical doctors frequently. From a pool of 20,000 clients, they will identify 450 sib pairs who are both being treated in a methadone program. These subjects will be assessed by SCID and various psychological measures to identify psychiatric conditions and personality and temperament traits associated with substance dependence. A two stage, genome-wide search for genetic loci linked to opiate dependence will take place; the first at a 10 centimorgan resolution. Positive markers will be followed up in a second stage, 1-3 centimorgan survey. By the end of the project, which will coincide with the completion of the human genome project, they will be able to analyze all of the specific candidate genes that map to linked markers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GESTATIONAL BUPRENORPHINE & MESOLIMBIC SYSTEMS ONTOGENY Principal Investigator & Institution: Coscia, Carmine J. Professor; Biochem and Molecular Biology; St. Louis University St. Louis, MO 63110 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2004 Summary: (provided by applicant): Heroin abuse has increased significantly in recent years especially among the young. The statistics emphasize the need for new approaches to the treatment of maternal heroin abuse. Currently, the only drug approved for treating opiate dependence in pregnant U.S. women is methodone. Successful clinical trials suggest that buprenorphine will soon become a useful addition to the armamentarium of heroine addiction pharmacotherapy. Buprenorphine is an opiate alkaloid that acts as a mu opiate partial agonist, a nociceptin/orphanin receptor full agonist and a kappa antagonist. In comparison to methadone, buprenorphine has a lower abuse liability, a longer lasting action, a less intense withdrawal state and less physical dependence. Our previous findings demonstrate that in utero buprenorphine administration induces mu and kappa opioid receptor adaptation in developing rat brain. By acting at mu, kappa and nociceptin/orphanin receptors, buprenorphine may exert a blockade of mesolimbic reward mechanisms, thereby accounting for its ability to antagonize the reinforcing effects of heroine. Our focus will be to test the hypothesis that gestational opiates induce changes in opioid receptor binding density, phosphorylation and G protein coupling, an estimate of signaling capacity, thereby altering opioid receptor function in mesolimbic regions of offspring. We will determine whether correlative changes occur to these 3 signaling parameters. Discrete mesolimbic structures of developing rats exposed to gestational buprenorphine plu and minus naloxone will be compared to those treated with methadone and heroine. There are 3 specific aims: AIM 1. Measure gestational buprenorphine-induced opioid receptor adaptation in mesolimbic brain regions of developing offspring and dams by receptor autoradiography and semi-quantitative immunofluorescence confocal microscopy. AIM 2. Measure buprenorphine-induced mu opioid receptor phosphorylation in selected mesolimbic brain regions of developing offspring and dams by immunoblotting. AIM 3. Measure changes in mesolimbic opioid receptor activation of G proteins induced by gestational buprenorphine. This is an exploratory/developmental grant proposal (R21) to develop semi-quantitative immunological and autoradiographic techniques with anatomical and cellular resolution in neonatal mesolimbic brain regions. They will be used to determine whether gestational opiate exposure alters opioid receptor adaptation, receptor phosphorylation and/or coupling to G proteins in the mesolimbic regions of offspring brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GHB ABUSE: MOTIVATIONS, MEDICAL CONSEQUENCES, & RISKS Principal Investigator & Institution: Dyer, Jo E. Clinical Pharmacy; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002; Project Start 25-MAY-2002; Project End 30-APR-2007 Summary: BACKGROUND: Gamma hydroxybutyrate (GHB) and its precursors (GHBP) are major causes of drug-related coma in the U.S. Dramatic and rapid changes in patterns of GHB use are associated with increasing morbidity and mortality. Despite this, little is known about the determinants of adverse outcomes following use. STUDY HYPOTHESIS: Adverse outcomes following GHB use are multi- factorial. We propose
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to delineate the role of psychosocial and physical factors as predictors of adverse outcomes in GHB use; including socio-demographic factors, attitudinal issues, specific exposures (GHB v. GHB-P), and pharmaco-dynamics. EXPERIMENTAL PLAN: Component C1: California Poison Control System (CPCS) surveillance will capture demographics, exposure, and outcomes for 600 exposure subjects over the study period. Product and blood/urine testing will confirm GHB or its precursors. Component C2: Structured interviews of 390 exposed subjects, recruited from the CPCS surveillance cohort, will collect supplemental data not available from passive surveillance alone. Component C3: Controlled human exposures in 144 volunteers will compare disposition kinetics and effects of GHB and 1,4 butanediol, examining dose-dependence, gender differences, ethnic differences, genetic influences and interaction with ethanol. Component C4: Focus groups will explore the motivating factors for GHB use and abuse. Nine focus groups (54 subjects) from 3 sources (an adverse experience group from C2; experimentally exposed subjects from C3; and a community-based sample of GHB users without adverse events) will evaluate differences in hazard perception, acquisition, settings and use outcomes. Analyse s: Multivariate modeling will have sufficient power to detect RR's less than 2.0 for key risk factors and outcomes in the 20 percent incidence range. Human exposures will use paired and repeated-measures comparisons with power to detect change slightly greater than one standard deviation. SIGNIFICANCE: This study, by elucidating predictors of adverse outcomes from GHB use will provide data important for clinical and public health interventions to reduce morbidity associated with this drug of abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTAMATERGIC SYSTEMS IN PAIN AND OPIOID ACTION Principal Investigator & Institution: Inturrisi, Charles E. Professor; Pharmacology; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-MAY-1976; Project End 29-FEB-2004 Summary: (adapted from the applicant's abstract) This is a request for continued support of projects designed to test the hypothesis that Excitatory Amino Acid (EAA) receptors mediate the neuronal plasticity that is manifest as opioid tolerance and dependence or as certain types of nociceptive behavior. These studies will use NMDA and non-NMDA receptor antagonists as well as antisense targeted to NMDA receptors in selected animal behavioral paradigms to demonstrate the role of EAA receptors in opioid tolerance and nociception. These antagonists include the open channel blockers, dextromethorphan, and the d and 1 isomers of methadone and newer antagonists acting at the glycine site, the NR2B subunit of NMDAR1 or the GluR5 subunit of non-NMDA receptors. Antisense oligos will be targeted to the NR1, NR2B and GluR5 subunits. To complement and extend these approaches, opioid tolerance, dependence and nociceptive behaviors will be measured in knockout mice engineered with an absent or mutated EAA receptor. A strategy is presented for the production of the first conditional knockout of the NR1 subunit that is confined to the dorsal horn of the spinal cord. Molecular and biochemical techniques including receptor binding, autoradiography, subunit specific ribonuclease protection assays and immunocytochemistry will be used to identify and localize to neuroanatomical areas, the changes in gene expression that are associated with these altered behaviors. Nociception, opioid tolerance and dependence are complex phenomena involving the alterations in integrated neuronal circuits (between systems events) as well as plasticity changes expressed in individual neurons. They appear to share a common locus, the EEA receptor system. An
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understanding of this system is important for the development of new and more selective drugs for the management of pain and opioid abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GONADAL HORMONES ON BODY COMPOSITION, HIV AND DRUG USE Principal Investigator & Institution: Dobs, Adrian S. Professor of Medicine and Oncology; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 25-DEC-1999; Project End 30-NOV-2002 Summary: Metabolic and endocrine abnormalities are well-described in HIV- infected men and women. Several findings indicate a possible influence of sex hormone levels on AIDS progression. These include 1) the relationship of deceased serum sex hormone levels to HIV-associated wasting, 2) the possible benefits of testosterone replacement therapy on body composition, 3) the recent observation that men and women have varying levels of HIV- viral loads. The mechanisms of sex hormone deficiency in HIVinfected men and women may relate to the combined effects of chronic illness, undernutrition and a complex regimen of medications. Injection drug users (IDU), with or without co- existing HIV infection, may be susceptible to similar metabolic abnormalities, however little is known of the hormonal milieu of this cohort in which an estimated 50 percent of new HIV infections occur. Improved understanding of the overall health status of the IDU may enhance the effectiveness of the relative cures already available to the IDU and subsequently increase control of the AIDS epidemic in this cohort. We hypothesize that male and female IDU are predisposed to endocrine abnormalities, such as hypogonadism, which leads to reductions in lean body mass and quality of life (QOL), and that treatment of male hypogonadism with testosterone improves these parameters. Our overall goal is to understand the effects of IDU and HIV on the hormonal milieu. In a population of men and women, stratified by IDU and HIV status, our specific aims are: 1) To document gonadal function, 2) To determine the relationship of sex steroids to body composition, 3) To ascertain a prevalence estimate of the lipodystropy/metabolic syndrome (as defined in the grant), and 4) To evaluate the safety and efficacy of testosterone replacement therapy on QOL and body composition in men, stratified by HIV status, who have agreed to accept methadone treatment. We propose two clinical experiments: Study A is a cross-sectional study of heroin and/or cocaine dependent men and women, stratified by HIV status to evaluate their hormonal milieu and body composition. Study B is a randomized, placebo-controlled, clinical trial in which men with low serum testosterone levels on chronic methadone will be treated with active or placebo testosterone. Our outcome measures are serum hormones, body composition, muscle strength, and QOL. In summary, we intend to characterize the effects of HIV and IDU on the metabolic/endocrine system in men and women and to perform a clinical trial using testosterone replacement therapy in men. These studies can provide information to further our understanding of gender differences in disease progression and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HAIR ANALYSIS TO MONITOR DRUG ABUSE TREATMENTS Principal Investigator & Institution: Wilkins, Diana G. Assistant Director; Pharmacology and Toxicology; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2004
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Summary: (Applicant's Abstract) Improved methods to monitor treatment compliance and efficacy is an important goal of drug-abuse treatment programs and clinical trials for new treatment regimens. Monitoring drug use during pregnancy is also an important clinical goal. Compared to urine, plasma and blood, hair may provide a longer window to monitor for drugs and other compounds due to its slow growth and possible permanent retention of drugs. The presence of certain drugs and their metabolites has been demonstrated in human hair at times when plasma and urine drug concentrations are not measurable. The goal of this project is to acquire knowledge regarding the suitability of quantitative, segmental human hair analysis for determination of drug exposure in clinical settings. Specific marker substances will be used to establish reference points (with respect to time) in human hair. To achieve these objectives, the following specific aims are proposed: (1) To develop quantitative analytical methods for hair utilizing LC/MS/MS. Ultra-sensitive and specific procedures using liquid chromatography and tandem mass spectrometry will be developed for the combined detection and quantitation of a treatment drug (buprenorphine, 1-alpha-acetylmethadol, or methadone), drugs of abuse (morphine, heroin) and marker substances (phenazopyridine or ofloxacin) in hair. Also, specific and selective decontamination procedures will be developed to minimize the potential bias of environmental contamination of hair for drugs of interest and to maximize the reliability of measured quantitative drug concentrations. (2) To determine if quantitative analysis of hair can be used to evaluate recidivism and treatment compliance. Administration of a marker substance such as phenazopyridine or ofloxacin will be used to establish reference points in human hair between which drug use and treatment compliance or recidivism in clinical drug-abuse studies can be measured. We will also determine if quantitative measures of drug concentrations in hair are dependent upon the dose and route of drug administration. (3) To determine if quantitative analysis of hair can be used to evaluate fetal drug exposure in pregnant women receiving drug treatment. Specifically, we will determine if there is a relationship between maternal exposure to a treatment drug (methadone) during pregnancy and neonatal hair concentrations of methadone at birth. Preliminary data presented demonstrate that we are able to perform all aspects of this proposal and that we will clearly be able to progress from analytical methods development, to decontamination studies, to in vivo human and animal studies of marker substance incorporation into hair, and to studies of fetal drug exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HCV STABILIZATION
TREATMENT
OF
IDUS
AFTER
BUPRENORPHINE
Principal Investigator & Institution: Sylvestre, Diana L.; O.A.S.I.S. 2862 Telegraph Ave Oakland, CA 94609 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Approximately 60% of the nearly 40,000 new cases of hepatitis C (HCV) in the US each year are related to injection drug use (IDU), and IDU is the risk factor for 60% of the 4 million Americans exposed to this virus. The Urban Health Study (UHS) has found that 85-99% of street-recruited IDUs in the San Francisco area have been exposed to HCV. About 75-85% of those exposed will develop chronic hepatitis and are infectious to others, and at least 20% will develop cirrhosis after 2-3 decades. Although IDUs are the risk group most affected by HCV, they are the least likely to be offered HCV treatment due to concerns about medication adherence, side effects, and reinfection. For the past several years, Dr. Sylvestre and her colleagues
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at OASIS (Organization to Achieve Solutions in Substance-Abuse) have successfully treated nearly 100 methadone patients for HCV using a unique group treatment model that provides ongoing psychological and social support. Dr. Sylvestre has demonstrated that end-of-treatment response (ETR) rates are not significantly different from nonopioid-dependent populations. Drawing on their expertise collecting and analyzing epidemiological data and achieving adherence among HCV+ IDUs, Drs. Karen Seal and Brian Edlin of the Urban Health Study will collaborate with OASIS to extend HCV treatment to street-recruited active IDUs. This pilot feasibility study will use buprenorphine, a new medication for outpatient opioid treatment, to link IDUs to HCV therapy. Active heroin addicts with HCV will be identified through outreach, and after 12-24 weeks of buprenorphine stabilization, compliant participants will undergo pegylated interferon/ribavirin combination therapy while being maintained on buprenorphine. Specifically, in 50 street-recruited heroin injectors stabilized on buprenorphine and undergoing treatment for HCV, this observational feasibility study will describe: 1) the safety, side effects, and dropout rate of pegylated interferon/ribavirin treatment, 2) the adherence to HCV treatment in IDUs as measured by directly observed interferon injections and pill counts, and 3) ETR and sustained virologic responses to HCV treatment. Investigating the feasibility of combined outpatient substance abuse and HCV treatment for active street-recruitedIDUs represents an important step forward in the treatment of HCV and has the promise to decrease the enormous burden of this disease as well as prevent ongoing HCV transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HCV, HIV AND OPIOIDS: CELLULAR INTERACTIONS Principal Investigator & Institution: Ho, Wenzhe; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): This is a R21 application in response to RFA-DA-02008. Injection drug users (IDUs) are the single largest risk group for hepatitis C virus (HCV) infection and the co-infections with human immunodeficiency virus (HIV) and HCV are frequently found in IDUs. These two pathogens are also likely to be responsible for the highest infectious disease morbidity and mortality rates among IDUs. The general aim of this study is to determine the role of opioids (e.g., morphine) in the immunopathogenesis of HCV disease in the presence or absence of HIV infection. We hypothesize that opioids, through their receptors on human hepatocytes and immune cells, modulates HCV infection and replication. We will use both in vitro and in vivo models to directly address the question whether opioids have the ability to enhance HCV infection and replication. We seek to understand how HCV and HIV modify each other's replication in both in vitro and in vivo systems. We propose four specific aims: 1) We will determine whether opioids such as morphine enhances HCV infection of and replication in primary human hepatocytes, hepatoma cell lines (HepG2, Huh-7) and T cell lines (MT-2 and MT-2C); 2) We will determine whether opioids have the ability to induce HCV RNA expression in HCV replicon containing human hepatoma cell lines (Huh.5 and Huh.8). We will also examine whether HCV has ability to infect chronically HIV infected human T and monocytic cell lines (ACH-2, J 1.1 and U 1); 3) We will determine whether the removal of CD8+ T cells from PBMCs, and opioids, when added to CD8+ T cell-depleted PBMC isolated from HCV and/or HIV-infected subjects, induce HCV replication. In addition, we will examine whether HIV induces HCV replication in PBMCs isolated from HCV/HIV coinfected subjects; 4) We will determine plasma and
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PBMC HCV RNA levels in HCV and/or HIV-infected subjects attending methadone program. We will directly measure the levels of HCV RNA in plasma and PBMC using our newly developed real time RT-PCR assay. The investigation of the impact of opioids on HCV infection and its interaction with HIV will contribute to our basic understanding of host defense processes and the role of drug abuse in HCV and/or HIV infection of human liver and immune cells, ultimately further the design and development of improved treatment for drug-abusing patients infected with HCV and/or HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEROIN REINFORCEMENT DURING METHADONE TREATMENT Principal Investigator & Institution: Stitzer, Maxine L. Professor of Behavioral Biology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: Despite methadone's documented efficacy in achieving good treatment outcomes, many methadone maintained patients continue to use heroin during treatment. The goal of this component is to examine effects of i.v. heroin in patients maintained on methadone as well as interactions between methadone, cocaine and heroin in order to better understand the mechanisms that may underlie the continued use of heroin during methadone treatment. Four studies are proposed that utilize methods of the human behavioral pharmacology laboratory to perform systematic parametric investigations under controlled conditions. Study 1 examines reinforcing properties of i.v. heroin challenges, as indexed by subjective measures, at three methadone maintenance doses (30, 60, 120 mg/day) that include and surpass the range of doses in common clinical use and at three post-methadone dosing intervals (4, 28, 52 hours) that correspond to use of heroin on the same day as methadone is taken, on the following day prior to the scheduled methadone dose and following a missed methadone dose. Study 2 replicates and extends the results of study 1 by examining heroin's reinforcing properties, as indexed by i.v. heroin self-administration, at these same methadone maintenance doses. Study 3 determine whether use of heroin during methadone treatment engenders increased levels of physical dependence that must then be suppressed through additional heroin use. Signs and symptoms of physical dependence will be evaluated using both precipitated and spontaneous withdrawal methods in methadone maintained volunteers who are concurrently exposed to varying amounts of i.v. heroin use, under conditions that simulate patterns of supplemental heroin use in the natural environment. The use of heroin during methadone treatment is strongly associated with use of cocaine. Study 4 use subjective report methods to examine the reinforcing properties of heroin alone, cocaine alone and heroin-cocaine combinations in patients maintained on three methadone doses (30, 60, 120 mg/day). The aim is to determine whether and how cocaine's effects are modulated by concurrent use with heroin during methadone treatment. These four studies will provide empirical data on how various methadone doses influence the reinforcing properties of heroin when used alone or in combination with cocaine and will also illuminate conditions under which concurrent use of heroin adds to the physical dependence engendered by methadone maintenance. These studies will identify potential mechanisms underlying the continued use of heroin during methadone treatment and, because of their parametric nature, should suggest optimal treatment doses for minimizing heroin selfadministration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIV PROTEASE INHIBITOR & METHADONE METABOLISM IN HIV Principal Investigator & Institution: Flexner, Charles W. Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: ACTG 401 is designed to study pharmacokinetic interactions of methadone and HIV protease inhibitors (ritonavir * saquinavir). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIV PROTEASE INHIBITORS AND METHADONE METABOLISM IN HIV+ SUBJECTS Principal Investigator & Institution: Jacobson, Mark A. Professor of Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIV RISK AND PARTNER VIOLENCE--MEN ON METHADONE Principal Investigator & Institution: El-Bassel, Nabila; Associate Professor; None; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027 Timing: Fiscal Year 2001; Project Start 20-FEB-1999; Project End 31-JAN-2003 Summary: Accumulating evidence links partner violence and HIV infection. Among the groups disproportionately affected by these trends are methadone patients. Estimated lifetime rates of partner violence reported by women in drug treatment programs range from 60% to 75%. Seroprevalance rates of HIV among methadone patients in East Coast urban areas range from 28% to 43%. Despite the high prevalence of partner violence and HIV among methadone patients and mounting evidence suggesting that partner violence and HIV-risk behaviors may be interrelated phenomena in this population, studies have yet to untangle the multi-dimensional relationship between these two critical public health problems. Moreover, as of yet, no empirical research has examined these relationships from the male perpetrator's perspective. Longitudinal data on the bidirectional relationships between the perpetration of partner violence and HIV-risk behaviors among men on methadone may address some of the major gaps in research. The proposed study will: 1) explore the relationship dynamics and sequences of events that culminate in the co- occurrence of inflicting partner violence and engaging in HIVrisk behaviors among men who are enrolled in methadone maintenance treatment programs (MMTPs) using in-depth qualitative methods; and 2) examine longitudinally the relationships between the perpetration of partner violence and HIV-risk behaviors among men in MMTPs, controlling for background variables and risk factors (e.g., drug use, communications, prevalence of violence in perpetrator's social network). In the beginning of the first year, men attending MMTPs who report perpetrating partner violence in the past year will participate in focus groups (n=64) and in-depth interviews (n=50) for the longitudinal study that will begin in the second year, 600 men will be interviewed at baseline and at six and twelve month follow-ups. At the completion of the longitudinal study, two focus groups will be conducted with 16 men who report perpetrating partner violence in the part year, to elicit their interpretation of the quantitative research findings. Subjects will be recruited from Beth Israel Medical Center
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methadone clinics in Harlem. This study will be led by investigators from the Social Intervention Group (SIG) at Columbia University School of Social Work and Beth Israel Medical Center. Data from the proposed study will help inform assessment, treatment and referral protocols to reduce partner violence and HIV-risk behaviors among men and women in MMTPs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOME NURSE INTERVENTION OF IUDE INFANTS: 3 YEAR FOLLOW UP Principal Investigator & Institution: Butz, Arlene;; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: Each year in the U.S. approximately 220,000 infants are born to mothers who used illicit drugs during pregnancy. Others report between 4-10% of all pregnant women have used cocaine. There is growing evidence that in utero drug exposure (IUDE) to cocaine constitutes a risk leading to long-term alterations of brain functioning. Long term follow-up studies of opiate exposed children indicate that although intellectual deficits may be mild or nonexistent, behavioral abnormalities may persists into the school years. One major difficulty in studying opiate exposed children is determining which factors (environmental or direct effects or opiate exposure) result in the poor outcomes. Foster care placement for IUDE children is high. Almost half (43%) of opiate exposed children were removed from the biological parent in one longitudinal study. Cost burden of drug exposed infants are a direct result of the high incidence of prematurity, low birthweight and neonatal drug withdrawal symptoms. Neonatal drug withdrawal occurs in 42-68% in heroin addicted and 63-85% of methadone addicted newborns contributing to an increased length of stay. Other cost burdens are difficult to measure including the effects on the development and performance of the individual over a lifetime Early intervention programs including home nurse interventions are thought to enhance parenting to enrich the development in biologically and environmentally challenged infants. The goal of this continuation study is to determine if a Pediatric Nurse Specialist (PNS) home intervention will be associated with sustained effects of improved child health and demonstrate cost effectiveness in the 204 enrolled in utero drug exposed infants up to age 5 years. Additionally, the goal is to compare the intervention children to a group of non-drug-exposed control infants of comparable environment/ socioeconomic status. This ongoing study is a randomized, two-group, repeated measures controlled clinical trial to test the effectiveness of a home-based PNS intervention. Infants were randomized into the PNS intervention (N=100) or control (N=100) groups. All 204 IUDE infants were born at the Johns Hopkins Hospital and had documented IUDE based on maternal drug history by review of prenatal records and maternal urine toxicology screens at delivery and/or infant urine toxicology screens obtained within 24 hours of birth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HPA IMMUNE RESPONSE TO MORPHINE IN CHRONIC OPIOID MAINTENANCE Principal Investigator & Institution: Compton, Peggy;; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001 Summary: This abstract is not available.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN METABOLISM OF ANTI-ABUSE MEDICATIONS Principal Investigator & Institution: Moody, David E. Associate Director; Pharmacology and Toxicology; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2006 Summary: (provided by applicant): Buprenorphine is a partial mu agonist under consideration by the FDA for use in opioid substitution therapy. It will join methadone and I-alpha-acetylmethadol (LAAM) as medications available at treatment centers. Buprenorphine is also being considered for private physician dispersal; which will greatly expand access to substitution therapy. All three of these drugs are cytochrome P450 (P450) 3A4 substrates. Drug interactions are a major cause of serious adverse drug effects and P450 3A4 is a major site of drug interactions. Many known drug interactions with methadone are due to its metabolism by P450 3A4. The proposal funded during the last period (R01 DA 10100-02) tested the hypothesis that the 3A4 inhibitor, ketoconazole, would inhibit the metabolism of LAAM to its more active metabolites, norLAAM and dinorLAAM, and thereby diminish its therapeutic effect. Data from that study demonstrate both in vitro and in vivo evidence of significant drug interactions providing support for this hypothesis. Since buprenorphine is nearing market launch, and few studies exist on its potential for serious drug interactions, we now hypothesize that determination of enzymes involved in the in vitro hepatic metabolism of buprenorphine will allow prediction of in vivo drug interactions of clinical significance. While testing this hypothesis, the fact that buprenorphine and its metabolite, norbuprenorphine, are extensively glucuronidated, and preliminary data that suggest other metabolites are produced by P450s must be taken into consideration. Therefore, to test this hypothesis we will: 1) extend our current liquid chromatographic-tandem mass spectrometric (LC-MSMS) method for buprenorphine and norbuprenorphine to include their glururonides; 2) use LC-MSMS to identify metabolites of buprenorphine generated in human liver microsomes (HLM) and cDNA-expressed P450s; 3) determine the quantitative involvement of specific P450s in these pathways using kinetic analyses, specific inhibitors, specific antibodies and correlational analysis in HILM and cDNAexpressed P450s; determine the qualitative involvement of specific UDP-glucuronosyl transferases (UGTs) using HILM and cDNA-expressed UGTs; and 4) determine the in vitro induction of buprenorphine phase I and phase II metabolism in primary cultures of human hepatocytes. We anticipate these studies will provide the evidence to support clinical studies to more thoroughly test our hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN POLYDRUG USE: AND ECONOMIC ANALYSIS Principal Investigator & Institution: Spiga, Ralph; Psychological Studies in Educ; Temple University 406 Usb, 083-45 Philadelphia, PA 19122 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: Polydrug abuse is a common pattern of drug abuse which involves simultaneous or sequential use of multiple drugs. From an economic perspective drugs are commodities, the drug user is a consumer, drugs of abuse have a price, and drug consumption varies with price. Thus, behavioral economic concepts such as unit price, elasticity, and demand may be useful in determining drug use patterns in polydrug environments. These studies will (1) investigate human drug choices in a controlled polydrug laboratory environment and (2) determine whether behavioral economic
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concepts describe the observed patterns of drug consumption. In each study participants will be randomly assigned to GROUP 1: PRIMARY DRUG VS VEHICLE ALTERNATIVE or GROUP 2: PRIMARY DRUG VS DRUG ALTERNATIVE. Participants in GROUP 1 will have the option of procuring small doses of drug or vehicle by pressing a button. Their counterparts in GROUP 2 will have the option of procuring either of two concurrently available drugs. STUDY 1 will examine methadone consumption when vehicle (GROUP 1) or ethanol (GROUP 2) are concurrently available. STUDY 2 will examine methadone consumption when vehicle and hydromorphone are the concurrent drug alternatives. STUDY 3 will examine intranasal cocaine consumption when vehicle or oral cocaine are the concurrent drug alternatives. STUDY 4 will examine intranasal cocaine consumption when vehicle or ethanol are the concurrent drug alternatives. Price for procuring drug will be increased systematically for participants in both experimental groups. This permits determination of demand curves, elasticity of demand, and cross-price elasticity. Demand will be assessed by observing the effect of price increases of primary drug on primary drug consumption when vehicle is concurrently available (GROUP 1). Elasticity will be assessed by comparing primary drug consumption across price in the presence vehicle or alternative drug (comparison of GROUP 1 and 2). Cross-price elasticity will be assessed by observing the effects of primary drug price on consumption of alternative drug (GROUP 2). These studies will collect economic data on polydrug abuse, test behavioral economic concepts of drug choice, and extend economic principles to the understanding and control of polydrug abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERALGESIA IN METHADONE PATIENTS: CAN IT BE TREATED? Principal Investigator & Institution: Compton, Margaret A. None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states
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suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IATROGENIC OPIOID DEPENDENCE IN CRITICALLY ILL CHILDREN Principal Investigator & Institution: Lugo, Ralph A. Pharmacy Practice; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: (Applicant's Abstract) Critically ill children in the pediatric intensive care unit often require long-term sedation and analgesia. Fentanyl has a rapid onset, short duration of action, and stable hemodynamic profile. Thus, it is the most desirable opioid for continuous analgesia and sedation in the pediatric intensive care unit. However, continuous administration of fentanyl often leads to rapid development of tolerance, progressive dose escalations, and ultimately iatrogenic opioid dependence. Discontinuation of fentanyl in these children will precipitate acute abstinence syndrome which may compromise the care of the child. Currently, it is not fully understood which patients are at risk for opioid dependence and withdrawal, nor is there a validated method of objectively assessing the severity of withdrawal. Although the optimal treatment of iatrogenic opioid abstinence syndrome has not been established in critically ill children, oral methadone is often used to facilitate fentanyl discontinuation while preventing signs and symptoms of withdrawal. However, no data are available regarding the optimal dose or pharmacokinetics of methadone in this patient population. This proposal aims to generate data on wide ranging aspects of iatrogenic fentanyl dependence, including diagnosis and evaluation of its severity, determination of risk factors for its development, and the pharmacokinetics of fentanyl and methadone in critically ill children. The specific aims of these studies are: 1) to validate a clinical scoring tool to be used by the bedside nurse to objectively measure the severity of iatrogenic fentanyl abstinence syndrome. This scoring tool may be used to determine when treatment of fentanyl withdrawal is necessary; 2) to quantitate fentanyl exposure by measuring fentanyl's cumulative area under the concentration-time curve; 3) to evaluate the relationship between systemic fentanyl exposure and the risk of iatrogenic opioid abstinence syndrome; and 4) to define the pharmacokinetics and bioavailability of methadone which is used to treat fentanyl withdrawal in these critically ill children. These data will significantly augment our understanding of opioid withdrawal in critically ill children and increase our knowledge of fentanyl and methadone pharmacokinetics, both of which are critical in safely administering these agents to children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMIPRAMINE METHADONE PTS
RELAPSE
PREVENTION
IN
DEPRESSED
Principal Investigator & Institution: Tross, Susan; Psychologist; St. Luke's Roosevelt Hosp Ctr (New York) 1111 Amsterdam Ave New York, NY 10025 Timing: Fiscal Year 1999; Project Start 01-SEP-1996; Project End 30-JUN-2004 Summary: APPLICANT'S ABSTRACT: This is a revised version of the previously submitted application, #ROI DA09583-01, also entitled Imipramine+Relapse Prevention in Depressed Methadone Pts. Relapse prevention is a widely used cognitive-behavioral skills training approach to the problem of initiating and maintaining drug use abstinence. Imipramine has been shown to have strong antidepressant effects and significant, but qualified, effects on self-reported drug use among depressed cocaineusing methadone patients. Among this substantial subgroup of patients, there are no studies of the efficacy of combination pharmacotherapeutic and psychotherapeutic approaches to the problem of cocaine use. This study will examine the question of whether adding relapse prevention group to imipramine is more effective than imipramine alone in reducing cocaine use among 252 inner-city depressed methadone patients who use cocaine. It will have the methodological advantages of: (1) including a non-specific psychological intervention comparison condition (i.e. support group); and (2) targeting a sample with rigorously diagnosed DSM-IV depressive disorders. It will have the important clinical advantage of using a manualdriven relapse prevention protocol -- that will draw from two programs with demonstrated efficacy. This study will also assess the impact of potential predictors on intervention effects on cocaine use, especially severity of cocaine use and severity of depression. It will also assess the impact of potential mediators, representing acquisition of intervention components, on intervention effects on cocaine use, especially: level of relapse prevention skill and perceived self-efficacy to use these skills. Patients will be assessed on repeated measures of cocaine use and depression at: baseline, end of psychological intervention (at 3 months), end of imipramine maintenance (at 6 months) and 3-month post-intervention follow-up (at 9 months). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF FINANCING ON OUTCOMES OF METHADONE MAINTENANCE Principal Investigator & Institution: Deck, Dennis D.; Rmc Research Corporation 1000 Market St Portsmouth, NH 03801 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): This study examines the outcomes of publicly funded methadone maintenance programs treating opiate dependence in Oregon and Washington, two states that include methadone maintenance services in the Medicaid benefit but important differences in financing that have strongly influenced provider practices. We hypothesize that opiate users presenting for treatment in Oregon will have greater access to methadone than their Washington counterparts. Users of methadone maintenance services in Oregon will have greater retention in treatment and subsequently display fewer arrests, less reliance on public assistance, and reduced emergency room visits than their Washington counterparts. Difference in provider policies and practices resulting from both state differences in funding mechanisms will be associated with differences in client outcomes after controlling for client characteristics. The subjects will be Medicaid-eligible opiate users presenting for treatment in Oregon and Washington during 1992 through 2000. Client characteristics
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and outcomes for 3 years post-admission will be determined from administrative data sets, including statewide treatment databases, Medicaid eligibility files, Medicaid claims/encounter records, statewide arrest databases, quarterly wages, and vital statistics. Provider policies and practices (e.g., dosing and discharge) will be documented through interviews with all methadone providers in both states. A calendar-based protocol will be used to determine how long these have been in place. Our conceptual framework is adapted from Andersen's behavioral model where the use of treatment services and outcomes are a function of both client characteristics and system characteristics driving provider policies and practices. Multilevel analyses using hierarchical linear models (HLM) will be used to address both client and provider or systemic factors. Proximity to a methadone clinic is strongly related to access to methadone maintenance and will be used as an instrumental variable in some analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VITRO AND IN VIVO PHARMACOLOGY OF OPIOIDS Principal Investigator & Institution: Traynor, John R. Senior Associate Research Scientist; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: This project has three aims. 1. The characterization of opioids as Potential PET agents. 2. To develop an understanding of the molecular mechanisms behind potential treatment agents. 3. To characterize and provide novel opioid compounds in accordance with a major aim of the Center. Aim 1. We will identify selective agonists and antagonists with properties that make them suitable for labeling as PET agents for the visualization of mu, delta and kappa opioid receptors in monkey and in man. This involves close collaboration with the chemistry (Husbands, Project 1A) and radiochemistry (Kilbourn, Project 1B) components of the Center and with the potential end users (Winger, Project 4; Ko, Project 3 and Zubieta). Aim 2. Buprenorphine is a popular alternative as a medication for the treatment of heroin abuse. Methoclocinnamox is a lead compound we have developed as a longer lasting alternative. The mechanisms by which these drugs are beneficial in heroin addiction are not clear. For example, it could be their agonist action or their antagonist actions (or both) that are most important. Newer ideas concerning the cellular actions of morphine and related mu opioids includes agonist-specific states of the mu receptor that might activate different intracellular pathways and roles for receptor dimers and heterodimers. We will compare the cellular actions of buprenorphine and MCCAM and opioids that differ in their structure, efficacy or receptor kinetics using cells that express mu or mu and delta receptors and that we will express different Galpha subunits, or measure activation of different Galpha subunits. Acute opioid actions at different levels of the signaling cascade, and mechanisms contributing to tolerance development (phosphorylation, internalization and down-regulation) will be determined. In addition we will examine the effects of these agents in a cellular model of physiological dependence and withdrawal (adenylyl cyciase supersensitivity). We hope to uncover how these treatment agents differ from other opioids and, in conjunction with chemistry and modeling, provide clues for the design of safer and more effective agents. Aim 3. Seeks to identify and develop opioid compounds for the scientific and clinical community and to examine compounds submitted to the Drug Evaluation Committee of the College on Problems of Drug Dependence as part of their abuse liability evaluation. This is an important undertaking of the Center and provides a valuable service to government agencies and academia.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INCENTIVES TO IMPROVE TREATMENT OUTCOME IN HIV AND IDUS Principal Investigator & Institution: Batki, Steven L. Professor and Director of Research; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2002 Summary: (Applicant?s Abstract) The overall goal of the proposed research study is to improve treatment outcomes for drug use and medical care among human immunodeficiency virus (HIV) infected injection drug users (IDUs) undergoing methadone treatment. Methadone maintenance treatment (MMT) is a widely applied and highly effective treatment available for IDUs who are opioid dependent, yet it has limitations. For example, while methadone treatment significantly reduces the use of heroin, it does not completely eliminate opiate use in all patients. Furthermore, the use of non-opiates such as stimulants, alcohol, and other drugs is not as robustly reduced in MMT patients as is the use of opiates. Continued drug use by HIV-infected IDUs increase the risk for other infectious diseases. Drug use may also cause problems with HIV health care by interfering with appointment keeping and adherence to medical regimens. It is therefore essential to find ways to improve the effectiveness of MMT with respect to both drug use and medical care in HIV-infected persons. The proposed study will consist of a six month randomized trial to test the efficacy of incentives in the form of contingent vouchers designed to improve the treatment outcome of HIV-infected MMT patients in the domains of drug use and HIV medical care. 150 HIV-infected MMT patients will be randomized to one of three treatment conditions: 1) a Drug Voucher group that will be given incentives to reinforce drug-free urine tests, 2) a Drug plus Medical Voucher group that will be given incentives to reinforce both drug-free urines and HIV "Medical Care Management" appointment keeping, and 3) a No Voucher control group that will receive no incentives. Participants in the study will be able to exchange vouchers for goods and services of their choice. The main outcomes will consist of drug use, medical appointment keeping, HIV and drug-related medical morbidity, and HIV and drug-related health care costs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INCREASING DRUG USERS' ADHERENCE TO HIV THERAPEUTICS Principal Investigator & Institution: Broadhead, Robert S. Professor; Sociology; University of Connecticut Storrs Unit 1133 Storrs-Mansfield, CT 06269 Timing: Fiscal Year 2001; Project Start 25-DEC-1999; Project End 30-NOV-2003 Summary: HIV+ active and recovering drug users suffer from both poor utilization of, and low adherence to, primary care for HIV disease. Services that combine drug treatment and on-site primary care reduce these problems significantly because they create a support structure in which program staffs are able to monitor patients' health status, and give patients cues, reminders and reinforcement for keeping up with their treatments. However, only 10% to 15% of drug users are in drug treatment at any given time, and the vast majority of drug treatment programs do not provide primary care onsite. Thus only a small minority of drug users receive this demonstrably effective form of care. Hence, some alternative support structure is urgently needed for the large majority of HIV+ drug users who need help in obtaining and adhering to primary care services. This need is especially critical now that more effective antiretroviral therapy has become available with the advent of the protease inhibitors and potent combination
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regimens. Strict adherence to these regimens is essential, both for effectiveness and to prevent the emergence of HIV resistance. Studies of drug users' utilization of therapy outside of structured settings like methadone treatment programs -- suggest that as a group they are less likely to benefit from these new therapies and more likely than other populations to spread multidrug-resistant HIV to others through unprotected sex and/or the sharing of syringes. This project's aim is to evaluate an innovative approach, termed a Peer-Driven Intervention, that harnesses peer support among drug users to promote admission into primary care, adherence to HIV therapeutics and reduction of HIV-related behaviors. The feasibility of the approach has been demonstrated by a multi-year, MDA-funded HIV-prevention project for injection drug users (RO1 DA08014), directed by the PI of this proposal. The proposed project also grows out of a pilot study that demonstrates the viability of the approach as a means for increasing adherence to medical care among HIV+ drug users. We propose to recruit and randomly assign 300 HIV+ active and recovering drug users to two treatment conditions, a Peer- Driven Intervention and a Usual-Care Intervention, and compare their enrollment and retention in primary care services, adherence to HIV therapeutics, entry and retention in drug treatment, reduction of HIV risk behaviors, and increase in medical knowledge. The study site, New Haven, Connecticut, is especially well suited for this community-based study. It is a geographically compact city with a highly integrated health care system that has been heavily impacted by HIV. The project brings together a strong interdisciplinary team with extensive experience in studies of drug users, AIDS, drug treatment, and innovative health and prevention services. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFANT ATTACHMENT--MATERNAL TRAUMA AND DRUG USE Principal Investigator & Institution: Hans, Sydney L. Associate Professor; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2004 Summary: (Applicant's Abstract) The goal of this study is to better understand the nature of infant attachment to mothers who are drug using. Although previous research with small samples has suggested that children prenatally exposed to drugs are at risk for insecure and disorganized attachments, it remains unclear whether this risk derives from teratological or social factors. Such findings are of serious concern due to the close theoretical and empirical links that have been made between disorganized attachment and serious family pathology, including child maltreatment and adjustment problems. We propose to explore the following hypotheses: 1) that there will be an increased incidence of insecure and disorganized attachments in infants whose mothers have histories of serious substance abuse and 2) that the association between substance abuse and attachment can be accounted for by mothers' histories of exposure to trauma. In addition, we will examine the independent and mediating contributions to attachment of maternal dissociative symptoms, maternal resolution of attachment history, parenting behavior and beliefs, and infant temperament. The sample will include 200 12- to 18month-old infants and their mothers. Half of the mothers will be women with a history of heroin and other substance abuse, recruited form public methadone maintenance programs. Half of the mothers will be selected from a population of families presenting for pediatric care at a community health clinic. Infant attachment will be assessed form the Ainsworth Strange Situation using Main's supplemental disorganized attachment coding category. Maternal substance use and abuse, mental health, parenting, and infant temperament will be assessed using a multi-method approach. If hypotheses are confirmed, they would suggest the need for more comprehensive family interventions
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for women in substance abuse treatment that include parent-child relationship services, violence counseling, and adult mental health services. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INNOVATIVE JOB PLACEMENT MODEL FOR METHADONE PATIENTS Principal Investigator & Institution: Magura, Stephen; Acting Executive Director; National Development & Res Institutes Research Institutes, Inc. New York, NY 10010 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Abstract) Substance users in treatment programs, including methadone patients, historically have had poor rates of workforce participation. Nationally, 76 percent of methadone patients are unemployed at admission, with virtually the same rate at discharge. Traditionally, addicts in treatment have experienced substantial disincentives to enter employment because of the ready availability of public assistance, disability benefits for addiction disorders and Medicaid. However, policy changes are now creating a new environment. Recent federal and state welfare reform legislation (e.g., federal Personal Responsibility and Work Opportunity Reconciliation Act of 1996; New York State Welfare Reform Act of 1997) requires that drug treatment clients achieve work readiness in specific time frames or lose public benefits and other supports. There is evidence that most methadone patients are potentially capable of and interested in productive activity. However, few methadone programs have offered adequate vocational services. The proposed study will implement and evaluate an innovative vocational rehabilitation model to facilitate the transition of methadone patients from welfare to competitive employment. The specific aims are: 1) To implement and Individual Placement and Support Model for Substance Users (IPS-SU) among opiate addicts in methadone treatment. The innovative IPS vocational rehabilitation model was originally developed, manualized and favorably evaluated for a seriously mentally-ill (SMI) population. 2) To conduct a randomized field trail of the IPS-SU model's efficacy by voluntarily assigning unemployed methadone patients to either: (a) the innovative IPS-SU model (N=144), or (b) a traditional vocational services program (N=144). The primary outcomes, assessed at 6, 12, and 18 months after admission, are measures of competitive employment; the secondary outcomes are methadone program retention, substance use, and other measures of patient functioning. 3) To determine the static and dynamic patient attributes and intervention process variable which may predict differences in patient outcomes. 4) To conduct benefit-cost and cost-effectiveness analyses of the modified IPS vocational rehabilitation program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERSTITIAL CYSTITIS CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Payne, Christopher K. Associate Professor; Urology; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): This application proposes that Stanford University Center for Female Urology and NeuroUrology participate as one of several National Clinical Centers in a cooperative effort to develop clinical trials for the study of interstitial cystitis (IC). The Principal Investigator intends to participate fully as a member of the steering committee in designing and carrying out multicenter randomized controlled clinical trials (RCTs). The investigative group at Stanford will
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work in parallel with the centers conducting trials for investigation of chronic prostatitis. A simultaneous application for that effort is being submitted. This is a critical juncture for IC research. While appreciation of the prevalence and impact of the disease is growing, little headway has been made in identifying the underlying etiology or finding reliably effective treatment. More importantly, the very definition of IC and pelvic pain syndromes is under active debate--are all patients with pelvic pain simply varying manifestations of a single underlying disorder or are there important clinical distinctions between IC, vulvadynia, chronic prostatitis, and pelvic floor dysfunction? The relevance of standard diagnostic tools has been challenged. Bladder distention under anesthesia may be neither sensitive nor specific. Neither urodynamic testing nor bladder biopsy provides specific diagnostic information. A simple office trial of intravesical potassium instillation purported to identify IC totally failed to predict response to therapy in a RCT. These and other critical issues will only be settled by carefully designed, large scale RCTs. The ICCRN should focus on the following specific aims: 1) determining the clinical utility of currently diagnostic tests for IC and evaluating new tests 2) developing evidence based algorithms for the work-up of IC patients involved in clinical research 3) developing relevant clinical protocols that involve the entire spectrum of IC patients 4) to test novel therapies for IC as they become available. Stanford is ideally suited for this project due to a long history of interest in IC, a Principal Investigator with recognized expertise in clinical research, an ethnically diverse patient base, and demonstrable success recruiting patients for IC research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERVENTIONS FOR HIV-POSITIVE DRUG ABUSERS Principal Investigator & Institution: Avants, S K. Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2007 Summary: (Provided by Applicant): The goals of this application for an Independent Scientist Award (K02) are consistent with the strategic plan of the CDC for reducing HIV transmission in the years 2001 to 2006 through the development, evaluation, and dissemination of interventions targeted toward those persons already infected with HIV. HIV-infected drug users represent a major vector of HIV transmission not only through sharing of drug paraphernalia and unsafe sexual practices, but also in the context of nonadherence to HAART regimens, which can result in the emergence and transmission of medication-resistant strains of HIV. Interventions targeting this patient population would therefore have both individual and societal benefits. Communitybased substance abuse treatment programs have the potential to be highly instrumental in this regard. However, access to scientifically-evaluated, yet "user-friendly," manualguided interventions, together with comprehensive training on their provision, remains limited. The need exists for timely dissemination of results of research-based interventions for HIV-positive drug users to community settings in a format that is practical for use by clinicians in the field. This K02 application is being submitted subsequent to completion of a K21 award which permitted the applicant to become an independent researcher committed to addressing these issues. Goals are: (1) Intervention development. Develop interventions specifically targeting inner-city HIVpositive injection drug users to (a) reduce high risk behavior; (b) increase medication adherence, and (c) improve quality of life. (2) Intervention evaluation: Rigorously evaluate these interventions in randomized clinical trials that include cost analyses to ensure that these interventions are cost effective as well as clinically efficacious. (3)
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Technology transfer: Bring research findings to clinical practice by ensuring timely dissemination of efficacious and cost-effective treatments to community-based programs -- by publishing and disseminating treatment protocols in ready-to-use manuals, and by designing and implementing comprehensive training programs for front-line clinical staff using state-of-the-art technology in electronic and print communications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IV COCAINE ABUSE TREATMENT--A LABORATORY MODEL Principal Investigator & Institution: Foltin, Richard W. Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-JAN-1990; Project End 14-AUG-2002 Summary: (Applicant's Abstract) This protocol continues implementation of a laboratory model to evaluate pharmacological agents potentially useful in the treatment of cocaine abuse, investigating problems relevant to understanding and reducing uncontrolled cocaine use. It focuses on the smoked route, since crack use is now the major cocaine problem in the United States, and evaluates, within the context of cocaine self-administration, behavioral mechanisms of action of pharmacological agents proposed for treating cocaine dependence. Our approach is to explore several neurotransmitter systems, continuing to collect data on the basic biobehavioral mechanisms of cocaine's actions. Increasing evidence indicates that excitatory and inhibitory amino acid systems play a key role in the modulation of brain function and reward mechanisms. Vigabatrin and lamotrigine act on these modulatory amino acids. We will also test the selective DA autoreceptor antagonist UH 232, which, in laboratory animals, mimics some of cocaine's effects while antagonizing others, and the new antidepressant venlafaxine, which has shown promise in open-label clinical trials. Finally, we will test butorphanol, a partial mu and full kappa opioid receptor agonist, because kappa agonists attenuate many cocaine effects in laboratory animals, and because our laboratory found interesting effects with buprenorphine, the partial mu agonist and kappa antagonist. Our well-characterized laboratory model of cocaine abuse will be used to determine how potential treatment medications alter cocaine craving and the reinforcing, subjective, and cardiovascular effects of self-administered cocaine in non-treatment seeking cocaine users. Two groups of cocaine users will participate: methadone-maintained and non-methadone maintained. These studies will investigate the multiplicity of ways that a medication could enhance cocaine abstinence. The strength of this protocol lies in our utilization of a controlled laboratory setting to examine the interactive effects of potential treatment medications with the many facets of cocaine use, including cocaine "craving." The data collected will suggest more efficacious approaches to treating cocaine abusers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IV MNTX GUT EFFECT IN CHRONIC METHADONE THERAPY AND CHRONIC PAIN PATIENTS Principal Investigator & Institution: Yuan, Chun-Su;; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LABORATORY MODEL FOR HEROIN ABUSE MEDICATIONS Principal Investigator & Institution: Fischman, Marian W. Professor of Behavioral Biology; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001 Summary: Heroin use and treatment admissions for heroin dependence have been increasing steadily over the past several years. Clearly, there is a need for new effective treatments for opioid dependence. Although methadone, levo alpha-acetylmethadol (LAAM), and naltrexone are currently approved for the treatment of opioid dependence, many problems are associated with their use such as patient noncompliance, continued opioid use during treatment, and high relapse rates during withdrawal from treatment. Several possible causes for these problems have been suggested but insufficient research has been conducted to evaluate the effects of these medications on ongoing human behavior in a research laboratory setting. In the proposed research, participants residing in a controlled setting will be given the opportunity to work for heroin and money. These studies will examine the multiplicity of ways in which several current and proposed medications affect heroin consumption, performance, mood, physiological measures, and participants' verbal reports of drug effects. The model thus developed will be used to evaluate potential new medications for opioid abuse as they are developed and before they are put into large multi-center trials. The specific aims of the proposal are to evaluate: l) the effects of the combination tablet containing buprenorphine and naloxone; 2) the time course and efficacy of a depot formulation of naltrexone; 3) the ability of oral naltrexone maintenance to induce supersensitivity to the effects of heroin; and 4) the effects of memantine and dextromethorphan, which are low-affinity N-methyl-D-aspartate receptor antagonists. Several of these medications will also be evaluated in another project as adjunct medications for the treatment of withdrawal during detoxification from heroin. Together, data from these projects should shed light on the effects of these medications on a broad range of heroin's effects, from actual heroin taking to detoxification from heroin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LABORATORY STUDIES OF L-DOPA AND PSYCHOMOTOR STIMULANTS Principal Investigator & Institution: Silverman, Peter B.; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001 Summary: This proposal is a component of a center grant application to investigate "agonist" drugs as pharmacological adjuncts for the treatment of psychomotor stimulant dependence. Cocaine abuse and dependence represents a substantial continuing societal problem and methamphetamine abuse and dependence constitutes a substantial emerging problem. To date there is no pharmacological treatment of generally recognized of generally recognized efficacy for treatment of psychomotor stimulant dependence. The concept of substitution for these compounds with a safer stimulant, analogous to methadone and nicotine replacement therapies, is one that bears further investigation. A treatment which has a sound theoretical rationale, high likelihood of safety and reasonable probability of efficacy is l-dopa. Components of this Center Grant will investigate various aspects of l-dopa therapy. The specific objectives of this component are to evaluate l-dopa (administered with carbidopa) as to safety and possible efficacy in the University Clinical Research Center (UCRC). Four studies are
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proposed, the first three of which are in the nature of Phase I, II and III clinical trials, the fourth of which is a study of drug interaction. In the first study, acute dose ranging/tolerance and repeated dosing/tolerance experiments are to be conducted in normal healthy controls. In the second, stimulant abusers (cocaine dependent and methamphetamine dependent subjects) who are not seeking treatment will participate in a determination of safety and subjective effects of l-dopa. In the third study, treatment seeking stimulant-dependent individuals will be administered their first dose of carbidopa/l-dopa in the laboratory setting and adverse and subjective effects will be assessed. In the fourth study, the interaction of carbidopa/l- dopa with intranasally administered cocaine will be evaluated as will be the interaction of carbidopa/l-dopa with orally administered methamphetamine in stimulant abusers not seeking treatment. These experiments along with the associated clinical studies will provide use with the empirical evidence requisite to forming a sound opinion regarding efficacy of l-dopa in the treatment of psychomotor stimulant dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LONG ACTING OPIOID METABOLISM, DISPOSITION, DRUG INTERACTION, AND EFFECTS Principal Investigator & Institution: Kreek, Mary J.; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2001 Summary: The objectives of this subproject are (1) to study the distribution, metabolism, excretion, persistence, and drug interactions of long-acting exogenous opioids (narcotics) using methadone and LAAM as prototypic agents in methadone maintained patients; (2) to extend studies of the physiological effects of methadone and LAAM, as well as the effects of other pharmacotherapeutic agents in chemical dependency, and drug free treatment in chronic maintenance patients during treatment and following detoxification from methadone;; and (3) to determine the natural history of diseases common in addicts during treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNDROMES
MEDICATIONS
COMPARISON
OF
OPIOID
ABSTINENCE
Principal Investigator & Institution: Johnson, Rolley E.; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: New medications for treatment of opioid dependence have been recently approved (LAAM) or are currently under consideration for approval (buprenorphine) by FDA. Both are long-acting; buprenorphine may be unique in having a high safety profile, and limited physical dependence. Both may be useful in detoxification treatment. However, there is currently insufficient information concerning the syndrome associated with withdrawal from LAAM and buprenorphine and no systematic, well-designed, well-controlled studies comparing LAAM, buprenorphine and methadone detoxification have been conducted. Two complementary studies are proposed: 1) a residual laboratory comparison of withdrawal syndromes following abrupt discontinuation of LAAM, buprenorphine and methadone and 2) an outpatient comparison study of LAAM, buprenorphine and methadone in detoxification treatment. The first study will utilize the controlled environment of the residual research unit to obtain a detailed assessment of time course, intensity and symptom profiles
Studies 71
during spontaneous withdrawal from methadone, LAAM and buprenorphine. Two methadone doses (30, 100 mg/day) will be included to provide relevant benchmark comparison data. The second study will assess the comparative efficacy of the three medications in outpatient detoxifications during short (10 day) and longer-term (50 day) dose tapering schedules similar to those used in non- research treatment services. A methadone maintenance conditions will provide relevant comparison data for interpreting observed withdrawal symptomatology. Both studies will utilize rigorous and proven clinical trials methodology to obtain scientifically useful data directly comparing the characteristic opioid withdrawal syndromes associated with LAAM, buprenorphine and methadone.. Further, with the approval of LAAM and buprenorphine as treatment medications for opioid dependence, these studies will provide the information needed by clinicians for medications and dose selection in detoxification treatment as well as optimal dose reduction schedules for LAAM and buprenorphine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORING IN DRUG ABUSE NEUROIMAGING Principal Investigator & Institution: Renshaw, Perry F. Director; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: This is an application for a Midcareer Investigator Award in PatientOriented Research (K24) grant. The applicant is a psychiatrist/biophysicist who directs the McLean Hospital Brain Imaging Center (BIC). The BIC is an extremely active and productive research center with a major research interest in the development and rapid application of promising new magnetic resonance techniques for better understanding the acute and chronic effects of drugs of abuse on the brain. During the last 12 months, a total of 650 NIDA-funded research scans were completed by BIC investigators. The PI has been a NIDA-funded investigator since 1994 and he currently provides mentoring for 13 talented scientists, five of whom have NIH-funded Mentored Career Development Awards. This application is a request for five years of funding to relieve the candidate of a significant amount of administrative responsibility so that he can devote a greater effort to conducting research, growing professionally, and fostering the careers of the next generation of clinician scientists in the unique field of brain imaging and drug abuse. Funding of this K24 proposal, which will support 50% of the candidate's effort, would allow the PI to focus his research on a select group of the candidate's funded drug abuse research projects, to spend more time working with young investigators, and to obtain additional training in the areas of biomedical engineering, computing, and statistics. McLean Hospital has committed to hiring an administrator for the BIC to reduce the candidate's administrative responsibilities and to hire two additional faculty members to take over the candidate's responsibilities for research studies which do not involve drug abuse. In addition to the mentoring and training activities supported by the K24 award, the PI proposes to devote the remaining 50% of his effort to NBA-funded research grants on which he is PI: Magnetic Resonance, EEG, and Behavior After Cocaine (DA09448); High Field MR Research in Drug Abuse: A Bioengineering Partnership (DA14178); and on which he is Col: MR Spectroscopic Imaging During Methadone Maintenance (DA11321); and Medication Development for Cocaine Abuse: CDP-choline (DA11098). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
72 Methadone
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Project Title: METHADONE AND BUPERNORPHINE: ANTE- AND POSTPARTUM Principal Investigator & Institution: Jones, Hendree E. Assistant Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: Approximately 1/3 of opioid addicts are women of child-bearing age. Pregnancy during opioid dependence presents a complex array of therapeutic challenges. Methadone is the only maintenance pharmacotherapy recommended for use in pregnant opioid-dependent women. Methadone offers many benefits relative to continued untreated heroin addiction or medical detoxification, but it also has medical complications. Compared to non-drug exposed infants, opioid exposed infants have longer and more costly neonatal hospitalizations and display neurophysical and behavioral disruption. It is estimated that 55 percent-94 percent of infants exposed to opioids in utero will show signs of opioid withdrawal. Buprenorphine offers the potential of providing benefits comparable to methadone with fewer medical problems. Buprenorphine is reported to produce only a mild abstinence syndrome following abrupt withdrawal. Its potential will be assessed in a randomized controlled clinical trial comparing methadone and buprenorphine in this special population. Results will be compared to opiate dependent controls who choose nonpharmacological treatment. This comprehensive interdisciplinary effort will be conducted in the Center for Addiction of Pregnancy. Subjects randomized to equivalent optimal doses of methadone (N=35) or buprenorphine (N=35) will be followed through pregnancy and compared to nonpharmacologically treated (N=35) subjects. Primary outcome measures are: neonatal abstinence symptoms and length (days) of hospital stay. Secondary fetal/neonatal outcome measures are: standard antenatal measures, NICU Network Neurobehavioral Scale, fetal growth ratio, total anti-withdrawal medication given, infant cry behavior and physical birth parameters. Secondary maternal outcome measures include: treatment retention, objective and subjective measures o drug use, global assessments, dose adequacy and safety data. Additionally, mother and infant pharmacokinetic data will be collected to aid in interpretation of outcomes. The study will provide critical clinical data comparing the neonatal abstinence syndrome and safety/efficacy of methadone and buprenorphine in the mother and infant pre- and postpartum using rigorous scientific methodology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: METHADONE AND HIV DRUG INTERACTIONS Principal Investigator & Institution: Kharasch, Evan D. Professor; Anesthesiology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 17-JUL-2001; Project End 30-JUN-2006 Summary: The overall goal of this research is to improve methadone maintenance treatment, the cornerstone of opiate abuse therapy and a vitally effective strategy for HIV/AIDS risk reduction. Methadone disposition is characterized by extreme, unexplained and unpredictable inter- and intra- individual variability, causing opiate withdrawal, side effects, and treatment failures. Methadone intestinal first-pass metabolism and systemic clearance are catalyzed predominantly by cytochrome P4503A4. CYP3A4 variability and most importantly, CYP3A4 drug interactions, profoundly affect methadone first-pass metabolism and systemic clearance. Methadone is a newly recognized substrate for intestinal and CNS P-glycoprotein (P-gp), which determines methadone absorption and CNS pharmacodynamics in animals (a human
Studies 73
role is unknown). The HIV/AIDS protease inhibitors (HIV-PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) are exquisitely potent CYP3A4 modulators, causing significant and complex (short- vs long-duration effects) yet poorly understood drug interactions. HIV-PI are P-gp modulators in vitro, yet their clinical effects are unknown. Unfortunate anecdote, the current way of detecting methadone drug interactions, has recently identified clinically significant HIV-PI and NNRTI-methadone interactions, with adverse outcomes. Nevertheless, such interactions are poorly understood. The overall research objective is to identify the mechanism(s) of HIV-PI and NNRTI-methadone interactions, and more generally validate a novel in vivo CYP3A4 probe for drug interactions involving HIV-PI, NNRTI, and methadone, and generalizable to other HIV/AIDS drugs, drug abuse therapies, and CYP3A4 drugs. The specific aims are to: 1) validate the pharmacodynamics of alfentanil (a highly specific in vivo CYP3A4 probe) as a rapid, noninvasive, inexpensive pharmacokinetic surrogate and probe for hepatic and intestinal CYP3A activity and drug interactions;2) determine the role of P-gp in methadone intestinal absorption and CNS pharmacodynamics in humans;3) determine HIV-PI (ritonavir, indinavir, saquinavir, nelfinavir)and NNRTI (nevirapine, efavirenz) effects on intestinal P-gp activity, first-pass CYP3A metabolism, and hepatic CYP3A activity;4) identify mechanisms of HIV-PI and NNRTI alterations in methadone disposition and clinical effect, potentially caused by modulation of P-gpmediated intestinal absorption, CYP3A4-catalyzed first-pass metabolism, CYP3Adependent systemic clearance, and/or P-gp- mediated CNS accessibility;5) establish the ability of noninvasive in vivo probe of CYP3A activity to predict methadone disposition, and to rapidly and noninvasively detect and predict drug interactions with HIV-PI, NNRTI, and methadone.. Successful completion will provide fundamental new information on methadone disposition, improve the treatments and outcomes of opiate addiction and HIV/AIDS, and provide a novel technology for assessing CYP3A, the most important drug metabolism enzyme in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METHADONE DEVELOPMENT
ANONYMOUS--BEHAVIORAL
THERAPY
Principal Investigator & Institution: Galanter, Marc; Professor; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, NY 10962 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: This therapy development study systematically introduces Methadone Anonymous (MA), a 12-step program, into conventional methadone maintenance treatment (MMT) in order to improve the outcome of rehabilitation. A number of problems are apparent in the care of MMT patients: high illicit drug use, lack of motivation for successful community integration, and HIV-risk behavior. These have shown relatively little improvement from the impact of program enhancements like traditional social services and pharmacologic adjuncts. Although the 12-Step model typically involves rejection of dependency-producing agents in treatment, our findings to date suggest that it can enhance the rehabilitation of methadone patients when it embodies the acceptance of methadone maintenance. This benefit can be understood on theoretical grounds on the basis of MA's peer support, voluntary affiliation, and spiritual orientation. However, the feasibility of this MA format has yet to be empirically demonstrated. This project is therefore framed as an R21 grant because it involves the introduction of an approach based on a theoretical model of treatment drawn from another field, namely, the AA maintenance-free approach. The study will proceed as a randomized group design, to include an MA Facilitation (MAF) treatment group (N =
74 Methadone
96) and a comparison treatment-as-usual group (N = 96). The specific aims of this study are to: (1) prepare and evaluate an MAF manual for use by staff in the MAF condition; (2) assess the impact of MAF on outcome variables assessed at 6 months (e.g., illicit drug use, HIV risk behaviors); and (3) determine the impact of select patient characteristics (e.g., level of psychiatric distress, motivation) on change in MA attendance and illicit drug use among patients in the MAF condition. Consecutive admissions to the program will be randomly assigned to one of two treatment sites (standard methadone AT with MAF vs. standard MMT only). The development of the MA manual and results of this evaluation will provide pilot data for preparation of an RO1 proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METHADONE IN COMBO WITH AMPRENAVIR IN OPIATE ABUSERS Principal Investigator & Institution: Hendrix, Graig W.; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: This study is a prospective, open-label, pharmacokinetic interaction study of the effect of amprenavir on methadone in patients not infected with HIV, but on steady doses of methadone in methadone maintenance programs. Subjects will have a baseline assessment of steady-state 24-hour methadone pharmacokinetics, followed by initiation of amprenavir dosing, 1200 mg q12h. Subjects will have a 24-hour pharmacokinetic assessments ten days later, after sufficient time passes for a new steady state to be established (five half-lives). Subjects will serve as their own controls in a paired analysis of methadone kinetics. Amprenavir kinetics will be compared to subjects from other amprenavir only kinetic studies. Pharmacodynamic assessment (pupil diameter, cognitive function, symptom self report) are measured twice daily during the study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: METHADONE MAINTENANCE FOR PRISONERS Principal Investigator & Institution: Kinlock, Timothy W.; Friends Research Institute, Inc. Box 10676, 505 Baltimore Ave Baltimore, MD 21285 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 30-APR-2008 Summary: (provided by applicant): Most prisoners with histories of pre-incarceration heroin addiction do not receive treatment while incarcerated and seldom enter treatment upon release. Effective treatment for such prisoners is urgently needed because rapid readdiction typically follows release, placing these individuals at risk of HIV infection and other negative consequences of addiction. Additional research to develop effective treatments that begin during incarceration and continue in the community is clearly needed. Based on evidence of methadone maintenance treatment effectiveness in community settings, it appears an especially promising approach for inmates with heroin addiction histories. A five-year study is proposed to examine the benefits of a methadone maintenance treatment program for prison inmates who have been incarcerated for some time and are not currently addicted, initiating maintenance treatment prior to release from prison and continuing treatment in the community. Other than three studies of methadone maintenance with short-term jail inmates, the only study of longer-term inmates was a locally-conducted pilot study involving prison inmates in pre-release status. Based on this pilot research, which found that initiating maintenance treatment in prison is feasible and facilitates entry into community-based treatment after release, we are proposing a more rigorous examination of this unique
Studies 75
treatment approach. In the proposed study, prisoners with pre-incarceration histories of heroin addiction having 3-6 months left to serve before release (N=360) will be randomly assigned to one of three conditions: (1) initiation of methadone maintenance in prison, with transfer to community-based methadone maintenance with the same provider immediately upon release; (2) immediate access to methadone maintenance treatment upon release from prison, but no maintenance treatment in prison; and (3) no experimental intervention. This study design will permit disentanglement of the effects of two distinct program components, namely (a) the provision of methadone maintenance treatment prior to release, and (b) the availability of immediate entry into maintenance treatment in the community upon release. Participants in all three conditions will receive drug abuse counseling in prison, along with information on how to access treatment resources in the community. Participants will be assessed at baseline (study entry) and at 1, 3, 6, and 12 months following their release from prison. Outcome measures include: treatment entry and retention in the community; heroin use; cocaine use; HlV-risk behaviors; criminal activity; and employment. The proposed research will also examine the relationship of initial motivation for treatment, early criminal involvement, and cocaine abuse history to treatment outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METHADONE, BUPRENORPHINE AND FETAL DEVELOPMENT Principal Investigator & Institution: Jansson, Lauren M. None; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Lauren M. Jansson, M.D. is currently the Director of Pediatrics at the Center for Addiction and Pregnancy (CAP) at Johns Hopkins in Baltimore, Md. CAP is an urban, multidisciplinary treatment program for pregnant opiate and/or cocaine dependent women and their families. A clinical Scientist Development Award is sought to further the applicant's understanding of substance exposed fetal neurobehavior with attendant clinical application to the newborn. In addition, clinical issues germaine to methadone maintenance and lactation will be studied. Specifically, the current proposal will allow Dr. Jansson to obtain general training in fetal neurobehavioral development at JHU School of Population and Family Health Science. She will also gain certification in NICU Network Neurobehavioral Scale (NNNS) administration through colleagues in Providence, R.I. Basic research training in study design, methodology development, data base management, and data analysis will be provided through mentorship from several faculty at JHU School of Medicine in the Departments of Psychiatry and Medicine. In addition, coursework in Maternal and Child Health as well as clinical trial and laboratory-based research will be completed, as will grant writing courses and seminars. Throughout the 5-year funding period, acquired skills and knowledge will be applied through the development and conduct of several small-scale research studies. Specifically, four studies are proposed to examine: (1) Fetal neurobehavior in methadone maintained pregnancies at peak versus trough plasma levels, (2) Fetal neurobehavior in high dose (greater than 60 mg) versus low dose (less than 40 mg) methadone maintained pregnancies. (3) Fetal neurobehavior in methadone versus buprenorphine maintained pregnancies, (4) Methadone maintenance and breastfeeding. Across studies 1-3, substance exposed fetal neurobehavioral status will be compared to infant neurobehavioral status post-delivery. Clinical correlates will be elucidated in an effort to better understand and improve medical care for opiate-exposed newborns. In particular, Dr. Jansson hopes to elucidate variables that identify infants at greatest risk for neurobehavioral problems. Upon completing the 5-year funding period, Dr. Jansson
76 Methadone
plans to have written an RO1 grant application to pursue research ideas identified during KO8 funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MMT EFFECTS ON RCMRGLC IN OPIATE DEPENDENT PATIENTS Principal Investigator & Institution: Galynker, Igor;; Beth Israel Medical Ctr (New York) 1St Ave at 16Th St New York, NY 10003 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: Methadone maintenance therapy (MMT), a standard treatment for opiatedependent patients purportedly produces beneficial effects through its action as a substitute in an endogenous opioid deficiency syndrome. Nonetheless, direct evidence of persistant abnormalities in brain function of opiate-dependent patients, who are free of medication and illicit drugs of abuse, is lacking. The purpose of this study is to address this question by using the [F-18] fluorodeoxy glucose (FDG) method and positron emission tomography (PET) to assay regional cerebral metabolic rate(s) for glucose (rCMRglc), and index of local brain function. Subjects who have histories of opiate dependence will be compared with nonopiate-abusing control subjects matched for socioeconomic status, gender, and age. The proposed research will ask the following questions: 1) Is opiate dependence associated with persistent abnormalities in regional brain function, as assessed by measurement (as evidenced by differences in) of rCMRglc; and 2) Are potential abnormalities in rCMRglc, seen in abstinent patients at least six months after cessation of MMT as compared with controls, absent in patients who have received MMT for at least 6 months? Answers to these questions would have bearing on the theory that long-term deficiency of endogenous opioids leads to persistent cerebral dysfunction that can be ameliorated by MMT. The long-term goals of this project and its possible extensions are a comprehensive understanding of the relationship between neuroanatomical, neurochemical and clinical factors pertaining to opiate addiction, and its treatment, and the design of more effective therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODEL MEDICATIONS
FOR
SCREENING
HEROIN
DETOXIFICATION
Principal Investigator & Institution: Collins, Eric;; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001 Summary: Heroin dependence has reemerged as a significant public health problem in the 1990's. Detoxification is and will continue to be a common first step in the treatment of individuals with heroin dependence, but the two detoxification approaches in widespread use today, the methadone taper and clonidine-assisted detoxification, are flawed. There is a need for new pharmacological approaches to heroin detoxification. The research proposed here aims to develop and implement a model screening procedure to evaluate potentially promising new medications for use in heroin detoxification. Our approach is to carry out a series of three 7-day, three- arm randomized, double-blind clinical trials, each one comparing two matched promising medications for opioid detoxification with a clonidine- assisted detoxification. We incorporate a comprehensive assessment of withdrawal Severity, cognitive and motor performance, and follow-up data four weeks following entry into the study. Our first study compares two medications, a potentially less hypotensive alpha-2 agonist,
Studies 77
lofexidine, and a calcium channel antagonist, isradipine, directly with clonidine-assisted detoxification. Our second trial examines the potential utility of NMDA antagonists by comparing two noncompetitive NMDA antagonists, memantine and dextromethorphan, with clonidine. The third trial investigates the role of partial mu opioid agonists with differential kappa activities by comparing buprenorphine and butorphanol with clonidine. The strength of our approach lies in the controlled evaluation of potentially promising detoxification medications under consistent conditions. We expect to provide information about new mechanisms for medications development for opioid detoxification. We focus on the role heroin detoxification procedures may have in maximizing the likelihood of opioid abstinence and treatment retention following detoxification. While we recognize that detoxification is only the first step in treatment, we also believe that improving this procedure could increase the number of heroindependent individuals entering it, completing it, and continuing after it with more definitive treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOTHERING & ADDICTION:INTERNAL CONCEPTIONS OF PARENTING Principal Investigator & Institution: Suchman, Nancy E. Psychiatry; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2002; Project Start 10-JUL-2002; Project End 30-JUN-2007 Summary: (Provided by Applicant) During the past two decades, although much has been learned about risk factors associated with maternal addiction and parenting, little research has focused on the internal conceptions of drug-addicted mothers in the parenting role, and how these conceptions function as mediators in the parenting process. The goal of this mentored patient-oriented research career award is to allow the candidate to develop a research career in the area of maternal addiction and parental development. Dr. Suchman is currently the Project Director for the NIDA funded grant, "Relational Parenting Therapy for Opiate-Addicted Mothers" (R0l-DA11498) and has been examining the role of psychosocial risk in the parenting problems of opiateaddicted mothers. In the next several years, Dr. Suchman plans to conduct longitudinal research examining the role of internal conceptions of parenting in the parenting processes of cocaine and opiate-addicted mothers and its implications for parenting intervention development. Specifically, her research plan includes a 4-year longitudinal study of cocaine-addicted mothers and infants to ascertain mothers? internal representations of parenting and associations between internal representations and other parenting dimensions (e.g., psychosocial risk, parenting behaviors, child development). She will also examine cross-sectional data from opiate-addicted mothers of older children to ascertain associations between internal representations and parenting dimensions. Her proposed research will enable her to develop skills in the following areas: 1) qualitative assessment of internal working models of parenting, 2) assessment of parent-child interactions, 3) infant and child assessment, 4) longitudinal research design and data analytic strategies, 5) psychotherapy research, and 6) applications of developmental psychopathology to parental development. Dr. Suchman?s training combines formal course work with clinical research experience at several sites affiliated with the Yale School of Medicine and the Yale Child Study Center. She will work closely with Drs. Bruce Rounsaville, Linda Mayes, and Suniya Luthar to receive training in the above areas. In this way, Dr. Suchman will be well prepared to achieve her long-term career goal of conducting longitudinal research on the etiology of
78 Methadone
maladaptive parenting among drug-addicted mothers and applying her findings to the development of parenting interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MR MAINTENANCE
SPECTROSCOPIC
IMAGING
DURING
METHADONE
Principal Investigator & Institution: Pollack, Mark H. Director; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: (Applicant's Abstract) A resurgence in opiate abuse and dependence is occurring in several major U.S. cities, including Boston. Unfortunately, few studies have addressed the consequences of opiate abuse and dependence on cerebral metabolism or perfusion in human subjects. Additionally, no study to date has examined the neurochemical effects of the most widely utilized intervention for opiate abuse, methadone administration. Methadone maintenance (MM) has demonstrated efficacy in improving overall health and psychiatric symptoms in opiate abusers, improving their ability to function in society and reducing the economic costs of opiate addiction. Moreover, NIDA has recently recommended expanded use of MM for treatment of opiate addition (NIDA Notes, Nov./Dec. 1997). This proposal responds to RFA DA 98004 entitled "Neurobiological Effects of Drug Addiction Therapies." The purpose of this 5-year study is to examine the effects of methadone maintenance treatment on cerebral function in opiate dependent drug abusers, utilizing phosphorus magnetic resonance spectroscopic imaging (31P MRSI). Patients will undergo 31P MRSI at entry into a methadone maintenance treatment program, and have repeat scans after 6, 12 and 24 months of treatment. The relationship between response to treatment and cerebral function at initiation and during maintenance will be examined. Cerebral metabolic changes during methadone treatment will be compared to intensity and patterns of baseline and continued drug use, baseline and treatment-altered neurocognitive function, gender, ethnicity and psychiatric status. On the basis of cross sectional pilot studies, we hypothesize that opiate-dependent polydrug abusers will have baseline 31P MRSI abnormalities indicative of neuronal/glial membrane and bioenergetic dysfunction in both whole brain and in frontal, circulate and temporal cortices, as well as functional deficits in learning, recall, and attention. Additionally, we hypothesize that 31P MRSI abnormalities will improve in patients retained over a 2-year period of MM, and that the degree of 31P MRSI improvement will correlate with the degree of neurocognitive and Addiction Severity Index score improvement. This study will provide important new information on the nature of changes in brain chemistry associated with positive outcome (long term MM retention with minimal illicit drug use), intermediate outcome (MM retention with continued drug use) and negative outcome (early attrition from MM treatment). This information may be directly relevant to the design of more effective therapies for opiate dependence which will provide better symptomatic relief, resulting in reduced drug abuse and increased patient functionality in the high proportion of opiate dependent patients who do not experience optimal MM treatment outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAINSTEM
MU
OPIOID
RECEPTOR
REGULATION
IN
NEONATAL
Principal Investigator & Institution: Olsen, George D. Professor; Physiology and Pharmacology; Oregon Health & Science University Portland, OR 972393098
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Timing: Fiscal Year 2003; Project Start 15-DEC-1993; Project End 31-MAR-2007 Summary: (provided by applicant): The long-term goal of the proposed research is to understand mechanisms by which chronic in utero morphine and methadone exposure affect regulation and function of mu opioid receptors (MOR) in respiratory control areas of newborn brainstem. Respiratory depression is induced by endogenous opioid peptides and exogenous opioids that activate MOR. A critical brainstem site for these effects is the nucleus tractus solitarius (NTS), which integrates sensory signals and drives respiratory muscles. Profound disturbance of neonatal breathing is a welldocumented consequence of maternal opioid abuse. These neonates exhibit withdrawal hyperventilation and an increased incidence of sudden infant death syndrome (SIDS). The proposed studies are essential for understanding normal respiratory development, drug-induced changes, and effective treatment of pregnant heroin addicts and methadone maintained patients. The exact role of NTS MOR in neonatal congenital narcotic dependence and these respiratory disturbances is unknown. For anatomical, physiological, and pharmacological reasons, the guinea pig is a superb model for study of maternal opioid abuse. Guinea pig kappa opioid receptor has been cloned, but only partial sequences of MOR and delta opioid receptors have been available. However, our laboratory has recently determined the complete guinea pig MOR cDNA sequence. Availability of this sequence will enable us to define for the first time guinea pig MOR pharmacology, and systematically compare it to human and mouse MOR. Research is guided by four hypotheses: 1) guinea pig MOR is functionally similar to human MOR with respect to mu agonist efficacy, binding kinetics, and activation of G-protein, but different from murine MOR; 2) methadone induces respiratory depression and is equipotent to, but of longer duration than morphine in the neonatal guinea pig; 3) chronic in utero morphine and methadone exposure results in increased functional MOR on the cell surface, but decreases the coupling efficiency of MOR with G-proteins in the NTS; 4) chronic in utero morphine and methadone exposure up-regulates MOR mRNA in the NTS. Hypotheses are explored through four specific aims: 1) to compare mu agonist selectivity and potency, and development of cellular tolerance for guinea pig, human and murine MOR each expressed in stably transfected CHO cells; 2) to prove that the respiratory effects of methadone are similar to morphine in the neonatal guinea pig; 3) to study the effects of morphine and methadone on guinea pig MOR in NTS of brainstem sections from guinea pig neonates exposed in utero; and 4) to quantitate MOR mRNA in NTS from guinea pig neonates exposed to morphine and methadone in utero. These studies will provide developmental information on guinea pig NTS MOR following chronic in utero opioid exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NARCOTIC DRUG AND OPIOID PEPTIDE BASIC RESEARCH PROJECT Principal Investigator & Institution: Woods, James H. Professor; Pharmacology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 15-JUL-1997; Project End 30-JUN-2007 Summary: (provided by applicant): The Narcotic Drug and Opioid Peptide Basic Research Project enters its 31st year with continued vigor and enthusiasm. Several aspects of the Center are logical extensions of efforts of earlier years; other aspects represent entirely new areas of interest. Included in the former category are studies that refine and analyze the pharmacological effects of opioids in the rhesus monkey. Our research on the analgesic, respiratory, and reinforcing effects of opioids will continue
80 Methadone
into new avenues. In addition, studies using newly developed analgesia are included that may provide evidence for novel, additional pathways through which opioids can provide therapeutic action against pain and inflammatory processes. Similarly, studies of the reinforcing effects of opioids will be extended to new procedures that may provide evidence of increasing reinforcing effects of opioids during withdrawal and eventually, protracted withdrawal. The drug discovery program will continue to evaluate the in vivo and in vitro effects of opioids in rodents and in vivo effects of opioids in nonhuman primates. One objective of this aspect of the Center is to determine the mechanism by which buprenorphine exerts its novel actions that make it an extremely interesting pharmacotherapy for opioid abuse. The work of the human behavioral pharmacology laboratory continues on the focus of the evaluation of buprenorphine as a pharmacotherapy and makes direct comparison to methadone in some its pharmacology. Studies utilizing labeled carfentanil in PET imaging studies will compare buprenorphine's binding to central mu-receptors with its antagonism of hydromorphone's pharmacological effects. A new area of research is a major chemical venture toward the development of radiolabeled PET ligands specific to opioid function in pharmacologicical, physiological, and pathophysiological Conditions in primates and humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBEHAVIORAL CONSEQUENCES OF PRENATAL OPIATE EXPOSURE Principal Investigator & Institution: Smart, Rebecca S. Psychology; Hunter College 695 Park Ave New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-JUN-2001 Summary: Abuse of substances such as heroin and methadone during pregnancy is widespread and there is concern about the placental transfer of such drugs and the possible effects on the developing fetus. There has been much basic research on the effects of prenatal opiate exposure on both behavior as well as neural function. However, much of this research has focused on the early neonatal period or adulthood. The effects on the juvenile animal have not been as well investigated. It is possible that prenatal opiate exposure may have subtle neural and behavioral consequences that are not apparent in the neonatal period or that emerge later. One system that is most likely affected by prenatal exposure to opiates are the endogenous opioids, which develop prenatally. Opioids mediate many behaviors in both the human and the rat. One such behavior is play, a social behavior that is exhibited by juveniles of most mammalian species. Acute administration (in the juvenile period) of opiate agonists increase play, whereas acute administration of opiate antagonists decrease play. When exposure to opiates occur prenatally, differences in play are also observed, depending on the method of prenatal administration. Intermittent administration of an opiate agonist (i.e. morphine) prenatally increases play, but continuous prenatal administration decreases play. Intermittent prenatal administration produces fluctuating (blood plasma) opiate levels, causing the dam and the fetuses to experience both the effects of the opiate and short term withdrawal from the opiate. Conversely, chronic administration produces relatively constant opiate levels. Thus, different methods of prenatal administration could have different neural consequences, which would subsequently produce the changes in play behavior. The specific aims of this proposal are to examine the effects of different methods of prenatal opiate administration over the time course of gestation on play behavior and the endogenous opioids. These aims will be accomplished through both behavioral and molecular techniques. Understanding the neural mechanisms
Studies 81
underlying the behavioral changes will provide a model from which to examine the consequences of maternal drug use in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBEHAVIORAL DEVELOPMENT
STUDIES
OF
OPIATE
DRUGS
IN
Principal Investigator & Institution: Barr, Gordon A. Professor of Psychology; Psychology; Hunter College 695 Park Ave New York, NY 10021 Timing: Fiscal Year 2001; Project Start 10-APR-1997; Project End 31-MAR-2002 Summary: (Applicant's Abstract) Human infants are often exposed to opiate drugs because of illicit opiate use by the mother, or because of therapeutic use of methadone.. The consequences of this exposure are largely unknown. Furthermore, pain is a significant clinical problem for preterm infants or full term infants undergoing medical procedures, in part because it can result in an established pain syndrome. Thus adequate and continued alleviation of pain is an important factor in the survival of human infants after major medical interventions. Yet adequate and safe relief of pain in neonates is a difficult clinical problem because these drugs act differently in the infant, with a different set of side effect. Little is known of the mechanisms of action of opiate drugs in the immature organism, following either illegal or therapeutic use. This application is for an independent research scientist award to allow the principal investigator to expand his work on the mechanisms of action of opiate drugs, and the biological processes that opiates affect. Several lines of research, partly funded by NIDA and NINDS, examine these problems. First, we define the development of inflammation and alterations in pain perception associated with inflammation during early development in the rat. We examine the effects of opiates on the pain process when given locally to the site of inflammation or centrally, and describe alterations in opiate receptors and peptides in neural and immune tissue as a result of inflammation. Second we propose to study the defensive response of the young animal to a variety of threatening stimuli, including pain, and study the role of central opioid systems in those responses. Third, we describe the role of various brain sites mediating the behavioral and affective consequences of opiate withdrawal and examine the behavioral effects, including changes mother-infant interactions, of spontaneous opiate withdrawal in the neonate. Finally, we will integrate these three lines of work by studying whether or not pain perception, defensive and autonomic responses to pain and other threats are altered in the infant undergoing opiate withdrawal. These experiment will provide data on the role of acute and chronic opiates in normal functioning and the response to significant environmental threats in the immature animal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBIOLOGY MAINTENANCE
OF
COGNITIVE
GAINS
WITH
OPIATE
Principal Investigator & Institution: Forman, Steven D. Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 30-APR-2003 Summary: (Applicant's Abstract) We propose a longitudinal study to monitor prefrontal cortical functioning in 56 heroin-dependent patients during the course of opiate maintenance. Using a newly developed variant of the Go/No Go task and functional magnetic resonance imaging (fMRI), we will assess whether prefrontal cortical activity increases with clinical improvement, both in dorsolateral regions associated with delay-
82 Methadone
dependent processing and in ventral areas associated with inhibitory processing. We will additionally use a combined fMRI/microdialysis system in a rat model to measure the neurochemical changes in those relevant brain areas identified in the clinical investigation. Heroin dependence remains a major public health problem in the United States. Opiate maintenance is the most effective treatment modality with an estimated 115,000 individuals currently receiving methadone maintenance (IOM Report, 1995). Despite its demonstrable effectiveness and widespread use, very little is known about the cognitive effects of chronic methadone.. We know that opiate maintenance treatment allows opiate addicts to cease their relentless search for illicit opiates, accompanied by psychosocial stabilization in a number of domains including decreased criminal activity, increased productivity, increased employment and educational pursuits. Clinically, as the destabilized lifestyle of the addict is marked by impulsivity (by diagnostic definition), it appears apparent that clinical improvement must be accompanied by improvements in this cognitive characteristic. Opposition to opiate maintenance has always arisen from the view that opiate maintenance merely swaps one abused narcotic for another. From both a clinical and sociopolitical standpoint it is obviously relevant to establish that opiate maintenance treats a cognitive deficit induced by previous illicit opiate abuse. We have found no study addressing whether and how opiate maintenance affects impulsivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROCHEMICAL SUBSTRATES OF SLEEP HOMEOSTASIS Principal Investigator & Institution: Dorsey, Cynthia M.; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Difficulty initiating/maintaining sleep afflicts up to 30% of the population, yet the neurochemical processes associated with sleep and sleep disturbances have not been clearly identified. A better understanding of EEG slow-wave activity and its role in recovery from sleep loss could be invaluable in elucidating the homeostatic sleep mechanism and shedding light on how to treat disturbed sleep. Further, sleep disturbances contribute to relapse to drug use and such efforts might help address this serious public health problem. The purpose of the study is to identify neurochemical markers of sleep mechanism in an intact and an impaired system, by evaluating changes in brain chemistry produced by disrupted sleep. In response to RFAHL-01-009, "Interrelationship between sleep and heart, lung, and blood diseases" we propose two experiments. In the first, polysomnography (PSG) and phosphorous magnetic resonance spectroscopic imaging (31P MRSI) will be collected at baseline, after sleep deprivation, and after recovery sleep in controls and in methadone-maintained subjects. Measures will be repeated at 1 and 3 months to determine if the effects persist. In the second experiment, PSG and 31P MRSI data will be collected from unmedicated cocaine-dependent and opiate-dependent subjects during acute withdrawal and at 1 and 3 months post withdrawal. As the abstinence profile for sleep disturbance differs in these groups (hypersomnia vs insomnia, respectively) this experiment will help delineate the conditions under which altered brain bioenergenics exist. 31P MRSI can be used to measure global and focal changes in high energy phosphate alpha-,gamma,beta-NTP (ATP). Our pilot data showed significant increases in beta-NTP and decreases in phospholipid catabolite production after recovery following sleep deprivation in control subjects. 31P MRS changes have been observed in chronic opiate-dependent individuals at baseline, but have not been evaluated during sleep. Chronic sleep disturbances have been reported in opiate abusers and methadone-maintained patients
Studies 83
and the homeostatic sleep mechanisms may be impaired in chronic opiate abuse. We hypothesize that methadone-maintained subjects will have decreased beta-NTP and will exhibit smaller slow wave sleep rebound and a more modest or no increase in beta-NTP after recovery. Further, the neurochemical response to sleep deprivation in these subjects will approach that of controls over time b-NTP will increase during cocaine withdrawal and decrease during opiate withdrawal, reflecting their differential effects on sleep during this time. Collectively, these studies may identify neurochemical markers for the recovery function of sleep, thus enhancing our understanding pf basic sleep mechanisms and potentially leading to new and improved treatments for sleep disturbances in both the substance-abusing and general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW MEDICIATIONS FOR COCAINE, HEROIN AND POLYDRUG ABUSE Principal Investigator & Institution: Negus, S S.; Mc Lean Hospital (Belmont, Ma) Belmont, MA 02478 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006 Summary: Project II: New Medications for Cocaine, Heron and Polydrug Abuse is part of a new PO1 proposal entitled Cocaine and Polydrug Abuse: New Medication Strategies. The purpose of this project is to assess candidate medications for the treatment of polydrug abuse involving both cocaine and opiates. Abuse of cocaine and opiates continues to be a significant public health problem, and polydrug abuse involving combinations of cocaine and opiates. Abuse of cocaine and opiates continues to be a significant public health problem, and polydrug abuse involving combinations of cocaine and opiates (known as a 'speedball") is one prevalent form of multiple drug use. Although effective medications exist for the treatment of opiate abuse, there is no uniformly effective medications for the treatment of cocaine abuse, and polydrug abuse involving both cocaine and opiates is especially refractory to treatment. Our preliminary studies suggest that treatment of speedball abuse may be best accomplished with medication combinations that target both dopaminergic mechanisms underlying the effects of cocaine and opioid mechanisms underlying the effects of opiates. Accordingly, we propose to assess the effects of medication combinations as candidate treatments for speedball abuse. The compounds proposed for study are divided into two categories. To target the cocaine component of the speedball, we propose to study dopamine reuptake inhibitors (indratraline, RTI-113, GBR12909), dopamine D1 receptor agonists (SFKF82958, SKF77434) and a dopamine D1 receptor antagonist (SCH39166). To target the opiate component, we propose to study the high efficacy mu agonist methadone, the intermediate efficacy mu agonist buprenorphine and the opioid antagonist nalmefene. Dopaminergic and opioid compounds will be studied alone and in combination in monkeys trained to discriminate or to self-administer cocaine alone, heroin alone, or cocaine/heroin combinations. Drug self-administration will also be examined during withdrawal from chronic medication delivery. Treatment effects on drug- maintained responding under a progressive ratio schedule will also be examined. The reinforcing effects of the most effective and selective medications or medical combinations will be assessed using drug self- administration substitution studies. This comprehensive series of studies will advance our understanding of the neurobiology of speedball abuse and the relative effects of candidate treatment medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
84 Methadone
•
Project Title: NOVEL PHARMACOTHERAPIES FOR OPIOID WITHDRAWAL Principal Investigator & Institution: Walsh, Sharon L. Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 30-JUN-2002 Summary: The physical dependence and withdrawal syndrome produced by chronic opioid use represents a significant hurdle for those patients seeking treatment. Available pharmacological detoxification agents are circumscribed and the use of some are rigorously regulated. Recent advances in neurobiology suggest that central noradrenergic and glutamateric processes are intimately involves in the development of opioid physical dependence and withdrawal. These studies will evaluate the ability of four novel medications whose effects are exerted through these neurotransmitter systems for their ability to attenuate or block opioid withdrawal using controlled laboratory procedures. The targeted study drugs are 1) lofexidine, an alpha2-adrenergic receptor agonist, 2) memantine, a non competitive NMDA receptor antagonist, 3) lamotrigine, a NA+ channel blocker with indirect glutamate antagonist properties, and 4) acamprosate, a post-synaptic glutamate antagonist; each drug will be evaluated in a separate study. Participants will be healthy adult volunteers who are physically dependent on opioids (n=10/study). Participants will be stabilized as outpatients for a period of at least 4 weeks on methadone (30 mg p.o./day) prior to inpatient admission. These studies will employ a model of antagonist precipitated withdrawal; this method has been shown to replicable, generalizable to spontaneous withdrawal, and welltolerated by opioid-dependent patients. The effects of acute pretreatment with each test agent (placebo and 3 active doses) on the subjective and physiological response to intramuscular challenge with placebo or naloxone (0.` & 0.3 mg) will be evaluated during controlled experimental sessions. Using this design, the safety and pharmacodynamic profile of each novel drug will be characterized alone, and the efficacy of those agents to suppress withdrawal will be evaluated over a range of test doses and two different withdrawal intensities. These studies will provide new information about the safety and pharmacodynamic effects of these novel agents, may provide some insight into the neural mechanisms which underlie opioid physical dependence in humans, and, most importantly, will serve as a first step in the development of new pharmacotherapeutic strategies for the treatment of opioid withdrawal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: OFFICE BASED METHADONE PRESCRIBING II Principal Investigator & Institution: Drucker, Ernest;; Montefiore Medical Center (Bronx, Ny) Bronx, NY 104672490 Timing: Fiscal Year 2001; Project Start 05-SEP-1997; Project End 31-MAR-2005 Summary: (Applicant's Abstract) This is the continuation and expansion of a study (RO1 DA11324) examining the practicality, safety, and clinical efficacy of the office based prescription of methadone by primary care practitioners. The current study population consists of a cohort of 150 women drawn from our Methadone program and randomly assigned to office based prescribing (OBP) or usual care in Methadone Maintenance Treatment Programs (MMTP). At 12 months follow-up, we have found that OBP produces equivalent treatment retention and reductions in illicit drug use, compared to the controls in MMTP. Over 50% of our 12,000 current MMTP patients meet the eligibility criteria for OBP-at least 6 months in MMTP, a stable dose of methadone, and some "take home" privileges. As was found in prior observational studies outside the
Studies 85
U.S., it appears feasible to integrate methadone prescribing into office-based medical practice. In the continuation of this study, we propose to follow the current cohort of 150 women for an additional 24 months (for a total of 36 months), to "crossover" 50% of the female controls into OBP, and to add 100 male patients to the randomized design (50 OBP and 50 MMTP). By increasing the size and diversity of the cohort and following them for a total of 3 years, we will both increase the generalizability of our preliminary findings. We will initiate a health services component to study the integration of methadone prescribing within routine medical practice-evaluating patient and provider experiences and satisfaction, the patients' utilization and costs of primary and specialty medical care (with special attention to Hepatitis C, HIV/AIDS, and menopause). Secondary outcome measures (subsidiary or pilot studies) will continue to examine evidence of the use of other drugs (e.g., cocaine), and social adjustment (i.e. work home, criminal activity) In addition, as part of our exploration of alternative models of Methadone treatment, we propose to conduct a pilot study of community pharmacy dispensing of methadone for a sub- group of 20 stable patients (in both OBP and MMTP) who have been in the study for at least 12 month. Both the sponsoring medical institutions' methadone and medical care programs and the group of 15 primary care and specialist physicians currently prescribing Methadone and providing medical care for these patients have agreed to continue participating in the study and to expanding the number of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPIOID DEPENDENCE AND PATHOLOGICAL GAMBLING Principal Investigator & Institution: Blanco, Carlos; Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: The goal of this mentored clinical scientist award is to promote the developing research skills of Carlos Blanco, M.D., Ph.D. a board- certified psychiatrist, by focusing in on the evaluation and treatment of methadone-maintained patients with comorbid pathological gambling. As a resident and fellow, Dr. Blanco has studied the course of substance abuse disorders with comorbid psychiatric disorders, and conducted preliminary studies on the biological basis and pharmacological treatment of pathological gambling. Over the course of this award, Dr. Blanco plans to carry out a program of research including cross-sectional studies of clinical severity and neuropsychological functioning in opiate dependent patients with and without pathological gambling and controls, and a randomized clinical trial of fluvoxamine combined with manual- guided cognitive-behavioral relapse-prevention therapy (CBT/RP) in methadone maintained patients with pathological gambling. This proposed research will be complemented by a training plan, under the sponsorship and guidance of Dr. Edward Nunes, together with the faculty and resources available at Columbia University. Dr. Blanco's training plan combines formal course work with individual tutorials with a range of expert consultants. He will receive training in the following areas: design and methods of clinical studies; controlled medication trials; methods of behavioral therapy research; neuropsychology; biostatistics and epidemiology. Together with the planned research, this program will provide Dr. Blanco with a unique training that will prepare him to conduct independent clinical research in the field of addictions and to achieve his long-term research career goal of increasing our understanding and improving the treatment of patients with substance abuse with comorbid pathological gambling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
86 Methadone
•
Project Title: OPIOID DEPENDENCE: CANDIDATE GENES AND G X E EFFECTS Principal Investigator & Institution: Nelson, Elliot C. Assistant Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This R01 application seeks to conduct a case-control genetic association study of opioid dependence with inclusion of childhood trauma history as a risk modifying variable. Cases (N=1500) will be ascertained from the large methadone (and buprenorphine) maintenance treatment population of New South Wales, Australia. Controls (N=1500) will be ascertained via employment offices and medical clinics in proximity to areas where maintenance treatment is provided. The project s aims are as follows: AIM 1 To interview and collect blood samples from 1500 opioid dependent individuals and 1500 matched controls. AIM 2 To identify polymorphisms and/or mutations in candidate genes to be typed in cases and controls. AIM 3 To assess retrospectively history of childhood trauma to enable its inclusion as a risk modifying variable. AIM 4 To analyze genotype and interview data to test for candidate gene effects on opioid dependence, and their moderation by history of childhood trauma. The latter analyses will target genes whose products are known from Prior research to be involved in: (i) stress-sensitive mediation of the perceived positive effects of opioids; (ii) stress-induced opioid relapse; and (iii) opioid regulation of the stress response. The design seeks to improve upon prior work by: 1) undertaking the investigation in a sample of adequate size several-fold larger than the largest of prior association studies of opioid dependence) to provide substantial power; 2) using a welldefined, well-characterized phenotype (i.e. the DSM-IV diagnosis of opioid dependence nade via in person interview using the CIDI, an instrument with established reliability and validity); 3) applying conservative corrections for multiple testing; 4) employing genomic controls to control for population stratification; and 5) incorporating childhood abuse history as a risk modifying variable in analyses to determine whether evidence is found for significant G x E interactions. Candidate gene selection will be based on information gleaned from animal and human studies, focusing on reports of association with opioid dependence and related phenotypes as well as studies that have demonstrated persistent pathophysiologic changes in adult animals and humans with a history of early trauma. Single nucleotide polymorphisms (SNPs) of adequate frequency will be located by searching available databases with preference given to functional polymorphisms ant hose for whom prior studies have reported association. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: OPIOID FUNCTIONS OF MACROPHAGES AND MONOCYTES Principal Investigator & Institution: Renaud, Fernando L.; University of Puerto Rico Rio Piedras Rio Piedras Sta San Juan, PR 00931 Timing: Fiscal Year 2001 Summary: Description (Adapted from Application): The long-term goal of this project is to determine how opiates, including some commonly used in drug addiction therapy, affect macrophages, a key cell in immune defenses. This is important because it has been postulated that the susceptibility of drug addicts to infections may be due, at least in part, to suppressive effects of opiates on important components of the immune system Recent observations in this laboratory show that the effect of morphine on phagocytosis by macrophages is dependent on the concentration of the drug and conditions of exposure: acute exposures are inhibitory, whereas chronic exposure leads to a putative tolerant/dependent state. The investigators plan to extend their observations and study
Studies 87
the effect of morphine on respiratory burst activity (RB) and NO (nitric oxide) production. Effects on RB will be measured by flow cytometry, and NO production will be determined using the Griess reagent. They also plan to test the effect on these processes, including phagocytosis, of opiates used in drug addiction therapy, such as methadone, L-alpha-acetyl-methadol (LAAM) and buprenorphine. This will provide information about any possible deleterious effects that these drugs may have on the immune system of the addict. Finally, they plan to initiate studies on the effect of morphine, methadone, LAAM and bupremorphine on phagocytosis by human monocytes. Monocytes will be obtained from both control donors and HIV- methadone patients with known medical history. This will allow them to determine if the observations on murine macrophages are of relevance to understand the possible role of opiates in the immunosuppression observed in drug addicts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPIOID INDUCED ALTERATIONS OF IMMUNE STATUS Principal Investigator & Institution: Lysle, Donald T. Professor; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 30-APR-2002 Summary: These goals will be accomplished within the framework of three existing NIH funded projects. The first project, entitled Behavioral Determinants of Opioid/Immune Interactions, provides an examination of Opioid-induced alterations of immune status with emphasis on the role of the central nervous system and pharmacological variables in these interactions. Specifically, the proposal is to conduct studies on the effects of acute and chronic Opioid administration on immune function, and identify the specific brain regions involved in those effects. The second project entitled Immune Alterations Mediated by conditioning, examines how conditioning processes can modulate immune status. This proposal involves examining the role of endogenous opiates in conditioned modulation of immune function. The third project, entitled Opioid-induced alterations of nitric oxide production by peripheral macrophages. This project will determine the subtype(s) of Opioid receptors involved in Opioid-induced alterations of nitric oxide production, and characterize the effect of Opioid administration on nitric oxide production in vivo. Collectively, these projects will provide important new information about Opioid- induced modulation of the immune system, and this award will enhance these investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OPIOID WITHDRAWAL
MAINTENANCE:
OPTIMAL
STABILIZATION
&
Principal Investigator & Institution: Grabowski, John G. Professor; Psychiatry and Behavioral Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 30-JUN-2005 Summary: (provided by applicant) Opioid dependence is a recurring problem. Methadone and LAAM are effective therapeutic agents similar in many respects. Yet some features of dosing are not well defined. Two studies will be conducted examining dosing and dose reduction strategies in agonist (LAAM) treatment of opioid dependence. Results of the two linked, but distinct, studies of LAAM administration will be generalizable to methadone or buprenorphine. Study I will be a 5 month blind dosing study with three dose stabilization strategies and a Cognitive Behavior Therapy (CBT) base4ine. There will be three groups of 26 subjects each: 1) LAAM stabilization
88 Methadone
based on mg/kg weight/day+CBT (e.g., at 70 kg, dose will be 490 per week, distributed at 29 percent Monday, 29 percent Wednesday, and 42 percent Friday; 2) LAAM stabilization based on opioid negative urine screens and self reported symptoms+CBT; 3) LAAM stabilization at 50 mg per day equivalent+CBT (i.e., 350 per week distributed 29 percent, 29 percent, 42 percent). All subjects will be screened with the SCID, drug history, and medical evaluation based on our well-defined and rigorous techniques. A positive urine screen and clear evidence of current use, along with evidence of 5 years of use will be required. Cocaine and other drug use at intake and during treatment will be measured but will not be a condition for entry or exclusion. However, concurrent dependence (except nicotine) will be exclusionary. This study will elucidate dosing strategies. The study is based an our work with methadone, experience using a 1.1 mg/kg methadone dose, discussion with clinicians and researchers, and the methadone and LAAM literature. Study II will examine dose reduction strategies over a six-month period. Baseline therapy will be enhanced Clinical Management that recalls/reviews skills acquired in Study I. Only subjects enrolled in Study I and meeting the criteria for entry (low rate positive opioid screens and measured "Readiness to Change") will be accepted. Dose will be distributed as in Study I (29 percent/29 percent/42 percent). LAAM dose reduction will be at approximately 10 percent per week to 15-20 percent of initial dose and then discontinued. Two groups, 28 subjects each, will be 1) blind dose reduction and 2) open dose reduction. Screening/measurement will continue as in Study I. Blind group subjects will continue to receive placebo to study end. Retaining subjects even after reaching discontinuation will permit direct follow-up and there will be a one-month follow-up after the last visit. The work extends our initial preliminary examination of the blind-open procedure. In combination, the two studies will elucidate consequences of different dosing strategies and should enhance treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PAIN ANALGESIC RESPONSE IN OPIATE DEPENDENCE Principal Investigator & Institution: Ling, Walter; Professor; Friends Research Institute, Inc. Box 10676, 505 Baltimore Ave Baltimore, MD 21285 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 30-APR-2004 Summary: (Applicant's Abstract) There is an increasingly large population receiving opiates on a chronic basis, either for treatment of opiate dependence or for treatment of chronic pain. Managing pain in opiate maintained individuals is a challenging problem. The development of opioid tolerance and dependence may result in altered pain sensitivity and subsequent response to additional opioids. Many clinicians believe addicts cannot benefit from further opiate administration because they are tolerant to the analgesic effects. Others believe that if an addict is maintained on an opiate agonist, that medication provides adequate analgesia for acute pain. Patients are reluctant to give accurate histories because clinicians often withhold opioid analgesics from patients with a history of drug abuse. Those who do complain are viewed suspiciously and their complaints ignored. Currently there are few guidelines to assist clinicians and those that do exist are based on experience and consensus rather than evidence-based research. This study proposes to examine: 1) how patients on opiate maintenance (either buprenorphine or methadone) experience pain (tolerance and threshold) and how they are different from non-opiate dependent individuals, 2) how patients maintained on methadone and buprenorphine differ from normal controls in response to added opiate and non-opiate analgesics and 3) how therapeutic plasma concentration levels of morphine for analgesia differ in methadone and buprenorphine maintained patients compared to normal controls. The results of this proposed study will help develop
Studies 89
systematic guidelines for clinicians in the management of pain in opiate maintained individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT
PARENT-CHILD
INTERACTIONS
DURING
ADDICTION
Principal Investigator & Institution: Wilson, Jeffrey J. Psychiatry; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (Provided by Applicant) The goal of this K-23 award is to provide the applicant, a psychiatrist with advanced training in both child/adolescent and addiction psychiatry, with the advanced training needed to develop a paradigm to study and treat the transmission of addictive vulnerability (AV) among high-risk families. Preceptors and consultants for this award have been selected with the long-range intent of designing interventions to reduce AV through the treatment of parental addiction, child externalizing behavior (CXB), and the improved identification of communication problems within these families. Formal education in therapeutic interventions (including behavioral, psychoeducational and psychopharmacological approaches) and statistical methods complement this training. Among families with addicted parents, CXB may mediate the transmission of AV. Hence early identification and effective treatment of CXB may also reduce AV. Although parental substance abuse has multiple deleterious effects on children, little is known regarding the needs of these children and their families once their parents are treated for addiction. CXB is closely linked to coercive patterns of interaction between parents and their children, and these interactions may adversely effect both children and parents. A one-year prospective study of 100 families with a parent-proband in methadone maintenance treatment and their 6-9 year old children has been designed to better identify the treatment needs of these families. Parental substance use will be prospectively assessed as a predictor of child externalizing behavior, considering parent-child interactions as mediators or moderators of this relationship. The role of additional parent (e.g., comorbid psychopathology, gender, exposure, ethnicity, SES) and child (baseline externalizing behavior, comobid psychopathology, language ability) factors will also be considered in this developmental model of addictive vulnerability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARTNER-ORIENTED DRUG TREATMENT AND HIV RISK REDUCTION Principal Investigator & Institution: Iguchi, Martin Y. Director; Rand Corporation 1700 Main St Santa Monica, CA 90401 Timing: Fiscal Year 2001; Project Start 11-SEP-2001; Project End 31-JAN-2004 Summary: (provided by applicant): Methadone maintenance is an effective tool for reducing HIV risk and incidence among IDUs. All too often, however, individuals in methadone treatment continue to use opiates and other drugs, usually with a close friend or family member not currently enrolled in treatment. One response to this problem is to encourage at least one member of the methadone client's personal drugusing network to also enter treatment, thereby reducing the number of individuals presenting drug use opportunities. In this pilot study, 268 new methadone treatment entrants (Index Participants) will be interviewed and invited to bring in an opiate using sexual partner, family member, or close friend (Partner participants) described as
90 Methadone
belonging to their current personal injection drug-use network for interview. We anticipate that half of the 268 will be able to recruit a Partner for interview. The resulting 134 Partner participants will be randomly assigned to either the Intervention condition (offered 13 weeks of free methadone maintenance) or to a Control condition (no offer of free treatment). Self-report, urinalysis records in the clinical charts, and other biological indicator data (hair samples) will be collected at baseline and 4 months postrandomization to assess treatment outcomes, change in HIV risk behaviors, and change in personal drug-using network characteristics for both Index participants and their designated Partner participants. This two-group, random assignment pilot study is designed to address the following specific aims: Specific Aim 1: to determine if offering free drug treatment to one Partner will improve treatment outcomes and reduce HIV risk behaviors among Index participants. Specific Aim 2: to determine if offering free drug treatment to the Partner will result in reductions in Partner participant's HIV risk behaviors and drug use. Specific Aim 3: to determine if offering free drug treatment to one Partner will significantly alter the size, density, and stability of the personal drugusing network of the Partner, and ultimately of the referring Index. The proposed study addresses a practical public health problem, that ongoing drug use during methadone treatment tends to be initiated by close friends, family members, or significant others. The overall goal of the proposed study is to demonstrate that treatment outcomes can be improved and HIV risk behaviors reduced by involving at least two network members in drug treatment simultaneously. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHWAYS TO RECOVERY FOR SUBSTANCE ABUSERS IN TREATMENT Principal Investigator & Institution: Scott, Christy K.; Chestnut Health Systems 1003 Martin Luther King Dr Bloomington, IL 61701 Timing: Fiscal Year 2002; Project Start 20-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Substance use dependence with multiple cooccurring problems is increasingly recognized as a chronic, relapsing condition that may last for decades and require multiple episodes of care over many years before reaching a sustained state of remission. While most treatment research has focused on single episodes of care, the average person entering publicly-funded treatment has been in treatment before and is likely to return to treatment again. More work is needed to understand the decades-long course of addiction, treatment and recovery. The proposed study is designed to test specific hypotheses from a bio-psycho-social-spiritual model used for people with other chronic conditions in order to develop testable strategies for more effectively managing recovery over time. The study will expand from 5 to 10 years a longitudinal study of 1326 participants sequentially admitted to a treatment. The sample was stratified by level of care (outpatient, intensive outpatient, methadone maintenance, halfway houses, short-term residential, long-term residential) to ensure a range of substance use disorders and stage of addiction/treatment career. The participants are 59% female and 87% African American. Using a comprehensive assessment package, we conducted follow-up interviews at 6 months, 18 months, 2, 3, 4 and 5 (half) years achieving follow-up rates of 93% or more per wave. The specific aims are to: 1) examine the association between multiple treatment episodes, relapse, and recovery patterns over the course of 10 years; 2) evaluate individual differences that may moderate one's ability to initiate and sustain recovery, such as, psychiatric comorbidity, personality, and gender; 3) explore the extent to which treatment or other forces change mediators of recovery, such as changes in motivation, coping strategies,
Studies 91
spirituality, social networks, and physical recovery environment; and 4) evaluate the extent to which sustained recovery and attenuated substance use reduce the long-term consequences associated with substance use, including illegal activity, physical or mental illness, expensive service utilization, and death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERFORMANCE IMPROVEMENT
MEASUREMENT
FOR
TREATMENT
Principal Investigator & Institution: Nemes, Susanna A. Vice President of Tobacco, Drugs and Alc; Danya International, Inc. 8737 Colesville Rd, Ste 1200 Silver Spring, MD 20910 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: It is anticipated that Congress will move regulation of methadone treatment programs to adopt an accreditation model in the future. The center for Substance Abuse Treatment (CSAT), the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), and the Rehabilitation Accreditation Commission (CARF) have participated in a joint study to determine feasibility of an accreditation model. Preliminary findings show that programs are indeed able to meet accreditation requirements. Danya International, Inc. developed the conceptual framework for a Performance measurement for Treatment Improvement (PMTI) Web-based application in Phase I of this project. The unique benefits of this system to methadone treatment programs include, but are not limited to, the following: presents accreditation guidelines; provides sample plans, policies, and procedures; provides access to automated performance measurement tools; provides data reports and analysis; compares local, state/county, and national benchmark data; guides staff through a quality improvement (QI) process; and provides ready-to-use QI tools and techniques. Danya is proposing to develop and program this Web-based application in Phase II. Specific aims of the project will be to complete the architecture design, complete the content development of the PMTI system, program the system using Web-based technologies, beta test the system, and conduct a users' assessment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARACOKINETIC INTERACTIONS BETW ANTI HIV PROTEASE INHIB & DRUGS OF ABUSE Principal Investigator & Institution: Unadkat, Jashvant D. Professor; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001 Summary: The goal of this project is to test the hypothesis that when the anti-hiv protease inhibitors are coadministered with drugs of abuse, clinically significant pharmacokinetic drug interactions will result. We will test this hypothesis in the macaques using a representative protease inhibitor, ritonavir which is a potent inhibitor of both cytochrome p450 3a4 and the multidrug resistance efflux pump, p glycoprotein. The drugs of abuse that we will test will be morphine and methadone.. Specifically, our studies will test the major hypothesis that ritonavir will increase the concentrations of the narcotics in the cns by inhibiting their efflux via the p glycoprotein located at the blood brain barrier. In studies that we will conduct to test the above hypothesis we will also test the following subhypothesis. Ritanovir will increase the clearance of morphine to its glucuronide metabolites by induction of ugts. The disposition of ritonavir will be unaffected by narcotics. Studies will provide important data in a representative animal
92 Methadone
model to determine if studies should be conducted in the clinic to conform the presence of these interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOGENETICS OF METHADONE Principal Investigator & Institution: Devane, Lindsey C. Professor; Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 05-APR-2001; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract): Methadone is used as a maintenance treatment for opiate addiction and is the standard of care in the management of the pregnant opiate-addicted woman. Maternal methadone dose at delivery and the severity of neonatal withdrawal are closely related. Thus, methadone dose is a critical factor determining both maternal health and birth outcome. Most dosage regimens for methadone are empirical, titrating dose against withdrawal symptoms and, where appropriate, on the history of opiate use. Despite the use of methadone for nearly 50 years, details of its pharmacokinetics are surprisingly incomplete. A linear relationship has been reported between methadone dose and drug concentration in plasma but drug dose explains less than 50 percent of the variability. Methadone is marketed as a mixture (50:50) of 2 enantiomers called (R)-methadone and (S)-methadone, but (R)methadone accounts for nearly all of the opioid effects of the racemic dose. The disposition of methadone appears to be stereoselective and under genetic and environmental control. The pharmacogenetic contribution to methadone's disposition has received little study. Accordingly, a three-year dual-site, collaborative ROl study is proposed to define the major pharmacogenetic variables that influence the disposition of methadone in women. The major determinants to be studied include 1) gender, 2) ethnic origin (Africian-American vs. Caucasian background), 3) enantioselective metabolism; 4) plasma protein binding of methadone's enantiomers, 5) genetically determined phenotype of alpha1-acid glycoprotein (AGP), 5) the cortisol ratio as a surrogate marker of cytochrome P-450 (CYP) 3A4 activity, and 6) genotype of CYP2D6. A rigorous pharmacokinetic study of methadone disposition will be completed in healthy volunteer women and the results compared to healthy men. Correlations will be sought between the pharmacokinetics of methadone's enantiomers and effect measures shown in our preliminary data to be highly related (pupillary constriction, oral temperature, blood glucose concentration). Demographic and pharmacokinetic data will be obtained from 600 women (240 in Charleston and 360 in Cincinnati) receiving methadone maintenance. A population pharmacokinetic model will be constructed and tested to predict plasma concentrations of active (R)-methadone before and during pregnancy. The goals of this research are to describe the major pharmacogenetic factors which influence methadone concentration in women, and through pharmacokinetic analyses, to form a clearer understanding of the doseconcentration-effect relationship of methadone in a special population at risk, the pregnant opiate-addicted woman. This study will form the basis for subsequent studies which should provide a more rational basis for dosing of methadone in pregnant addicts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOKINETIC EVALUATION OF METHADONE Principal Investigator & Institution: Friedland, Gerald;; Yale University 47 College Street, Suite 203 New Haven, CT 065208047
Studies 93
Timing: Fiscal Year 2001 Summary: This study will use a controlled, open-label, crossover design to characterize the pharmacokinetics of methadone during concomitant administration with Combivir in opiate-dependent HIV negative individuals. Subjects must be enrolled in a certified methadone maintenance program, during which the current methadone dose has remained unchanged for 30 days prior to enrollment into this study. Methadone-treated subjects will serve as their own control for the methadone pharmacokinetic analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOKINETICS OF (R,S)-METHADONE IN HUMANS Principal Investigator & Institution: Boulton, David W.; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOLOGICAL PLASTICITY IN HUMANS Principal Investigator & Institution: Eisenach, James C. Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, NC 27106 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: A major aim of this Center is to perform translational clinical research closely linked to advances in fundamental knowledge on pain pharmacology, generated in each of the laboratory Projects. As such, a major focus and goal of Project V is to provide continuous interaction between laboratory and clinical investigators and projects. This process is aimed at refining both the laboratory and clinical hypotheses and to generate novel, testable concepts. All clinical protocols within this Center are designed, implemented, analyzed, and communicated internally by Project V. This includes proper power analysis, use of innovative study designs, collection of additional experimental data to support new methodologies, support for regulatory agency application, both at the institutional and federal level, consistent application of psychophysical testing, and standardization of methods to allow efficient comparison of results across studies. Dr. Rauck will be primarily responsible for the studies in volunteers and postoperative patient, Dr. Tobin will be responsible for the PET studies, and Dr. Coghill for psychophysical testing across all studies. Project V will examine, in four clinical trials, hypotheses generated by Projects I-IV, as well as its own hypotheses in psychophysics from Dr. Coghill. Included in these trials will be critical testing of the applicability of new methodology (i.e., a novel, more efficient, and clinically relevant approach to the study of analgesic drug interactions); examination of the predictive value of results in experimental models of pain in normal volunteers to subacute and chronic clinical pain settings; and determination of the contribution of hypersensitivity to the overall pain experience in patients following surgery and those with neuropathic pain. Unique pharmacologic tools available only at this institution will be utilized in these trials, and these trials will significantly advance the aims of the Center and our understanding of the pharmacology of pain in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOLOGICAL STIMULANT ADDICTION
REPLACEMENT
STRATEGIES
FOR
Principal Investigator & Institution: Spealman, Roger D.; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2001 Summary: The overall objective of this program is to identify candidate medications that may function as pharmacological replacements for abused stimulants Synthetic efforts, conducted by H M Deutsch, Ph D , Georgia Institute of Technology, focus on derivitization of two indirect dopamine agonists, methylphenidate and the novel bicyclooctane LR-5182 The aim is to modify the structures of these compounds to generate potent, long-lasting drugs that substitute for cocaine and may thus prevent craving and withdrawal symptoms induced by drug abstinence (analogous to methadone for the treatment of heroin abuse) During the last project period we evaluated several structural derivatives of methylphenidate for their capacity of mimic the discriminative stimulus effects of cocaine in a manner predictive of cocaine-like subjective effects Monkeys were trained to discriminate a behaviorally active dose of cocaine (0 3 mg/kg, i m ) from vehicle using a two-choice drug discrimin ation pro cedure Under test conditions, cocaine, methylphenidate and a number of N-substituted and aromatic ring-substituted derivatives of methylphenidate induced dose-related increases in drug-appropriate responding reaching r 90% responses on the cocaineassociated lever Of these compounds dichloromethylphenidate, dichlororitalinol and dichlororitalinol methyl ester were more potent and had slower onsets and longer durations of action compared either cocaine or methylphenidate, suggesting that they may be suitable candidates for further evaluation in drug self-administration studies scheduled for the forthcoming year Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PLACE DETOXIFICATION
OF
LOW-DOSE
NALTREXONE
IN
OPIATE
Principal Investigator & Institution: Mannelli, Paolo; Psychiatry and Human Behavior; Thomas Jefferson University Office of Research Administration Philadelphia, PA 191075587 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): This study is being submitted for review under the R21 (exploratory grant) mechanism, Its purpose is to explore whether the addition of very low doses of naltrexone to a methadone tapering schedule for opiate detoxification is safe, decreases withdrawal intensity and enhances patient treatment compliance. Although many different techniques for opiate detoxification have been employed, there is a continuing search for more effective approaches to reduce the duration and discomfort of withdrawal. Recent attempts have included the use of opiate antagonists to induce "ultra rapid" detoxification. However, the resulting need for heavy sedation or anesthesia to control withdrawal intensity and the increased possibility of medical complications has discouraged and limited the use of this approach. By contrast, there is experimental evidence that very low doses of naltrexone administered in the presence of opiates has analgesic and dependency reducing properties, suggesting that the use of very low dose naltrexone in the clinical management of opiate detoxification might be a useful strategy. To test this hypothesis, 360 volunteer opiate dependent subjects, admitted to the inpatient detoxification program of a community hospital and placed on a 4-day detoxification schedule, will be randomly assigned to receive one of three
Studies 95
different low-dose naltrexone schedules or placebo in addition to their routine methadone tapering treatment. The four groups will be compared with respect to behavioral, biological and subjective withdrawal signs and symptoms, detoxification completion rates, acceptance of referral to outpatient treatment, and one and seven day post-detoxification follow-up evaluations. If the administration of low-dose naltrexone (antagonist) at the same time as methadone (agonist) is found to be more effective than placebo in reducing withdrawal discomfort, the findings will have clear treatment implications and raise important questions about the mechanisms of opiate agonist and antagonist interactions at the receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRECLINICAL DEVELOPMENT OF DRUGS FOR STIMULANT ABUSE Principal Investigator & Institution: Deutsch, Howard M. Principal Research Scientist; School of Chemistry & Biochem; Georgia Institute of Technology 225 North Ave Nw Atlanta, GA 30332 Timing: Fiscal Year 2001; Project Start 20-JAN-1999; Project End 30-NOV-2003 Summary: The purpose of this work is to synthesize and test compounds which will be useful therapeutic agents in the treatment of stimulant abuse. Synthetic efforts will center around the derivatization of two indirect acting dopamine agonists, methylphenidate and LR-5182 (a bicyclooctane). The aim is to alter their basic structures in such a manner as to generate either (1) potent, long-lasting agonists which will substitute for the abused (analagous to methadone in the treatment of heroin addiction), (2) partial agonists or mixed agonist-antagonists which will lessen the subjective effects of the abused stimulant, but exhibit a mild stimulant effect of their own; or (3) antagonists, which will block the subjective effect of the abused stimulant, but have no intrinsic stimulant activity. The compounds will be evaluated using a multi-tiered battery of tests. The first level will consist of the in vitro determination of potency to block dopamine uptake and [3H]WIN 35,428 binding, selectivity for the dopamine transporter, and right-shift of the cocaine inhibition curve against dopamine uptake Based on the outcome, some compounds will progress to the second level of testing, where their ability to substitute for and/or antagonize cocaine in drug discrimination and conditioned place preference tests in rats will be assessed. Compounds judged to have therapeutic potential at this point will then advance to testing in primate selfadministration and drug- discrimination paradigms. Although the aim is to develop agents for the treatment of stimulant abuse, the findings may also have application in other disorders involving dopaminergic pathways, including attention deficit disorder, Parkinson's disease, Tourette's syndrome, and schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PRENATAL COCAINE EXPOSURE EFFECTS ON NEONATAL METHODONE WITHDRAWL Principal Investigator & Institution: Mayes, Linda;; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTING DEPRESSION IN MMT PATIENTS ON INTERFERON Principal Investigator & Institution: Ramsey, Susan E.; Rhode Island Hospital (Providence, Ri) Providence, RI 02903 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2006 Summary: (provided by applicant): To date, the use of psychosocial interventions to prevent the major depressive episodes that are commonly precipitated by antiviral treatment for the hepatitis C virus (HCV) has been unexplored. However, cognitivebehavioral treatments for depression (CBT-D) have demonstrated efficacy in a number of different populations, including substance abusers and individuals with medical problems, and have been found to be efficacious in the prevention of depression. The long-term objective of this research program is to improve depression prevention options for methadone maintenance treatment (MMT) patients undergoing interferon (IFN) treatment for hepatitis C by developing and establishing the efficacy of a CBT-D intervention tailored to this population. Furthermore, we seek to advance knowledge of the relationship between depressive symptoms and IFN treatment adherence and illicit drug use relapse. In the present application, we propose to develop a CBT-D intervention tailored to meet the needs of MMT patients undergoing antiviral treatment for hepatitis C. In the first phase of this project (Year 1), we will develop and pilot the intervention with 20 patients. In the second phase of the project (Years 2 and 3), we will conduct a preliminary, randomized trial with 60 MMT patients to examine the efficacy of the CBT-D intervention relative to the relaxation training (RT) control condition that equates for therapist contact time. We expect that, relative to the RT condition, participants randomized to the CBT-D condition will have decreased likelihood of depression-related antiviral treatment failure, will report lower levels of depressive symptoms, will complete more IFN injections, will have lower HCV RNA levels, and will have fewer illicit drug use days. If the efficacy of this intervention can be established in this trial and in subsequent clinical trials, MMT patients who elect to undergo antiviral therapy will have a valuable adjunct or alternative to the use of antidepressants to prevent depression. If found to be efficacious, this intervention will maximize the receipt of IFN treatment by MMT patients, thereby aiding in the prevention of liver failure, hepatocellular carcinoma, and liver-related death among those with HCV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT
PRISM--COMORBIDITY
DIAGNOSIS
FOR
DRUG
ABUSE
Principal Investigator & Institution: Hasin, Deborah S. Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032 Timing: Fiscal Year 2001; Project Start 15-MAR-1998; Project End 28-FEB-2003 Summary: (Applicant's Abstract): Psychiatric comorbidity, particularly depression, occurs often in substance abusers, and is associated with poor outcome. However, previous diagnostic instruments have been unreliable, controversy has surrounded the concepts of comorbidity diagnosis, and results of treatment studies have been inconsistent. In particular, questions persist on whether a treatment-responsive depressive disorder exists in non-abstinent substance abusers. For treatment research to begin to accumulate meaningful results on substance abuse comorbidity, concepts and diagnoses must be clear and reliable. To begin to address this problem, we developed the DSM-111-R Psychiatric Research Interview for Substance and Mental Disorders (PRISM), which showed very good test-retest reliability for primary major depression
Studies 97
and other DSM-111-R mental disorders in substance abuse and psychiatric patients. To address the problem of current DSM-IV diagnosis of depression and other disorders in non-abstinent substance abusers, we developed a new version of the PRISM. This version uses phenomenologically-oriented methods for differentiating between primary disorders, substance-induced disorders, and the expected effects of intoxication/withdrawal. These PRISM methods were carefully designed to be consistent with DSM-IV. A reliability and validity test of the new PRISM is needed, with special focus on the differentiation between current primary depression, substanceinduced depression and expected intoxication/withdrawal effects. We propose such a study in 510 methadone maintenance and dual diagnosis psychiatric patients. Interviews will be conducted by clinicians. The sample will allow for separate reliability coefficients for each site. Subjects will be sampled to ensure stable reliability estimates for African-American as well as white patients. The data will also allow tests of the effects of demographic, clinical and process factors on reliability. An initial validity study will also be conducted, focused on the PRISM differentiation between primary major depression, substance-induced major depression, and the expected effects of intoxication/withdrawal. For the validity study, we will use family history and inperson expert psychiatrist evaluation of the need for antidepressant treatment as validators. If the PRISM shows good reliability and validity, it will offer a significant methodological advance for treatment research in substance abusers with psychiatric comorbidity. The study results will provide empirical evidence that is likely to be useful in formulating DSM-V. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEASE INHIBITOR/METHADONE METABOLISM IN HIV INFECTION Principal Investigator & Institution: Sacks, Henry;; Mount Sinai School of Medicine of Cuny New York, NY 10029 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEASE INHIBITORS AND METHADONE METABOLISM IN HIV + Principal Investigator & Institution: Gerber, John G.; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REDUCING HIV RISK IN METHADONE-MAINTAINED PATIENTS Principal Investigator & Institution: Avants, Sandra A. Assistant Professor; Apt Foundation, Inc. 1 Long Wharf Dr, Ste 321 New Haven, CT 06511 Timing: Fiscal Year 2001; Project Start 30-SEP-1993; Project End 31-DEC-2002 Summary: Our recently completed randomized clinical trial of two intensities of psychosocial intervention in methadone-maintained programs (MMPs) suggested that standard methadone maintenance enhanced by the addition of a weekly coping skills training group together with as-needed referral to other services was comparable to a
98 Methadone
25-hour per week Day Treatment Program in reducing illicit drug use, and was provided at one- third the cost. However, in the absence of a standard methadone maintenance comparison group, no definitive policy recommendation could be made concerning the need for MMPs to enhance standard care. Other findings suggested that methadone-maintained patients may have social and cognitive deficits that may influence HIV risk reduction efforts, and that both standard and enhanced MMPs would benefit from the inclusion of an HIV risk reduction intervention. Based on these findings, we developed: (a) a single-session HIV risk reduction intervention based on NADR Project recommendations that could be included in standard methadone maintenance and repeated as a post- treatment "booster" session to reduce the risk of relapse; (b) a manual- guided weekly coping skills training group that could be included in enhanced methadone services using cognitive remediation and motivational enhancement strategies to teach HIV risk reduction skills; and (c) a comprehensive risk assessment battery which includes assessment of risky behaviors, and the processes underlying these behaviors, such as HIV/AIDS knowledge, motivation, and objective measures of behavioral skills. This competing renewal requests four years' additional support to continue our research to identify the most cost-effective level of ancillary psychosocial treatment for reducing illicit drug use and other HIV risk behaviors in MMPs by conducting a 12-week randomized clinical trial in which 224 methadonemaintained patients will be randomized to one of four cells in a 2 (standard/enhanced MMP) x 2 (booster/no booster) factorial design. Both clinical efficacy and cost will be determined, and objective measures will be employed to assess change in illicit drug use and other HIV risk behavior at post-treatment, and at a 6-month follow-up. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RELATIONAL PARENTING INTERVENTION FOR DRUG ABUSING FATHERS Principal Investigator & Institution: Mcmahon, Thomas J.; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: As in most other social service systems, the status of men as fathers is not typically acknowledged in the conceptualization and delivery of substance abuse treatment. Although there has been extensive discussion of the need for parent intervention for drug-dependent mothers, there has been little consideration of the need for complementary intervention for drug-dependent fathers. Consequently, this Stage I psychotherapy development project will focus on the development, manualization, and initial evaluation of a relational parent intervention for methadone- maintained fathers with minor children and ongoing abuse of opioids, other drugs, or alcohol. This 26-week group psychotherapy will be grounded in a developmental-ecological perspective on parenting, and the intervention will be structured to move men through a process of behavior change designed to improve parent-child relationships and decrease substance use. Throughout the treatment, motivational and interpersonal techniques will be used to (1) highlight ways substance abuse interferes with parenting, (2) facilitate relationship building, and (3) explore ways commitment to parenting might be used to support abstinence. Over the course of 36 months, a systematic, goal-oriented approach to the development of psychosocial treatments will be used to realize four specific aims. First, guidelines outlined by Carroll and Nuro (1997) will be used to develop a comprehensive treatment manual that will define the intervention and guide delivery to the target population. Second, procedures outlined by Waltz et al (1993) will be used to develop psychotherapy process measures needed to document (1) adherence to the treatment
Studies 99
protocol, (2) the clinical competence of group leaders, and (3) critical dimensions of the behavior change process. Third, content drawn from a preliminary group done with eight methadone-maintained men will be used to develop educational materials for use with clinicians, and procedures similar to those outlined by Rounsaville et al. (1984) will be developed to guide the selection, training, and supervision of group leaders. Finally, a randomized pilot study done with 64 methadone- maintained fathers will be used to evaluate the feasibility, discriminability, and potential efficacy of the proposed intervention when compared with a manualized version of group drug counseling that best represents treatment as usual. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RELATIONAL PARENTING THERAPY FOR OPIOID ABUSING MOTHERS Principal Investigator & Institution: Luthar, Suniya S. Professor; Apt Foundation, Inc. 1 Long Wharf Dr, Ste 321 New Haven, CT 06511 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 30-NOV-2002 Summary: (Applicant's Abstract) The proposed study will involve a randomized clinical trial of the Relational Parenting Mothers' Group, (RPMG), an intervention designed for opioid abusing women with children less than 14 years of age, which was manualized and pilot tested as part of a Phase I study (P50-DA09241). This intervention was developed in recognition of the substantial psychosocial risks faced by substance abusing mothers and their offspring, and the notable lack of parenting interventions currently available for addicted mothers with children past the infancy years. Based on developmental psychopathology perspectives on resilience, this integrative treatment addresses multiple levels of adversity (individual, community, and family) faced by drug abusing mothers: risks that typically result in negative parenting behaviors and psychosocial distress among the mothers and concomitantly, psychiatric disturbance among their offspring. RPMG is a structured treatment, entailing 24 weekly group sessions of 1 1/2 hours each. Preliminary data collected in the Phase I study have attested to the promise of RPMG in terms of diverse parenting behaviors and psychiatric outcomes among both the mothers and their children, and in the proposed study, we seek to conduct a randomized clinical trial in which RPMG will be compared with Recovery Training (RT; a manualized treatment resembling standard drug counseling). Both RPMG and RT interventions will be offered as supplements to treatment regularly offered at the methadone clinics. Eighty methadon-maintained mothers will be randomized to each of the two treatment conditions, yielding a total sample size of 160. Multiple-method, multiple-informant assessments will be obtained to measure salient outcomes, including reports from the mothers and their children, and from the mothers' clinicians and the children's teachers. The following specific goals will be addressed within this study: (1.) To evaluate the comparative effectiveness of RPMG versus RT in terms of improvements in (a.) mothers' parenting behaviors and attitudes, and their psychiatric disturbance; as well as and (b.) in their children's levels of symptomatology and everyday social competence; (2.) To evaluate the durability of RPMG treatment gains, as well as potentially delayed treatment effects, via follow-up assessments of both mothers and children six months after the active phase of RPMG treatment; and (3.) To examine ways in which specific maternal characteristics relate to treatment success. Guided by previous research, these characteristics will include (a.) intelligence (b.) sensation seeking (c.) ethnicity; and (d.) readiness for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REPRODUCTIVE CONSEQUENCES OF PUBERTAL MORPHINE ABUSE Principal Investigator & Institution: Byrnes, Elizabeth M. Environmental/Population Hlth; Tufts University Boston Boston, MA 02111 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): The present proposal will study the impact of opiate abuse during puberty on future reproductive health. In both the rat and human, puberty is a period during which the reproductive cycles and daily hormonal rhythms begin to emerge. Because endogenous opioids mediate some of these changes, artificially elevated levels of opioids during this period can interfere with reproductive development. While some of the acute effects of opiates like morphine, heroin, and methadone in pubertal females have been delineated, the long-term effects of opiate abuse during the tumultuous pubertal period are unknown. Recent preliminary studies indicate that administering morphine to female rats around the time of puberty results in reproductive alterations that can be observed weeks after drug withdrawal. Specifically, while these females give birth to healthy pups, the rate of growth of their offspring is reduced. Moreover, there appears to be a decrease in the suckling-induced release of prolactin. Given the positive correlation between prolactin secretion and milk yield, a reduction in prolactin secretion could underlie reduced pup growth. Using a chronic increasing dose regimen of morphine (twice daily injections from age 30 to 50 days old), the present set of studies will examine the possible neuroendocrine alterations that may subserve both the decrease [in] suckling-induced prolactin secretion and decreased pup growth. These include examination of the level of prolactin content and message in the anterior pituitary, the sensitivity of the mu-opioid and D2 dopamine receptor subtypes to modulate prolactin secretion, and the expression of prolactin receptors in the mammary gland. In addition, the longevity of alterations in sucklinginduced prolactin secretion and reduced pup growth will be examined. The long-term objective of this proposal is to use these studies as an animal model of drug addiction in adolescent females. Given the recent rise in the number of adolescent girls abusing heroin, these studies will provide information on some of the potential reproductive consequences that may arise in the future for girls addicted to opiates during this sensitive developmental period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RESEARCH ON TREATMENT AND PREVENTION OF IV DRUG ABUSE Principal Investigator & Institution: O'brien, Charles P. Prof/Vice Chair of Psychiatry; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 30-JUN-2002 Summary: This research Center was originally funded in 1987. The Center funding provided support for a Core Unit to coordinate Center activities and initiate new projects using flexible funding for pilot projects. Specific research projects were also funded within the Center. The "center concept" has functioned very well in that the Center funding has been used to stimulate growth and productivity. Not only have the specific projects been completed, but new projects which began as pilot projects were completed and others were developed into new grant applications. The educational program has grown and there now is an institutional fellowship program that has attracted high quality applicants including a high proportion of physicians. An Institutional Physician Scientist Development program has just been awarded for new
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faculty level development. A 21 hour required course on substance abuse for medical students has been instituted. A Treatment Research Unit has been created that has expanded our research population to the non-veteran community. We have just been awarded an Instrument Development Center that will coordinate with this Research Center to facilitate the development of new clinical research instruments. A Scientific Advisory Board was formed and it has met annually since the founding of the Center. Over the past five years, the Center staff have published 145 research reports, 79 reviews and 2 books. Studies completed by Center staff have been utilized by policy markers in Congressional testimony. These include a controlled study of the effects of three levels of psychosocial intervention in combination with methadone treatment, a longitudinal study of HIV conversion rates in opiate addicts in and out of treatment, a study of the efficacy of inpatient and outpatient rehabilitation for cocaine dependence and a controlled study of the effects of naltrexone treatment on reincarceration rate for Federal probationers. The present application is for an additional five years of funding. In addition to continuing the Core Unit at approximately the same level, we are requesting funding for new projects that will address current problems of intravenous drug abuse. The first section addresses the biological basis of relapse to drug dependence. The first utilizes new brain imaging techniques in human subjects to extend our prior findings concerning conditioning in cocaine dependence. The second combines microdialysis and behavioral techniques in an animal model of cocaine dependence. The third project continues our work on endogenous opioids in a series of proposed studies of tolerance and dependence using animal models and isolated cells and in studies of human opiate addicts at specific stages of the addiction cycle. Section 2 consists of three projects dealing with relapse to drug dependence. The first compares levels of psychosocial intervention in combination with medication for the treatment of cocaine dependence. The second compares two types of aftercare over 24 months of followup for the treatment of cocaine dependence. The third study examines the relationship between psychopathology and treatment response in women substance abusers over a two year followup period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROTONIN TREATMENT OF COCAINE DEPENDENCE Principal Investigator & Institution: Strain, Eric C. Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 31-MAR-2006 Summary: (Applicant's Abstract) This is a competitive renewal application to continue to study the efficacy of serotonergic medications in the outpatient treatment of cocaine dependence. The originally funded study examined tryptophan, the precursor of serotonin, in the treatment of cocaine abuse, and hence the grant was titled "Tryptophan and Behavior Therapy for Cocaine Abuse." Since this renewal shifts focus from tryptophan to another medication that alters serotonin functioning (fluoxetine), it has been re-titled "Serotonin Treatment of Cocaine Dependence." While several studies have reported on clinical experience in the use of fluoxetine for the treatment of cocaine use, most of these studies have methodological limitations (e.g., small sample sizes, heterogeneous study populations, failure to ensure compliance in taking medication, inadequate patient motivation). Importantly, there have now been several well conducted, controlled studies suggesting fluoxetine can be effective in the treatment of cocaine abuse - when medication compliance is assured, and when it is combined with incentives that provide motivation to stop using cocaine. Further, pilot subjects tested in our clinic with the currently proposed methods have shown positive responses. This
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proposal builds upon prior studies in its design and extends the methods used with our pilot subjects. It also continues the theme begun with the first study - that is, enhancing serotonergic functioning as a means of decreasing the reinforcing effects of cocaine. The current proposal again tests medication efficacy in the context of voucher incentives that provide motivation to stop cocaine use, but now has new design features in response to experience from the first clinical trial. Specifically, this proposal is to test fluoxetine in methadone maintained patients with concurrent cocaine dependence. There are several reasons for utilizing methadone maintained patients: compliance taking medication can be assured, retention rates are high, and concurrent cocaine dependence is common. The design is a 2 x 2, with patients randomly assigned to receive either double blind fluoxetine or placebo, and either voucher incentives or no voucher incentives. Voucher incentives can be effective in decreasing cocaine use, but studies have shown only about one-half of patients respond to this intervention. The main hypothesis to be tested in this study is that the combination of fluoxetine with vouchers will produce enhanced effects on decreasing cocaine use, compared to outcomes produced by the treatments alone. The principal logic underlying this study is that fluoxetine will weaken (but not necessarily eliminate) cocaine effects, and that this will translate into higher success rates under a behavior therapy that provides incentives for abstinence. These results will provide valuable new information about the ability of fluoxetine to enhance the effectiveness of an effective behavioral treatment intervention, and can lead to new and innovative treatment approaches for cocaine abusing patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SERVICE USE BY MEN ON METHADONE COMMITING PARTNER ABUSE Principal Investigator & Institution: Wu, Elwin; None; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): In response to NIDA PA-01-097, this application details an R03 project that focuses on the service utilization of formal healthcare, mental health, and social services for men on methadone who perpetrate intimate partner violence (IPV). The proposed study will examine barriers and enhancers of service utilization among male methadone maintenance treatment program (MMTP) clients who perpetrate IPV. Drug-involved men who perpetrate IPV lie at the heart of two critical public health issues, drug abuse and IPV, that exact enormous financial and societal costs. Perpetrators of IPV represent a significant proportion of drug-involved men that may have a greater number and/or unique spectrum of service needs that differ from non-violent, drug-involved men and that remain unmet due to lack of service utilization. These needs extend beyond drug abuse and IPV to include mental and physical health and other social service needs. Most of the prior studies with perpetrators of IPV have been carried out with samples obtained from batterers intervention programs. Thus, service utilization among a more general population of men who perpetrate IPV remains unexplored. The proposed research will build upon findings from the Men's Health Project (MHP), an ongoing NIDA-funded study (PI: ElBassel) to examine over time the relationships among drug abuse, IPV, and HIV-related risks among a random sample of 355 men attending MMTPs in New York City (NYC). We propose to extend the MHP by reinterviewing MHP participants who perpetrated IPV to study factors that impact their service utilization, an area not addressed in the parent study. The proposed study also includes a qualitative inquiry with MMTP service providers to understand MMTP service providers' perspectives on factors that
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impede or promote service utilization among their male clients who perpetrate IPV, as well as identify potential targets of change in the MMTP service delivery system. Aims, hypotheses, and measurements in the proposed study are guided by the Network Episode Model, which conceptualizes utilization of formal services as a series of behaviors influenced by individual/social context, social network, and service system factors. This study will provide pilot findings for the development of an R01 study testing the efficacy of an intervention designed to increase service utilization among men attending MMTPs who perpetrate IPV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SERVICES RESEARCH ON INTERIM OPIOID MAINTENANCE Principal Investigator & Institution: Schwartz, Robert P. Medical Director; Friends Research Institute, Inc. Box 10676, 505 Baltimore Ave Baltimore, MD 21285 Timing: Fiscal Year 2001; Project Start 20-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant) Long waiting lists for entry into opioid maintenance treatment (OMT) exact a tremendous cost on both heroin-dependent people and society. This three-year health services research study, conducted within the context of a mobile opioid maintenance treatment program, seeks to examine the ability of interim maintenance treatment to facilitate entry into full service OMT programs, and to reduce heroin and cocaine use, HIV risk, and criminal behavior of heroin-dependent people on waiting lists in Baltimore City. Adult heroin-dependent subjects (N = 360) who meet FDA criteria for OMT and for whom no treatment slot is available, will be randomly assigned to either: a) interim treatment with LAAM, an opioid agonist that can be administered thrice weekly; b) interim treatment with methadone;; or c) standard waiting list condition (no treatment control group). Interim treatment will consist of LAAM or methadone therapy, with counseling on an emergency-only basis. All participants will be registered on the mobile program's waiting list for full service OMT and will be encouraged to call the 11 existing full service OMT programs in Baltimore City for waiting list placement and treatment entry. Following FDA guidelines, all interim treatment subjects who have not gained entry into full service OMT programs by 120 days from study entry will be admitted to one of Baltimore City's OMT programs, by explicit agreement with the Baltimore City's substance abuse authority. Control subjects will gain entry through the usual waiting list procedures in Baltimore City. Outcome will be assessed by measuring the percentage of subjects who enter full service OMT programs, as well as changed in participants' drug use, HIV-risk behavior, and criminal activity, with assessments obtained at baseline, at the time of full service treatment entry or 120 days from baseline for those subjects who do not enter full service treatment, and six months thereafter. We hypothesize that subjects receiving interim opioid maintenance treatment will have superior outcomes to waiting list controls. Furthermore, we hypothesize that LAAM interim subjects will have superior outcomes to methadone interim subjects, because LAAM's reduced clinic reporting schedule will facilitate interim program adherence and retention. The results of this study will provide a definitive determination of the effectiveness of a strategy to improve the OMT service delivery system by reducing barriers to treatment entry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SMOKING CESSATION AMONG METHADONE MAINTAINED PATIENTS Principal Investigator & Institution: Stein, Michael D. Professor of Medicine and Community Hea; Rhode Island Hospital (Providence, Ri) Providence, RI 02903
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Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: Opiate dependent persons who are successfully engaged in the treatment of their primary drug of addiction often continue to use other drugs such as nicotine. With the high prevalence of smoking in this population, treatment providers are recognizing that many of those they help recover are now dying of smoking-related illnesses, including cancer. Recent surveys indicate that persons enrolled in methadone maintenance treatment programs are interested in receiving smoking cessation treatment, particularly as treatment facilities go smoke-free through voluntary efforts or JCAHO mandates. The long-term aim of our proposal is to advance knowledge and produce interventions to help achieve optimal dissemination of stroking cessation strategies for those usually deprived of such programs with dual diagnosis of opioid dependence and nicotine dependence. Using a two-group design, we will enroll 408 methadone-maintained cigarette smokers from two methadone treatment programs in Rhode Island. The specific aims are: A.1. To test, in combination with the nicotine patch, the incremental efficacy of a maximal, tailored and sustained behavioral treatment over a minimal treatment in the setting of a methadone maintenance program. The defined population comprises low income, less educated smokers who will vary in their level of motivation to quit smoking. Patients will be randomly assigned to one of two treatments.(a) Nicotine patch prescription plus brief nurse advice and followup.(minimal treatment; and (b) Nicotine patch prescription, brief nurse advice and follow-up, with the addition of a tailored motivational intervention, a behavioral skills counseling session for smoking cessation, and continued telephone counseling (maximal treatment). We hypothesize that 6 month 7-day point prevalence quit rates will be 4% and 12% in each of the two treatment groups, respectively. A2. To test the effects of the treatments on intermediate variables including motivation to quit smoking, cognitive behavioral mediators of motivation and intention to quit (e.g. self-efficacy, pros and cons of smoking, perceived vulnerability to illness, and perceived ability to prevent illness by quitting smoking), frequency of patch use, and number of quit attempts. We hypothesize that these variables will improve from baseline to 6 months as a function of treatment intensity. A3. To test the effects of the treatments on methadone treatment outcomes including methadone dose changes and continued use of illicit drugs, as measured by urine toxicologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TDM & DRUG INTERACTIONS IN HIVINFECTED SUBSTANCE ABUSERS Principal Investigator & Institution: Morse, Gene D. Chairman; Pharmacy Practice; State University of New York at Buffalo 402 Crofts Hall Buffalo, NY 14260 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): This application describes an innovative approach to the rapid assessment of complex drug interactions between protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs), and commonly prescribed medications including methadone, ethinyl estradiol, fluconazole, pravastatin, and fluoxetine in HIV-infected, substance abusers The proposed methodology employs a Therapeutic Drug Monitoring (TDM) program that will facilitate rapid determination of ART in subjects receiving multiple interacting medications Specific aims 1) Implement a TDM program that will establish a mechanism to investigate protease inhibitor (PI) and NNRTI pharmacokinetics in HIV-infected, substance abusers receiving ART, determine drug exposure parameters (Cmin, AUC) and inhibitory quotients (IQs), 2) Determine the pharmacokinetics of selected interacting medications (methadone, ethinyl estradiol,
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fluconazole, pravastatin, fluoxetine) in HIV-infected, substance abusers receiving ART, 3) Determine in vitro and ex vivo total and unbound plasma concentrations of protease inhibitors and NNRTIs in HIV-infected, substance abusers utilizing novel analytical approaches including HPLC, LC-MS-MS and capillary electrophoresis, 4) Develop and validate a capillary electrophoresis assay capable of enantiomeric separation to enhance the pharmacokinetic analysis of interacting medications, 5) Examine pharmacogenetic factors that may identify individuals at greater risk for insufficient or excessive systemic drug exposure while receiving complex regimens with multiple drug-drug interactions The proposed TDM-drug-drug interaction program integrates a comprehensive antiretroviral clinical pharmacology research group, an HPLC/LC-MS analytical facility, a pharmacometrics laboratory, a web-based TDM enrollment infrastructure, and four HIV clinical centers caring for substance abusers Innovative pharmacokinetic and pharmacodynamic modeling approaches to assess complex drug-drug interaction analyses of PI and NNRTIs from HIV-infected substance abusers and non-substance abusers will be conducted. Clinical sites will enroll subjects while drug measurement and data analysis will be conducted at the central pharmacology laboratory. These studies will provide insight into clinical interactions that face clinicians and patients today, and identify priority drug interactions that require more traditional pharmacokinetic trials to identify specific mechanisms of interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ECONOMICS OF POLYDRUG ABUSE Principal Investigator & Institution: Meisch, Richard A. Professor; Psychiatry and Behavioral Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: (Applicant's Abstract) This new application concerns the use of behavioral economics to analyze polydrug abuse. Two groups of 5 rhesus monkeys will be used in parallel studies of polydrug abuse. One group of monkeys will have access to methamphetamine and the other group will have access to methadone.. The delivery of drugs will be contingent upon the completion of fixed-ratio schedules. Under a fixedratio schedule delivery of the reinforcer is contingent upon making a fixed-number of responses. In the present application completion of fixed-ratio schedules will result in the delivery of 0.67 ml of liquid. Depending upon the experimental conditions, the liquid will be water or a solution of drug. Two liquid delivery systems will be present thereby giving the monkey a choice between liquids. In Study 1, either a solution of methamphetamine vs. water, or a solution of methadone vs. water will be present. The concentration of the drug solutions will be varied and also the number of response (i.e. fixed-ratio size) required per liquid delivery will also be systematically changed. The results will be plotted in terms of the drug amount consumed at different prices (i.e combinations of fixed-ratio size and drug concentration). In the next set of studies a series of drug pairs will be analyzed as the price for one drug is changed to different values and the price of the other drug is held constant. In these studies the monkeys will have the option of taking two drugs or just one drug or neither. The focus is on the interactions between intake of drug and their prices. The overall aim is to determine what combinations of drugs are taken when the cost of each drug is varied. The results will demonstrate a systematic and quantitative strategy for the analysis of polydrug abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THREE METHODS FOR COSTING METHADONE TREATMENT SERVICES Principal Investigator & Institution: Zarkin, Gary A. Director; Research Triangle Institute Box 12194, 3040 Cornwallis Rd Research Triangle Park, NC 27709 Timing: Fiscal Year 2003; Project Start 21-MAR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Managed care and reductions in government spending have placed great pressure on providers, payers, and researchers to demonstrate the cost-effectiveness and cost-benefits of drug treatment services. As a first step in these economic evaluations, the costs of specific treatment services must be estimated. Although much previous work has estimated drug treatment costs, only a very limited number of service cost estimates exist, and no study has evaluated the effect of alternative data collection methods on estimated service costs. Furthermore, no previous work has attempted to estimate the burden of collecting service cost data. Our proposed analysis evaluates three alternative methods for estimating service-level costs in methadone treatment programs. These three methods differ in how they collect staff time allocation across treatment services. The three alternative data collection methods are (1) surveying the clinic director (key informant), (2) surveying the clinic staff (staff informants), and (3) staff diaries for 1 week. Our analysis will assess the extent to which differences in the method used to collect the staff time allocation across alternative treatment services contribute to differences in service cost estimates. In addition, as part of the service cost evaluation, we will also estimate the costs of collecting the staff time allocation data for each of the three data collection methods. Implementation of these three estimation methods will occur in a sample of methadone clinics that were part of CSAT's Evaluation of the Methadone/LAAM Treatment Accreditation Project. To accomplish our research objectives, the specific aims of our analysis are to (1) develop a revised taxonomy of methadone treatment services and job types, (2) estimate the costs of specific treatment services, and (3) evaluate the sources of service cost variation. The research team has a strong track record estimating the costs of treatment, and extensive knowledge and insights into the fundamental issues involved in this research. At the conclusion of our proposed research project, we will understand the extent to which differences in collecting staff labor time affect estimates of treatment service cost, and we will have developed and implemented a revised service cost estimation methodology that will be applicable to all drug treatment modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSDERMAL BUPRENORPHINE FOR OPIATE ANTAGONIST THERAPY Principal Investigator & Institution: Nichols, L D.; Biotek, Inc. 21-C Olympia Ave Woburn, MA 01801 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JAN-2004 Summary: (provided by applicant): Opiate antagonist therapy is an important treatment for recently withdrawn narcotic addicts. Buprenorphine is a drug with mixed agonistantagonist properties, which eliminates physiological reinforcement by preventing any subjective reward from morphine-like drugs. Buprenorphine is very effective and is preferred by subjects to either methadone or naltrexone. BIOTEK proposes to improve buprenorphine therapy by developing a 3-day transdermal delivery system. A buprenorphine patch would avoid the inconvenience of frequent clinical visits, and steady maintenance of the agonist action of buprenorphine should motivate compliance by providing more positive reinforcement. BIOTEK has previously demonstrated high
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transdermal delivery rates for buprenorphine. Recent results from a study of human subjects using BIOTEK's injectable buprenorphine microcapsules suggest that effective opiate blockade can be maintained by a much lower buprenorphine dose rate than previously thought necessary. It is the purpose of the proposed program to develop an effective antagonist patch containing too little buprenorphine to be an attractive target for subversion or abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT FOR DUALLY DEPENDENT METHADONE PATIENTS Principal Investigator & Institution: Petry, Nancy M. Professor of Psychiatry; Psychiatry; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: A large proportion of methadone patients are dependent on multiple drugs. Alcohol is one drug that is frequently abused by methadone patients. The consequences of excessive alcohol use may include increased HIV risk-taking behaviors, psychosocial problems, accidental injury, and death. Despite the severity of the problem, a dearth of literature exists on treatment strategies for alcohol dependence in methadone patients. Only three controlled clinical trials have demonstrated significant reductions in alcohol use in this population. All three studies showed that an intervention in which disulfiram ingestion was necessary for methadone treatment reduced alcohol use compared to a standard, optional disulfiram condition. The two proposed studies will replicate and extend these findings. Specifically, Study 1 will assess whether disulfiram is necessary, or whether contingency management procedures on their own are sufficient, to reduce alcohol use, alcohol-related problems, and HIV risk-taking behaviors in alcohol dependent methadone patients. This study will compare three treatments: a treatment in which methadone dose is contingent upon disulfiram ingestion, a treatment in which methadone dose is contingent upon negative breath-alcohol samples (BACs), and a control treatment in which methadone dose is provided irrespective of BAC results. Study 2 will examine whether enhancing a treatment from Study 1 further improves outcomes. The study will compare: the most effective treatment in Study 1 (methadone contingent upon either disulfiram ingestion or negative BACs) and an enhanced version of that treatment in which both methadone dose and voucher incentives, exchangeable for retail goods, are contingent on either disulfiram ingestion or negative BACs. In the unlikely event that no differences are noted among the three conditions in Study 1, a treatment in which methadone dose and voucher incentives are contingent on disulfiram ingestion will be compared to the standard, non-contingent treatment. In total, 180 methadone maintained subjects will be randomly assigned to receive one treatment for a 3-month period. BACs will be assessed daily, urines will be screened for alcohol and illicit drugs twice weekly, and self-reports of HIV risk-taking behaviors will be collected weekly. Monthly interviews will assess psychiatric symptoms, employment and social functioning. Overall, these studies will (1) produce data on the relationship between alcohol consumption, other drug use, HIV risk- taking behaviors, and psychosocial functioning and (2) provide information that can be used by clinicians to treat alcohol dependence and alcohol-related problems among methadone patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT OF ADULT ADHD IN METHADONE PATIENTS Principal Investigator & Institution: Levin, Frances R. Q. J. Kennedy Associate Professor of Cli; New York State Psychiatric Institute 1051 Riverside Dr New York, NY 10032
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Timing: Fiscal Year 2001; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: In spite of the availability of effective pharmacologic agents for the treatment of opiate dependence, such as methadone and naltrexone, successful treatment remains inadequate for many patients. One factor which may contribute to poor treatment outcome for patients in methadone maintenance programs is the presence of comorbid disorders, of which Attention-Deficit Hyperactivity Disorder (ADHD) has been a neglected one. Based on data we have collected, the prevalence of adult ADHD is substantially higher among substance abusers, both methadone-maintained patients and cocaine abusers seeking treatment, compared to the general population. It is our hypothesis that a comorbid diagnosis of ADHD in methadone-maintained patients may impede treatment efficacy. Medications, such as methylphenidate (MPH) and bupropion (BRP), are currently two of the most effective treatments for ADHD. In fact, we have shown that sustained-release MPH is effective in reducing both ADHD symptoms and cocaine use in cocaine abusers with adult ADHD. By treating methadone maintained patients who have adult ADHD with effective medications, we hypothesize that a reduction in ADHD symptoms will improve treatment efficacy as defined by: retention in the treatment study and in the methadone program, reduction in illicit drug use and drug craving, and improvement in functioning based on the Addiction Severity Index and Clinical Global Impression. Specifically, the effectiveness of sustained-release MPH and sustained-release BPR will be assessed using a three-armed, double-blind, placebo-controlled treatment trial in 120 methadone-maintained patients diagnosed with adult ADHD. Unfortunately, ADHD often goes undiagnosed. The second aim of this proposal is to determine the positive predictive value of several self-report instruments used to evaluate adult ADHD. Specifically, we will determine the utility of these instruments for assessing adult ADHD in substance-abusing populations. Overall, this proposal will provide a better understanding of the relationship between ADHD and substance abuse, better diagnostic evaluation, and improved pharmacologic treatment approaches for this sub-population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGY
TREATMENT
RESEARCH
CENTER--BEHAVIORAL
Principal Investigator & Institution: Bigelow, George E. Professor and Director; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 30-JUN-2003 Summary: This is a proposal to renew the ongoing, productive drug abuse Treatment Research Center located in the John Hopkins Behavioral Pharmacology Research Unit. The Center unites a group of innovative and productive drug abuse clinical researchers with complementary interests and approaches who share a commitment to the scientific study of drug abuse as a behavioral pharmacologic disorder. The Center integrates human laboratory research with outpatient clinical trials research. Its clinical research resources training and career development resources, and scientific reputation and productivity are outstanding. The general theme for this renewal period is that of treatment comparisons. Five specific components plus a Core are proposed. A human laboratory component will use a naloxone-precipitated withdrawal model to evaluate medications that may suppress the opioid withdrawal syndrome. A second human laboratory component will evaluate factors that influence the persistence of heroin-self administration during methadone maintenance treatment. A clinical trial component will assess the individual and combined effects of opioid pharmacotherapy dose and
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varied incentive-based behavior therapy "doses" in treating combined opioid and cocaine abuse; this study will help to identify which intensities of psychosocial treatment most sensitively reveal the efficacy of pharmacotherapies. A second clinical trial component will assess whether a specific behavior therapy previously shown to be an effective adjunct to methadone--behaviorally-contingent pharmacotherapy--is also effective as an adjunct to LAAM. The fifth component involves both human laboratory studies and clinical trials: human laboratory studies will compare the withdrawal syndromes following discontinuation of methadone, LAAM and buprenorphine; a clinical trial will compare the efficacies and patient acceptabilities of methadone, LAAM and buprenorphine in detoxification treatment. A Core component provides shared resources for patient recruitment, urinalysis testing, statistical analyses, technical/computer support, psychiatric/behavioral assessment, medical supervision, pharmacy preparations, and office and administrative support. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REDUCTION
TREATMENT/SUBSTANCE
USE
DISORDERS/HIV
RISK
Principal Investigator & Institution: Woody, George E. Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 30-AUG-2008 Summary: (provided by applicant): This new Senior Scientist Award will free-up clinical time at the VA so I can continue my research on treatment outcome studies of persons with substance use disorders. My research career began in 1970 and since that time I have been P.I. on 17 grants and co-investigator on another 20 or more. Over the years my research activities have grown such that they conflict with clinical responsibilities that are necessary to maintain my VA salary, even though 75% of that time is for NIH and VA research. This award will allow me to reduce VA time to 5/8ths and reduce patient care and on-call responsibilities to 6 hours/week. Immediate plans are to continue projects that include 1) the Delaware Valley Node of the Clinical Trials Network (CTN) on which I am P.I. and responsible for 4 protocols: buprenorphine/naloxone for opioid dependent patients aged 14-21, motivational enhancement therapy, motivational incentives, and changes in treatment practices as a result of CTN participation; 2) studies on the long term course of HIV risk behavior among persons in and out of methadone treatment and the effect of methadone on immune function; 3) VA studies of patients who dropped out or were suspended from methadone treatment and of "Seeking Safety", a group therapy for veterans with substance use disorders and PTSD; and 4) studies in St. Petersburg, Russia comparing naltrexone with or without fluoxetine for relapse prevention and HIV risk reduction and of comorbidities between HIV, hepatitis B and C, TB and alcohol and drug dependence. Long term plans are to 1) submit a competing renewal of CTN studies in the Fall of '03; 2) implement a study of depot vs oral naltrexone in St. Petersburg; 3) help investigators in St. Petersburg and Porto Alegre, Brazil develop Centers for HIV prevention, treatment and research; and 4) submit a pilot study of buprenorphine for heroin addiction treatment of HIV+ and HIV- patients in Kiev, Ukraine. This work will be done at the University of Pennsylvania/Philadelphia VAMC Addiction Treatment Research Center, the Treatment Research Institute, and the Penn Center for AIDS Research where I have been an active participant since their beginnings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENTS FOR COMPLEX PATIENTS IN NEW SETTINGS Principal Investigator & Institution: Hall, Sharon M. Professor & Vice Chair; Langley Porter Psychiatric Institute; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 29-SEP-1994; Project End 31-AUG-2004 Summary: (Applicant's Abstract) This is the competing continuation application of the San Francisco Treatment Research Center (TRC). In the last 3-1/2 years, TRC investigators have collaborated productively in science, training, and dissemination. The specific aims of the four currently funded components will be met, and expanded upon. The current application is unified around a theme of behavioral treatments of complex drug abusing patients in new settings. Four scientific components are proposed, supported by two cores. The primary project in each component is a controlled clinical trial of an innovative intervention in a "real-life" setting, with cross-component collaboration in descriptive, pilot, and integrative studies. Each component targets a group of drug abusers with a serious co-occurring disorder. The four components are: (1) a trial of a behavioral skills training intervention to promote reduction in drug use of drug dependent seriously mentally ill patients in clinical case management programs; (2) a trial evaluating the effects of a voucher-based contingency system on drug use and health maintenance behaviors of HIV-positive opioid users in methadone treatment; (3) a trial to evaluate intervention strategies provided in a hospital-based medical emergency department to link opioid users with acute medical problems to methadone treatment; and (4) a trial to evaluate a behavioral intervention for nicotine dependence for smokers with depressive disorders who are patients of a psychiatric outpatient clinic. The scientific and administrative core provides support for training, dissemination, measurement, health economics, and administration, as well as providing an integrating intellectual focus. The biostatistical core provides advanced statistical support, and uses data from the planned components to complete relevant research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TSF TO ENHANCE TREATMENT OF COCAINE DEPENDENCE Principal Investigator & Institution: Carroll, Kathleen;; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: Cocaine use remains epidemic among most methadone maintenance programs and is associated with a host of concurrent problems, particularly higher risk of intravenous drug use and HIV. Disulfiram is a promising treatment for cocaine abuse in this setting, but this effect must be replicated with a larger sample. Moreover, it is critical to evaluate whether disulfiram's effectiveness can be enhanced though adding a more potent psychotherapeutic approach. Manualized Twelve-Step Facilitation (TSF) is a promising but understudied psychotherapeutic approach worthy of extended empirical evaluation. The proposed 2X2 design will permit evaluation of TSF as adjunct to standard methadone maintenance as well as its benefits in combination with disulfiram. In this Stage II study, 180 cocaine-dependent methadone-maintained opioid addicts will be assigned, using urn randomization, to one of four treatments: (1) TwelveStep Facilitation (TSF) in addition to standard methadone counseling plus disulfiram, (2) Twelve-Step Facilitation (TSF) plus placebo, (3) Standard methadone counseling plus disulfiram, or (4) Standard methadone counseling plus placebo. Study treatments will be manual-guided and will last 12 weeks. The primary outcome will be reduction in
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cocaine use, as assessed by self-report and confirmed by thrice-weekly urinalysis. Second outcomes will include reductions in illicit opioid and alcohol use, as well as improvements in psychosocial functioning. Treatments will be delivered by experienced clinicians, who will receive training and ongoing supervision to prevent drift during the course of the study. Supervised urines will be collected thrice weekly. All counseling sessions will be videotaped for ongoing therapist supervision and process assessment. Follow-ups at 1,3, 6, 9 and 12 months after cessation of study treatments will assess the durability and/or delayed emergence of treatment effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “methadone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for methadone in the PubMed Central database: •
Effect of government recommendations on methadone prescribing in south east England: comparison of 1995 and 1997 surveys. by Strang J, Sheridan J. 1998 Nov 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28729
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Effect of national guidelines on prescription of methadone: analysis of NHS prescription data, England 1990-2001. by Strang J, Sheridan J. 2003 Aug 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=169636
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Glucuronidation of 3[prime prime or minute]-Azido-3[prime prime or minute]Deoxythymidine (Zidovudine) by Human Liver Microsomes: Relevance to Clinical Pharmacokinetic Interactions with Atovaquone, Fluconazole, Methadone, and Valproic Acid. by Trapnell CB, Klecker RW, Jamis-Dow C, Collins JM. 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105651
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Methadone maintenance expands inside federal prisons. by Sibbald B. 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=134303
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Nonconventional Opioid Binding Sites Mediate Growth Inhibitory Effects of Methadone on Human Lung Cancer Cells. by Maneckjee R, Minna JD. 1992 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48410
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with methadone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “methadone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for methadone (hyperlinks lead to article summaries): •
A case for addressing cigarette use in methadone and other opioid treatment programs. Author(s): Richter KP, Ahluwalia JS. Source: J Addict Dis. 2000; 19(4): 35-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11110063&dopt=Abstract
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A case of a methadone-induced movement disorder. Author(s): Clark JD, Elliott J. Source: The Clinical Journal of Pain. 2001 December; 17(4): 375-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783819&dopt=Abstract
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A case study of employment case management with chronically unemployed methadone maintained clients. Author(s): Zanis DA, Coviello D. Source: J Psychoactive Drugs. 2001 January-March; 33(1): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11333003&dopt=Abstract
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A cluster of nine overdoses (one fatal) related to methadone in the north of France: a lesson for drug policy in frontier regions. Author(s): Brunelle E, Rotily M. Source: Addiction (Abingdon, England). 2002 September; 97(9): 1221-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199840&dopt=Abstract
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A community-based trial of vocational problem-solving to increase employment among methadone patients. Author(s): Zanis DA, Coviello D, Alterman AI, Appling SE. Source: Journal of Substance Abuse Treatment. 2001 July; 21(1): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516923&dopt=Abstract
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A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence. Author(s): Rawson RA, Huber A, McCann M, Shoptaw S, Farabee D, Reiber C, Ling W. Source: Archives of General Psychiatry. 2002 September; 59(9): 817-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215081&dopt=Abstract
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A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. Author(s): Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE. Source: The New England Journal of Medicine. 2000 November 2; 343(18): 1290-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11058673&dopt=Abstract
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A confidential enquiry into methadone-related deaths. Author(s): Scott RT, Jay MJ, Keith R, Oliver JS, Cassidy MT. Source: Addiction (Abingdon, England). 1999 December; 94(12): 1789-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717957&dopt=Abstract
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A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Author(s): Ling W, Wesson DR, Charuvastra C, Klett CJ. Source: Archives of General Psychiatry. 1996 May; 53(5): 401-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624183&dopt=Abstract
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A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users. Author(s): Batki SL, Gruber VA, Bradley JM, Bradley M, Delucchi K. Source: Drug and Alcohol Dependence. 2002 May 1; 66(3): 283-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062463&dopt=Abstract
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A differential assessment of the cumulative versus stabilizing effect of methadone maintenance treatment. Author(s): Powers KI, Anglin MD. Source: Evaluation Review. 1998 April; 22(2): 175-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10183305&dopt=Abstract
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A discordance between cytochrome P450 2D6 genotype and phenotype in patients undergoing methadone maintenance treatment. Author(s): Shiran MR, Chowdry J, Rostami-Hodjegan A, Ellis SW, Lennard MS, Iqbal MZ, Lagundoye O, Seivewright N, Tucker GT. Source: British Journal of Clinical Pharmacology. 2003 August; 56(2): 220-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895196&dopt=Abstract
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A German model for methadone conversion. Author(s): Nauck F, Ostgathe C, Dickerson ED. Source: Am J Hosp Palliat Care. 2001 May-June; 18(3): 200-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406897&dopt=Abstract
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A mandatory short-term methadone-to-abstinence program in New York City. Author(s): Winick C. Source: The Mount Sinai Journal of Medicine, New York. 2001 January; 68(1): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135505&dopt=Abstract
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A meta-analysis comparing buprenorphine to methadone for treatment of opiate dependence. Author(s): Barnett PG, Rodgers JH, Bloch DA. Source: Addiction (Abingdon, England). 2001 May; 96(5): 683-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331027&dopt=Abstract
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A meta-analysis comparing the effectiveness of buprenorphine and methadone. Author(s): West SL, O'Neal KK, Graham CW. Source: Journal of Substance Abuse. 2000; 12(4): 405-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452842&dopt=Abstract
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A multicenter randomized evaluation of methadone medical maintenance. Author(s): King VL, Stoller KB, Hayes M, Umbricht A, Currens M, Kidorf MS, Carter JA, Schwartz R, Brooner RK. Source: Drug and Alcohol Dependence. 2002 January 1; 65(2): 137-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772475&dopt=Abstract
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A naturalistic study on ending blind dosing in a methadone maintenance clinic in Israel. Author(s): Bleich A, Gelkopf M, Hayward R, Adelson M. Source: Drug and Alcohol Dependence. 2001 January 1; 61(2): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11137284&dopt=Abstract
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A path analysis of cognitive, affective, and behavioral predictors of treatment response in a methadone maintenance program. Author(s): Avants SK, Margolin A, Mckee S. Source: Journal of Substance Abuse. 2000; 11(3): 215-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11026121&dopt=Abstract
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A pilot study comparing severely and persistently mentally ill opiate-addicted patients in dual-diagnosis treatment with patients in methadone maintenance. Author(s): Jaffe C, Comtois KA, Calsyn DA, Saxon AJ. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 1998 Fall; 7(4): 288-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9809133&dopt=Abstract
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A pilot study of a Neuro-Stimulator Device vs. methadone in alleviating opiate withdrawal symptoms. Author(s): Elmoghazy E, Johnson BD, Alling FA. Source: Nida Res Monogr. 1989; 95: 388-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2701306&dopt=Abstract
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A pilot study to determine the usefulness of the urinary excretion of methadone and its primary metabolite (EDDP) as potential markers of compliance in methadone detoxification programs. Author(s): George S, Braithwaite RA. Source: Journal of Analytical Toxicology. 1999 March-April; 23(2): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10192409&dopt=Abstract
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A preliminary, controlled investigation of magnesium L-aspartate hydrochloride for illicit cocaine and opiate use in methadone-maintained patients. Author(s): Margolin A, Kantak K, Copenhaver M, Avants SK. Source: J Addict Dis. 2003; 22(2): 49-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703668&dopt=Abstract
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A prospective clinical audit of methadone maintenance therapy at the Royal Newcastle Hospital. Author(s): Foy A, Drinkwater V, White A. Source: The Medical Journal of Australia. 1989 September 18; 151(6): 332-4, 337. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2593943&dopt=Abstract
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A prospective study of syphilis and HIV infection among injection drug users receiving methadone in the Bronx, NY. Author(s): Gourevitch MN, Hartel D, Schoenbaum EE, Selwyn PA, Davenny K, Friedland GH, Klein RS. Source: American Journal of Public Health. 1996 August; 86(8 Pt 1): 1112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8712270&dopt=Abstract
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A psychoeducational approach to methadone maintenance treatment. Author(s): Stark MJ. Source: Journal of Substance Abuse Treatment. 1989; 6(3): 169-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2795706&dopt=Abstract
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A randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms. Author(s): Dean AJ, Bell J, Mascord DJ, Parker G, Christie MJ. Source: Journal of Affective Disorders. 2002 October; 72(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12204321&dopt=Abstract
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A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients. Author(s): Cornish JW, Herman BH, Ehrman RN, Robbins SJ, Childress AR, Bead V, Esmonde CA, Martz K, Poole S, Caruso FS, O'Brien CP. Source: Drug and Alcohol Dependence. 2002 July 1; 67(2): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095667&dopt=Abstract
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A reduction in HIV positive and an increase in hepatitis C positive subjects in methadone maintenance treatments. Author(s): Ladewig D. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2001 July 14; 131(27-28): 422. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571847&dopt=Abstract
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A review of methadone deaths in Jefferson County, Alabama. Author(s): Mikolaenko I, Robinson CA Jr, Davis GG. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 2002 September; 23(3): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198363&dopt=Abstract
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A risk-benefit analysis of methadone maintenance treatment. Author(s): Bell J, Zador D. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2000 March; 22(3): 179-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10738842&dopt=Abstract
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A schema for evaluating methadone maintenance programs. Author(s): Ball JC. Source: Nida Res Monogr. 1989; 95: 74-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2641057&dopt=Abstract
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A single dose of methadone inhibits cytochrome P-4503A activity in healthy volunteers as assessed by the urinary cortisol ratio. Author(s): Boulton DW, Arnaud P, DeVane CL. Source: British Journal of Clinical Pharmacology. 2001 April; 51(4): 350-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318772&dopt=Abstract
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A staging system to predict prognosis among methadone maintenance patients, based on admission characteristics. Author(s): Favrat B, Rao S, O'Connor PG, Schottenfeld R. Source: Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse. 2002 December; 23(4): 233-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438836&dopt=Abstract
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A study of methadone in fatalities in the Strathclyde Region, 1991-1996. Author(s): Cooper GA, Seymour A, Cassidy MT, Oliver JS. Source: Med Sci Law. 1999 July; 39(3): 233-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466318&dopt=Abstract
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A tale of two policies: the French connection, methadone, and heroin epidemics. Author(s): Agar M, Reisinger HS. Source: Culture, Medicine and Psychiatry. 2002 September; 26(3): 371-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555905&dopt=Abstract
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Absence of opioid withdrawal symptoms in patients receiving methadone and the protease inhibitor lopinavir-ritonavir. Author(s): Clarke S, Mulcahy F, Bergin C, Reynolds H, Boyle N, Barry M, Back DJ. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 April 15; 34(8): 1143-5. Epub 2002 March 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915005&dopt=Abstract
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Abstinence symptomatology associated with cessation of chronic cocaine abuse among methadone-maintained patients. Author(s): Margolin A, Avants SK, Kosten TR. Source: The American Journal of Drug and Alcohol Abuse. 1996 August; 22(3): 377-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8841686&dopt=Abstract
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Abuse liability of flunitrazepam among methadone-maintained patients. Author(s): Farre M, Teran MT, Roset PN, Mas M, Torrens M, Cami J. Source: Psychopharmacology. 1998 December; 140(4): 486-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888625&dopt=Abstract
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Access to narcotic addiction treatment and medical care: prospects for the expansion of methadone maintenance treatment. Author(s): Lewis DC. Source: J Addict Dis. 1999; 18(2): 5-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10334372&dopt=Abstract
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Accidental drug toxicity associated with methadone maintenance treatment. Author(s): Ali RL, Quigley AJ. Source: The Medical Journal of Australia. 1999 February 1; 170(3): 100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10065117&dopt=Abstract
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Active heroin injectors' perceptions and use of methadone maintenance treatment: cynical performance or self-prescribed risk reduction? Author(s): Koester S, Anderson K, Hoffer L. Source: Substance Use & Misuse. 1999 December; 34(14): 2135-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10573308&dopt=Abstract
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Acute physical dependence in man: repeated naloxone-precipitated withdrawal after a single dose of methadone. Author(s): Wright C, Bigelow GE, Stitzer ML. Source: Nida Res Monogr. 1989; 95: 395-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2701308&dopt=Abstract
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Addiction problems and methadone treatment. Author(s): Meulenbeek PA. Source: Journal of Substance Abuse Treatment. 2000 September; 19(2): 171-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10963928&dopt=Abstract
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Additional methadone increases craving for heroin: a double-blind, placebocontrolled study of chronic opiate users receiving methadone substitution treatment. Author(s): Curran HV, Bolton J, Wanigaratne S, Smyth C. Source: Addiction (Abingdon, England). 1999 May; 94(5): 665-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10563031&dopt=Abstract
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Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates. Author(s): Gerra G, Zaimovic A, Raggi MA, Giusti F, Delsignore R, Bertacca S, Brambilla F. Source: Drug and Alcohol Dependence. 2001 December 1; 65(1): 85-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714593&dopt=Abstract
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Alcohol consumption during methadone maintenance treatment. Author(s): Rittmannsberger H, Silberbauer C, Lehner R, Ruschak M. Source: European Addiction Research. 2000 March; 6(1): 2-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10729737&dopt=Abstract
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Alcohol consumption in heroin users, methadone-substituted and codeinesubstituted patients--frequency and correlates of use. Author(s): Backmund M, Schutz CG, Meyer K, Eichenlaub D, Soyka M. Source: European Addiction Research. 2003 January; 9(1): 45-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566797&dopt=Abstract
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Alcohol use by heroin addicts: evidence for an inverse relationship. A study of methadone maintenance and drug-free treatment samples. Author(s): Anglin MD, Almog IJ, Fisher DG, Peters KR. Source: The American Journal of Drug and Alcohol Abuse. 1989; 15(2): 191-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2729226&dopt=Abstract
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Alcohol use in combination with cocaine, heroin and methadone by medical examiner cases. Author(s): Haberman PW, Noble JA, Dufour MC. Source: J Stud Alcohol. 1995 May; 56(3): 344-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7623474&dopt=Abstract
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Altered HPA axis responsivity to metyrapone testing in methadone maintained former heroin addicts with ongoing cocaine addiction. Author(s): Schluger JH, Borg L, Ho A, Kreek MJ. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 May; 24(5): 568-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282257&dopt=Abstract
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Amantadine does not reduce cocaine use or craving in cocaine-dependent methadone maintenance patients. Author(s): Handelsman L, Limpitlaw L, Williams D, Schmeidler J, Paris P, Stimmel B. Source: Drug and Alcohol Dependence. 1995 October; 39(3): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8556965&dopt=Abstract
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An ad libitum schedule for conversion of morphine to methadone in advanced cancer patients: an open uncontrolled prospective study in a Chinese population. Author(s): Tse DM, Sham MM, Ng DK, Ma HM. Source: Palliative Medicine. 2003 March; 17(2): 206-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701853&dopt=Abstract
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An alternative program for methadone maintenance dropouts: description and preliminary data. Author(s): Goldstein MF, Deren S, Beardsley M, Richman BL. Source: The Mount Sinai Journal of Medicine, New York. 2001 January; 68(1): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135504&dopt=Abstract
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An evaluation of breathing nervous regulation of opiate dependent patients during in 6 months' methadone maintenance treatment programme. Author(s): Kolarzyk E, Targosz D, Pach D. Source: Przegl Lek. 2001; 58(4): 250-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450346&dopt=Abstract
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An increase in overdose mortality during the first 2 weeks after entering or reentering methadone treatment in Amsterdam. Author(s): Buster MC, van Brussel GH, van den Brink W. Source: Addiction (Abingdon, England). 2002 August; 97(8): 993-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144602&dopt=Abstract
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An innovative approach to reducing cannabis use in a subset of methadone maintenance clients. Author(s): Calsyn DA, Saxon AJ. Source: Drug and Alcohol Dependence. 1999 January 7; 53(2): 167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080042&dopt=Abstract
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An integration of three approaches to addiction and methadone maintenance treatment: the self-medication hypothesis, the disease model and social criticism. Author(s): Ann Intern Med. 2002 Sep 17;137(6):I42 Source: The Israel Journal of Psychiatry and Related Sciences. 2002; 39(2): 140-51. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12230382
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An investigation of medical examiner cases in which methadone was detected, Harris County, Texas, 1987-1992. Author(s): Barrett DH, Luk AJ, Parrish RG, Jones TS. Source: J Forensic Sci. 1996 May; 41(3): 442-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8656185&dopt=Abstract
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Analysis of behavioral patterns in five cohorts of patients retained in methadone maintenance programs. Author(s): Kott A, Habel E, Nottingham W. Source: The Mount Sinai Journal of Medicine, New York. 2001 January; 68(1): 46-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135506&dopt=Abstract
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Analysis of methadone and its metabolites in meconium by enzyme immunoassay (EMIT) and GC-MS. Author(s): elSohly MA, Feng S, Murphy TP. Source: Journal of Analytical Toxicology. 2001 January-February; 25(1): 40-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215999&dopt=Abstract
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Application and validation of a urinary methadone metabolite (EDDP) immunoassay to monitor methadone compliance. Author(s): George S, Parmar S, Meadway C, Braithwaite RA. Source: Annals of Clinical Biochemistry. 2000 May; 37 ( Pt 3): 350-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817250&dopt=Abstract
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Are supplementary services provided during methadone maintenance really costeffective? Author(s): Kraft MK, Rothbard AB, Hadley TR, McLellan AT, Asch DA. Source: The American Journal of Psychiatry. 1997 September; 154(9): 1214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9286179&dopt=Abstract
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Assessment of object relations and reality testing in methadone patients. Author(s): Rutherford MJ, Cacciola JS, Alterman AI, McKay JR. Source: The American Journal of Psychiatry. 1996 September; 153(9): 1189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8780424&dopt=Abstract
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Association between self-report of cognitive impairment, HIV status, and cocaine use in a sample of cocaine-dependent methadone-maintained patients. Author(s): Avants SK, Margolin A, McMahon TJ, Kosten TR. Source: Addictive Behaviors. 1997 September-October; 22(5): 599-611. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9347062&dopt=Abstract
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Associations between tobacco smoking and illicit drug use among methadonemaintained opiate-dependent individuals. Author(s): Frosch DL, Shoptaw S, Nahom D, Jarvik ME. Source: Experimental and Clinical Psychopharmacology. 2000 February; 8(1): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10743909&dopt=Abstract
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Attachment behavior and its antecedents in offspring born to methadone-maintained women. Author(s): Goodman G, Hans SL, Cox SM. Source: Journal of Clinical Child Psychology. 1999 March; 28(1): 58-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10070607&dopt=Abstract
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Attendance incentives for outpatient treatment: effects in methadone- and nonmethadone-maintained pregnant drug dependent women. Author(s): Svikis DS, Lee JH, Haug NA, Stitzer ML. Source: Drug and Alcohol Dependence. 1997 October 25; 48(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9330919&dopt=Abstract
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Attitudes and beliefs of staff working in methadone maintenance clinics. Author(s): Caplehorn JR, Irwig L, Saunders JB. Source: Substance Use & Misuse. 1996 March; 31(4): 437-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8851811&dopt=Abstract
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Attitudes toward methadone maintenance: implications for HIV prevention. Author(s): Zule WA, Desmond DP. Source: J Psychoactive Drugs. 1998 January-February; 30(1): 89-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9565212&dopt=Abstract
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B vitamins status: effect of prolonged heroin addiction and methadone treatment. Author(s): Prayurahong B, Migasena P, Pongpaew P, Vudhivai N, Busapathumrong P. Source: J Med Assoc Thai. 1991 March; 74(3): 131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1861128&dopt=Abstract
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Basic issues pertaining to the effectiveness of methadone maintenance treatment. Author(s): Ball JC, Corty E. Source: Nida Res Monogr. 1988; 86: 178-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3140030&dopt=Abstract
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Behavior and development patterns in children born to heroin-addicted and methadone-addicted mothers. Author(s): Hayford SM, Epps RP, Dahl-Regis M. Source: Journal of the National Medical Association. 1988 November; 80(11): 1197-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2470912&dopt=Abstract
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Beliefs about methadone in an inner-city methadone clinic. Author(s): Stancliff S, Myers JE, Steiner S, Drucker E. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2002 December; 79(4): 571-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468676&dopt=Abstract
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Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel: characteristics and a pharmacotherapeutic approach. Author(s): Bleich A, Gelkopf M, Weizman T, Adelson M. Source: The Israel Journal of Psychiatry and Related Sciences. 2002; 39(2): 104-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227225&dopt=Abstract
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Benzodiazepine and sedative use/abuse by methadone maintenance clients. Author(s): Iguchi MY, Handelsman L, Bickel WK, Griffiths RR. Source: Drug and Alcohol Dependence. 1993 May; 32(3): 257-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8102331&dopt=Abstract
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Benzodiazepines and other psychotropic drugs abused by patients in a methadone maintenance program: familiarity and preference. Author(s): Barnas C, Rossmann M, Roessler H, Riemer Y, Fleischhacker WW. Source: Journal of Clinical Psychopharmacology. 1992 December; 12(6): 397-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1361936&dopt=Abstract
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Benzodiazepines and other psychotropic drugs abused by patients in a methadone maintenance program: familiarity and preference. Author(s): Barnas C, Rossmann M, Roessler H, Riemer Y, Fleischhacker WW. Source: Clinical Neuropharmacology. 1992; 15 Suppl 1 Pt A: 110A-111A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1354020&dopt=Abstract
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Beta endorphin levels during heroin, methadone, buprenorphine, and naloxone challenges: preliminary findings. Author(s): Kosten TR, Morgan C, Kreek MJ. Source: Biological Psychiatry. 1992 September 15; 32(6): 523-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1445968&dopt=Abstract
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Beta endorphin levels in CSF during methadone maintenance. Author(s): Kosten TR, Kreek MJ, Swift C, Carney MK, Ferdinands L. Source: Life Sciences. 1987 August 31; 41(9): 1071-6. Erratum In: Life Sci 1987 October 5; 41(14): 1761. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2956475&dopt=Abstract
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Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Author(s): Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP. Source: Pharmacogenetics. 1996 October; 6(5): 403-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8946472&dopt=Abstract
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Binding of d-methadone, l-methadone, and dl-methadone to proteins in plasma of healthy volunteers: role of the variants of alpha 1-acid glycoprotein. Author(s): Eap CB, Cuendet C, Baumann P. Source: Clinical Pharmacology and Therapeutics. 1990 March; 47(3): 338-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2311335&dopt=Abstract
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Biological correlates of methadone maintenance pharmacotherapy. Author(s): Kreek MJ. Source: Annales De Medecine Interne. 1994 November; 145 Suppl 3: 9-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7880038&dopt=Abstract
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Biperiden for excessive sweating from methadone. Author(s): Caflisch C, Figner B, Eich D. Source: The American Journal of Psychiatry. 2003 February; 160(2): 386-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562595&dopt=Abstract
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Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs. Author(s): Xiao Y, Smith RD, Caruso FS, Kellar KJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 October; 299(1): 366-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561100&dopt=Abstract
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Bradycardia associated with intravenous methadone administered for sedation in a patient with acute respiratory distress syndrome. Author(s): Karir V. Source: Pharmacotherapy. 2002 September; 22(9): 1196-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222559&dopt=Abstract
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Broad beneficial effects of cocaine abstinence reinforcement among methadone patients. Author(s): Silverman K, Wong CJ, Umbricht-Schneiter A, Montoya ID, Schuster CR, Preston KL. Source: Journal of Consulting and Clinical Psychology. 1998 October; 66(5): 811-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803700&dopt=Abstract
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Bromocriptine treatment of cocaine abuse in patients maintained on methadone. Author(s): Kosten TR, Schumann B, Wright D. Source: The American Journal of Psychiatry. 1988 March; 145(3): 381-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3344859&dopt=Abstract
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Buprenorphine and naloxone interactions in methadone maintenance patients. Author(s): Mendelson J, Jones RT, Welm S, Brown J, Batki SL. Source: Biological Psychiatry. 1997 June 1; 41(11): 1095-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146820&dopt=Abstract
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Buprenorphine effects in methadone-maintained volunteers: effects at two hours after methadone. Author(s): Strain EC, Preston KL, Liebson IA, Bigelow GE. Source: The Journal of Pharmacology and Experimental Therapeutics. 1995 February; 272(2): 628-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7853176&dopt=Abstract
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Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Author(s): Mattick RP, Kimber J, Breen C, Davoli M. Source: Cochrane Database Syst Rev. 2003; (2): Cd002207. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804429&dopt=Abstract
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Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Author(s): Cochrane Database Syst Rev. 2003;(2):CD002209 Source: Cochrane Database Syst Rev. 2002; (4): Cd002207. Review. Update In: /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12804430
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Buprenorphine versus methadone in the treatment of opioid dependence: selfreports, urinalysis, and addiction severity index. Author(s): Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Source: Journal of Clinical Psychopharmacology. 1996 February; 16(1): 58-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8834420&dopt=Abstract
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Buprenorphine versus methadone in the treatment of opioid-dependent cocaine users. Author(s): Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Source: Psychopharmacology. 1994 December; 116(4): 401-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7701040&dopt=Abstract
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Buprenorphine versus methadone maintenance for opioid dependence. Author(s): Kosten TR, Schottenfeld R, Ziedonis D, Falcioni J. Source: The Journal of Nervous and Mental Disease. 1993 June; 181(6): 358-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8501457&dopt=Abstract
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Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Author(s): Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stuhlinger G, Pezawas L, Aschauer HN, Kasper S. Source: Addiction (Abingdon, England). 1999 September; 94(9): 1337-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10615719&dopt=Abstract
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Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients. Author(s): Mattick RP, Ali R, White JM, O'Brien S, Wolk S, Danz C. Source: Addiction (Abingdon, England). 2003 April; 98(4): 441-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653814&dopt=Abstract
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Buprenorphine versus methadone maintenance treatment in an ambulant setting: a health-related quality of life assessment. Author(s): Giacomuzzi SM, Riemer Y, Ertl M, Kemmler G, Rossler H, Hinterhuber H, Kurz M. Source: Addiction (Abingdon, England). 2003 May; 98(5): 693-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751987&dopt=Abstract
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Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Author(s): Schottenfeld RS, Pakes JR, Oliveto A, Ziedonis D, Kosten TR. Source: Archives of General Psychiatry. 1997 August; 54(8): 713-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9283506&dopt=Abstract
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Buprenorphine: an alternative to methadone for heroin dependence treatment. Author(s): Resnick RB, Galanter M, Pycha C, Cohen A, Grandison P, Flood N. Source: Psychopharmacology Bulletin. 1992; 28(1): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1609035&dopt=Abstract
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Buprenorphine: beyond methadone? Author(s): Rosen MI, Kosten TR. Source: Hosp Community Psychiatry. 1991 April; 42(4): 347-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2050347&dopt=Abstract
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Bupropion reduces cocaine abuse in methadone-maintained patients. Author(s): Margolin A, Kosten T, Petrakis I, Avants SK, Kosten T. Source: Archives of General Psychiatry. 1991 January; 48(1): 87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1898631&dopt=Abstract
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Can methadone maintenance for heroin-dependent patients retained in general practice reduce criminal conviction rates and time spent in prison? Author(s): Keen J, Rowse G, Mathers N, Campbell M, Seivewright N. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2000 January; 50(450): 48-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695069&dopt=Abstract
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Can we use methadone for analgesia in neonates? Author(s): Chana SK, Anand KJ. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2001 September; 85(2): F79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11517197&dopt=Abstract
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Canadian illicit opiate users' views on methadone and other opiate prescription treatment: an exploratory qualitative study. Author(s): Fischer B, Chin AT, Kuo I, Kirst M, Vlahov D. Source: Substance Use & Misuse. 2002 March; 37(4): 495-522. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064431&dopt=Abstract
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Cannabis use and treatment outcome in methadone maintenance. Author(s): Nixon LN. Source: Addiction (Abingdon, England). 2003 September; 98(9): 1321-2; Author Reply 1322-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930220&dopt=Abstract
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Causes and rates of death among methadone maintenance patients before and after the onset of the HIV/AIDS epidemic. Author(s): Appel PW, Joseph H, Richman BL. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 444-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064496&dopt=Abstract
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Cerebral phosphorus metabolite abnormalities in opiate-dependent polydrug abusers in methadone maintenance. Author(s): Kaufman MJ, Pollack MH, Villafuerte RA, Kukes TJ, Rose SL, Mendelson JH, Cohen BM, Renshaw PF. Source: Psychiatry Research. 1999 June 30; 90(3): 143-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466733&dopt=Abstract
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Change in drug-using networks of injecting drug users during methadone treatment: a pilot study using snowball recruitment and intensive interviews. Author(s): Willems JC, Iguchi MY, Lidz V, Bux DA Jr. Source: Substance Use & Misuse. 1997 September; 32(11): 1539-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9336864&dopt=Abstract
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Change intolerance to shifts in methadone formulation: a preliminary investigation. Author(s): Silver JS, Shaffer HJ. Source: Journal of Substance Abuse Treatment. 1996 July-August; 13(4): 331-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9076651&dopt=Abstract
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Changes in HIV risk behaviors among cocaine-using methadone patients. Author(s): Magura S, Rosenblum A, Rodriguez EM. Source: J Addict Dis. 1998; 17(4): 71-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9848033&dopt=Abstract
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Changes in methadone treatment practices: results from a national panel study, 19882000. Author(s): D'Aunno T, Pollack HA. Source: Jama : the Journal of the American Medical Association. 2002 August 21; 288(7): 850-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186602&dopt=Abstract
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Changes in methadone treatment practices: results from a panel study, 1988-1995. Author(s): D'Aunno T, Folz-Murphy N, Lin X. Source: The American Journal of Drug and Alcohol Abuse. 1999 November; 25(4): 68199. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548442&dopt=Abstract
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Changes in Millon Clinical Multiaxial Inventory scores among opiate addicts as a function of retention in methadone maintenance treatment and recent drug use. Author(s): Calsyn DA, Wells EA, Fleming C, Saxon AJ. Source: The American Journal of Drug and Alcohol Abuse. 2000 May; 26(2): 297-309. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852362&dopt=Abstract
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Changes in mortality, arrests, and hospitalizations in nonvoluntarily treated heroin addicts in relation to methadone treatment. Author(s): Fugelstad A, Agren G, Romelsjo A. Source: Substance Use & Misuse. 1998 December; 33(14): 2803-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9869445&dopt=Abstract
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Changing patient characteristics with increased methadone maintenance availability. Author(s): Brands B, Blake J, Marsh D. Source: Drug and Alcohol Dependence. 2002 March 1; 66(1): 11-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11850131&dopt=Abstract
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Characteristics of fatal methadone overdose in Manchester, 1985-94. Author(s): Cairns A, Roberts IS, Benbow EW. Source: Bmj (Clinical Research Ed.). 1996 August 3; 313(7052): 264-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8704535&dopt=Abstract
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Characteristics of methadone maintenance patients with chronic pain. Author(s): Jamison RN, Kauffman J, Katz NP. Source: Journal of Pain and Symptom Management. 2000 January; 19(1): 53-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10687327&dopt=Abstract
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Characterization of methadone overdose: clinical considerations and the scientific evidence. Author(s): Wolff K. Source: Therapeutic Drug Monitoring. 2002 August; 24(4): 457-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142628&dopt=Abstract
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Characterization of methadone receptor subtypes present in human brain and lung tissues. Author(s): Maneckjee R, Minna JD. Source: Life Sciences. 1997; 61(22): Pl 333-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9393946&dopt=Abstract
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Characterization of the stereoselective metabolism of methadone and its primary metabolite via cyclodextrin capillary electrophoretic determination of their urinary enantiomers. Author(s): Lanz M, Thormann W. Source: Electrophoresis. 1996 December; 17(12): 1945-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9034780&dopt=Abstract
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Characterizing “nonresponsive” methadone patients. Author(s): Belding MA, McLellan AT, Zanis DA, Incmikoski R. Source: Journal of Substance Abuse Treatment. 1998 November-December; 15(6): 485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9845861&dopt=Abstract
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Childhood abuse as a risk for partner abuse among women in methadone maintenance. Author(s): Gilbert L, el-Bassel N, Schilling RF, Friedman E. Source: The American Journal of Drug and Alcohol Abuse. 1997 November; 23(4): 58195. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366975&dopt=Abstract
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Chlordiazepoxide vs. methadone in opiate withdrawal: a preliminary double blind trial. Author(s): Drummond DC, Turkington D, Rahman MZ, Mullin PJ, Jackson P. Source: Drug and Alcohol Dependence. 1989 January; 23(1): 63-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2646089&dopt=Abstract
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Choreiform movements after a single dose of methadone. Author(s): Lussier D, Cruciani RA. Source: Journal of Pain and Symptom Management. 2003 August; 26(2): 688-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906951&dopt=Abstract
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Clinical applications of methadone. Author(s): Wheeler WL, Dickerson ED. Source: Am J Hosp Palliat Care. 2000 May-June; 17(3): 196-203. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886072&dopt=Abstract
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Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients. Author(s): De Conno F, Groff L, Brunelli C, Zecca E, Ventafridda V, Ripamonti C. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1996 October; 14(10): 2836-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8874346&dopt=Abstract
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Clinical management of methadone dependence during pregnancy. Author(s): Wilbourne P, Wallerstedt C, Dorato V, Curet LB. Source: The Journal of Perinatal & Neonatal Nursing. 2001 March; 14(4): 26-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930521&dopt=Abstract
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Clinical nuances of pediatric methadone intoxication. Author(s): Brooks DE, Roberge RJ, Spear A. Source: Vet Hum Toxicol. 1999 December; 41(6): 388-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10592949&dopt=Abstract
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Clomethiazole treatment of alcohol withdrawal delirium in a patient under methadone maintenance. Author(s): Gross A, Soyka M. Source: Pharmacopsychiatry. 1996 November; 29(6): 229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8956355&dopt=Abstract
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Clonidine use and abuse among methadone program applicants and patients. Author(s): Beuger M, Tommasello A, Schwartz R, Clinton M. Source: Journal of Substance Abuse Treatment. 1998 November-December; 15(6): 589-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9845872&dopt=Abstract
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Closure of an open drug scene--a case register-based analysis of the impact on the demand for methadone maintenance treatment. Author(s): Falcato L, Stohler R, Dursteler-Mac Farland KM, Eichenberger A, Eich D, Rossler W. Source: Addiction (Abingdon, England). 2001 April; 96(4): 623-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300965&dopt=Abstract
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Cocaine and heroin use by methadone maintenance patients. Author(s): Ball JC, Ross A, Jaffe JH. Source: Nida Res Monogr. 1989; 95: 328. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2640981&dopt=Abstract
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Cognitive impairment among methadone maintenance patients. Author(s): Darke S, Sims J, McDonald S, Wickes W. Source: Addiction (Abingdon, England). 2000 May; 95(5): 687-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885043&dopt=Abstract
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Cognitive impairment in methadone maintenance patients. Author(s): Mintzer MZ, Stitzer ML. Source: Drug and Alcohol Dependence. 2002 June 1; 67(1): 41-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062778&dopt=Abstract
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Cognitive-motor performance of methadone-maintained patients. Author(s): Specka M, Finkbeiner T, Lodemann E, Leifert K, Kluwig J, Gastpar M. Source: European Addiction Research. 2000 March; 6(1): 8-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10729738&dopt=Abstract
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Combined use of trazodone-naltrexone versus clonidine-naltrexone in rapid withdrawal from methadone treatment. A comparative inpatient study. Author(s): Pozzi G, Conte G, De Risio S. Source: Drug and Alcohol Dependence. 2000 June 1; 59(3): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812288&dopt=Abstract
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Comment on: Doverty et al, Hyperalgesic responses in methadone maintenance patients (Pain 2001;90;91-6). Author(s): David Clark J. Source: Pain. 2002 October; 99(3): 608-9; Author Repyl 3-609-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406539&dopt=Abstract
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Comparing buprenorphine and methadone maintenance. Author(s): Newman RG. Source: The Journal of Nervous and Mental Disease. 1994 April; 182(4): 245-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10678328&dopt=Abstract
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Comparing opiate users in methadone treatment with untreated opiate users: results of a follow-up study with a Toronto opiate user cohort. Author(s): Fischer B, Gliksman L, Rehm J, Daniel N, Medved W. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1999 September-October; 90(5): 299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10570570&dopt=Abstract
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Comparison of methadone and high dosage buprenorphine users in French care centres. Author(s): Barrau K, Thirion X, Micallef J, Chuniaud-Louche C, Bellemin B, San Marco JL. Source: Addiction (Abingdon, England). 2001 October; 96(10): 1433-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571062&dopt=Abstract
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Comparison of patient self-reports and urinalysis results obtained under naturalistic methadone treatment conditions. Author(s): Chermack ST, Roll J, Reilly M, Davis L, Kilaru U, Grabowski J. Source: Drug and Alcohol Dependence. 2000 April 1; 59(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706974&dopt=Abstract
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Comparison of urinary 5-hydroxytryptophol, breath ethanol, and self-report for detection of recent alcohol use during outpatient treatment: a study on methadone patients. Author(s): Helander A, von Wachenfeldt J, Hiltunen A, Beck O, Liljeberg P, Borg S. Source: Drug and Alcohol Dependence. 1999 August 2; 56(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10462090&dopt=Abstract
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Concordance between urinalysis results and self-reported drug use by applicants for methadone maintenance in Australia. Author(s): Digiusto E, Seres V, Bibby A, Batey R. Source: Addictive Behaviors. 1996 May-June; 21(3): 319-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883483&dopt=Abstract
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Consequences and costs of shutting off methadone. Author(s): Anglin MD, Speckart GR, Booth MW, Ryan TM. Source: Addictive Behaviors. 1989; 14(3): 307-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2787586&dopt=Abstract
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Conservative management with naltrexone of an iatrogenic methadone overdose in an opiate-naive patient. Author(s): Dhopesh V, Yu E, Fudala PJ. Source: Journal of Clinical Psychopharmacology. 2002 April; 22(2): 231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910276&dopt=Abstract
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Contamination of antibiotics resulting in severe pediatric methadone poisoning. Author(s): Lalkin A, Kapur BM, Verjee ZH, Koren G. Source: The Annals of Pharmacotherapy. 1999 March; 33(3): 314-7. Erratum In: Ann Pharmacother 1999 September; 33(9): 1011. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200857&dopt=Abstract
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Contingency contracting and systematic desensitization for heroin addicts in methadone maintenance programs. Author(s): Piane G. Source: J Psychoactive Drugs. 2000 July-September; 32(3): 311-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061683&dopt=Abstract
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Contingency management for tobacco smoking in methadone-maintained opiate addicts. Author(s): Shoptaw S, Jarvik ME, Ling W, Rawson RA. Source: Addictive Behaviors. 1996 May-June; 21(3): 409-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883490&dopt=Abstract
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Contingency management in outpatient methadone treatment: a meta-analysis. Author(s): Griffith JD, Rowan-Szal GA, Roark RR, Simpson DD. Source: Drug and Alcohol Dependence. 2000 February 1; 58(1-2): 55-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669055&dopt=Abstract
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Contingent reinforcement sustains post-detoxification abstinence from multiple drugs: a preliminary study with methadone patients. Author(s): Chutuape MA, Silverman K, Stitzer M. Source: Drug and Alcohol Dependence. 1999 March 1; 54(1): 69-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10101619&dopt=Abstract
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Continued heroin use during methadone treatment: relationships between frequency of use and reasons reported for heroin use. Author(s): Best D, Gossop M, Stewart D, Marsden J, Lehmann P, Strang J. Source: Drug and Alcohol Dependence. 1999 February 1; 53(3): 191-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080044&dopt=Abstract
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Continuous epidural infusion of racemic methadone results in effective postoperative analgesia and low plasma concentrations. Author(s): Prieto-Alvarez P, Tello-Galindo I, Cuenca-Pena J, Rull-Bartomeu M, GomarSancho C. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 January; 49(1): 25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782325&dopt=Abstract
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Continuous intravenous infusion of methadone for control of burn pain. Author(s): Concilus R, Denson DD, Knarr D, Warden G, Raj PP. Source: The Journal of Burn Care & Rehabilitation. 1989 September-October; 10(5): 406-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2793918&dopt=Abstract
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Conversion from intrathecal morphine to oral methadone. Author(s): Gebhardt R, Kinney MA. Source: Regional Anesthesia and Pain Medicine. 2002 May-June; 27(3): 319-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016609&dopt=Abstract
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Coping strategies and continued drug use among methadone maintenance patients. Author(s): Belding MA, Iguchi MY, Lamb RJ, Lakin M, Terry R. Source: Addictive Behaviors. 1996 May-June; 21(3): 389-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883488&dopt=Abstract
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Correlates of enrollment in methadone maintenance treatment programs differ by HIV-serostatus. Author(s): Shah NG, Celentano DD, Vlahov D, Stambolis V, Johnson L, Nelson KE, Strathdee SA. Source: Aids (London, England). 2000 September 8; 14(13): 2035-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997409&dopt=Abstract
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Correlates of intention to use the female condom among women taking methadone. Author(s): el-Bassel N, Krishnan SP, Witte S, Schilling RF, Catan V, Pollin S. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 1998 March-April; 8(2): 112-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9542466&dopt=Abstract
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Correlates of participation in AIDS education and HIV antibody testing by methadone patients. Author(s): Magura S, Grossman JI, Lipton DS, Amann KR, Koger J, Gehan K. Source: Public Health Reports (Washington, D.C. : 1974). 1989 May-June; 104(3): 231-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2498972&dopt=Abstract
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Correlates of retention on the South Australian Methadone Program 1981-91. Author(s): Gaughwin M, Solomon P, Ali R. Source: Aust N Z J Public Health. 1998 December; 22(7): 771-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9889441&dopt=Abstract
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Corticotropin-releasing factor testing reveals a dose-dependent difference in methadone maintained vs control subjects. Author(s): Schluger JH, Bart G, Green M, Ho A, Kreek MJ. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 May; 28(5): 985-94. Epub 2003 March 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700714&dopt=Abstract
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Cost-effectiveness of buprenorphine maintenance versus methadone maintenance. Author(s): French MT. Source: Addiction (Abingdon, England). 2001 October; 96(10): 1515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599513&dopt=Abstract
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Counseling as an intervention for the cocaine-abusing methadone maintenance patient. Author(s): Kletter E. Source: J Psychoactive Drugs. 2003 April-June; 35(2): 271-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924750&dopt=Abstract
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Craving despite extremely high methadone dosage. Author(s): de Vos JW, Ufkes JG, van Brussel GH, van den Brink W. Source: Drug and Alcohol Dependence. 1996 March; 40(3): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8861396&dopt=Abstract
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Craving patterns in methadone maintenance treatment with dextromoramide as adjuvant. Author(s): de Vos JW, Ufkes JG, van den Brink W, van Brussel GH, de Wolff FA. Source: Addictive Behaviors. 1999 September-October; 24(5): 707-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10574310&dopt=Abstract
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Cross-sectional study of immunologic abnormalities in intravenous drug abusers on methadone maintenance in New York City. Author(s): Grieco MH, Reddy MM, Fusillo CA, Sorrell SJ, Buimovici-Klein E, Gindi EJ, Brown DK, Saxinger WC, Weiss SH, Flaster ER. Source: Aids (London, England). 1989 April; 3(4): 235-7. Erratum In: Aids 1989 July; 3(7): Following A100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2500957&dopt=Abstract
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Cyclizine abuse among a group of opiate dependents receiving methadone. Author(s): Ruben SM, McLean PC, Melville J. Source: British Journal of Addiction. 1989 August; 84(8): 929-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2775912&dopt=Abstract
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Cytochrome P450 2D6 genotype and methadone steady-state concentrations. Author(s): Eap CB, Broly F, Mino A, Hammig R, Deglon JJ, Uehlinger C, Meili D, Chevalley AF, Bertschy G, Zullino D, Kosel M, Preisig M, Baumann P. Source: Journal of Clinical Psychopharmacology. 2001 April; 21(2): 229-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270921&dopt=Abstract
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Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses. Author(s): Shinderman M, Maxwell S, Brawand-Amey M, Golay KP, Baumann P, Eap CB. Source: Drug and Alcohol Dependence. 2003 March 1; 69(2): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609702&dopt=Abstract
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Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost. Author(s): Avants SK, Margolin A, Sindelar JL, Rounsaville BJ, Schottenfeld R, Stine S, Cooney NL, Rosenheck RA, Li SH, Kosten TR. Source: The American Journal of Psychiatry. 1999 January; 156(1): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9892294&dopt=Abstract
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Death attributed to methadone. Author(s): Vormfelde SV, Poser W. Source: Pharmacopsychiatry. 2001 November; 34(6): 217-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778141&dopt=Abstract
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Deaths attributable to methadone vs buprenorphine in France. Author(s): Auriacombe M, Franques P, Tignol J. Source: Jama : the Journal of the American Medical Association. 2001 January 3; 285(1): 45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150107&dopt=Abstract
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Deaths from methadone and heroin. Author(s): Marks J. Source: Lancet. 1994 April 16; 343(8903): 976. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7909027&dopt=Abstract
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Deaths in methadone maintenance treatment in New South Wales, Australia 19901995. Author(s): Zador D, Sunjic S. Source: Addiction (Abingdon, England). 2000 January; 95(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10723832&dopt=Abstract
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Deaths related to methadone have doubled in Lothian. Author(s): Greenwood J, Zealley H, Gorman D, Fineron P, Squires T. Source: Bmj (Clinical Research Ed.). 1997 June 14; 314(7096): 1763. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9202522&dopt=Abstract
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Decline in HIV-1 seroprevalence and low seroconversion rate among injecting drug users at a methadone maintenance program in New York City. Author(s): Siddiqui NS, Brown LS Jr, Meyer TJ, Gonzalez V. Source: J Psychoactive Drugs. 1993 July-September; 25(3): 245-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8258762&dopt=Abstract
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Decreased maternal-fetal attachment in methadone-maintained pregnant women: a preliminary study. Author(s): Mikhail MS, Youchah J, DeVore N, Ho GY, Anyaegbunam A. Source: J Assoc Acad Minor Phys. 1995; 6(3): 112-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7663100&dopt=Abstract
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Decreased methadone effect after ritonavir initiation. Author(s): Geletko SM, Erickson AD. Source: Pharmacotherapy. 2000 January; 20(1): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641980&dopt=Abstract
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Demographic, medical history and sexual correlates of HIV seropositive methadone maintained women. Author(s): Ajuluchukwu DC, Brown LS Jr, Crummey FC, Foster KF Sr, Ismail YI, Siddiqui N. Source: J Addict Dis. 1993; 12(4): 105-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8292633&dopt=Abstract
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Dependent opioid users assessed for methadone treatment in Otago: patterns of drug use. Author(s): Dore GM, Hargreaves G, Niven BE. Source: N Z Med J. 1997 May 9; 110(1043): 162-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9196499&dopt=Abstract
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Depression among needle exchange program and methadone maintenance clients. Author(s): Brienza RS, Stein MD, Chen M, Gogineni A, Sobota M, Maksad J, Hu P, Clarke J. Source: Journal of Substance Abuse Treatment. 2000 June; 18(4): 331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812305&dopt=Abstract
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Descriptive analysis of cocaine use of methadone patients. Author(s): Kidorf M, Stitzer ML. Source: Drug and Alcohol Dependence. 1993 May; 32(3): 267-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8102332&dopt=Abstract
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Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. Author(s): Oliveto AH, Feingold A, Schottenfeld R, Jatlow P, Kosten TR. Source: Archives of General Psychiatry. 1999 September; 56(9): 812-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884887&dopt=Abstract
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Desipramine treatment of cocaine abuse in methadone maintenance patients. Author(s): Arndt I, Dorozynsky L, Woody G, McLellan AT, O'Brien CP. Source: Nida Res Monogr. 1989; 95: 322-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2701300&dopt=Abstract
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Desipramine treatment of cocaine dependence in methadone-maintained patients. Author(s): Arndt IO, Dorozynsky L, Woody GE, McLellan AT, O'Brien CP. Source: Archives of General Psychiatry. 1992 November; 49(11): 888-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1444727&dopt=Abstract
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Detected heroin use in an Australian methadone maintenance program. Author(s): Caplehorn JR, Reilly DK, Wodak A. Source: Journal of Substance Abuse Treatment. 1993 November-December; 10(6): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8308940&dopt=Abstract
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Detection of alprazolam in three cases of methadone/benzodiazepine overdose. Author(s): Rogers WO, Hall MA, Brissie RM, Robinson CA. Source: J Forensic Sci. 1997 January; 42(1): 155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8988593&dopt=Abstract
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Detection of drug use in a methadone maintenance clinic: sweat patches versus urine testing. Author(s): Taylor JR, Watson ID, Tames FJ, Lowe D. Source: Addiction (Abingdon, England). 1998 June; 93(6): 847-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744120&dopt=Abstract
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Detection of illicit opioid and cocaine use in methadone maintenance treatment. Author(s): Wasserman DA, Korcha R, Havassy BE, Hall SM. Source: The American Journal of Drug and Alcohol Abuse. 1999 August; 25(3): 561-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473015&dopt=Abstract
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Detection of methadone in human hair by gas chromatography/mass spectrometry. Author(s): Balabanova S, Arnold PJ, Brunner H, Luckow V, Wolf HU. Source: Z Rechtsmed. 1989; 102(8): 495-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2800728&dopt=Abstract
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Detection of methadone, LAAM, and their metabolites by methadone immunoassays. Author(s): Cheever ML, Armendariz GA, Moody DE. Source: Journal of Analytical Toxicology. 1999 October; 23(6): 500-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517557&dopt=Abstract
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Detection of methadone, methadone metabolites, and other illicit drugs of abuse in hair of methadone-treatment subjects. Author(s): Goldberger BA, Darraj AG, Caplan YH, Cone EJ. Source: Journal of Analytical Toxicology. 1998 October; 22(6): 526-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9788529&dopt=Abstract
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Detection of opiate use in a methadone maintenance treatment population with the CEDIA 6-acetylmorphine and CEDIA DAU opiate assays. Author(s): Spanbauer AC, Casseday S, Davoudzadeh D, Preston KL, Huestis MA. Source: Journal of Analytical Toxicology. 2001 October; 25(7): 515-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599593&dopt=Abstract
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Determination and pharmacokinetics of dextromoramide in methadone maintenance therapy. Author(s): Ufkes JG, de Vos JW, van Brussel GH. Source: Pharmacy World & Science : Pws. 1998 April; 20(2): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9584342&dopt=Abstract
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Determination of methadone and its metabolites EDDP and EMDP in human hair by headspace solid-phase microextraction and gas chromatography-mass spectrometry. Author(s): Sporkert F, Pragst F. Source: J Chromatogr B Biomed Sci Appl. 2000 September 15; 746(2): 255-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076079&dopt=Abstract
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Determination of methadone and its N-demethylation metabolites in biological specimens by GC-PICI-MS. Author(s): Alburges ME, Huang W, Foltz RL, Moody DE. Source: Journal of Analytical Toxicology. 1996 October; 20(6): 362-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8889671&dopt=Abstract
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Determination of methadone and its primary metabolite in human urine by capillary electrophoretic techniques. Author(s): Molteni S, Caslavska J, Allemann D, Thormann W, Alleman D [corrected to Allemann D. Source: Journal of Chromatography. B, Biomedical Applications. 1994 August 19; 658(2): 355-67. Erratum In: J Chromatogr B Biomed Appl 1994 November 18; 661(2): 367. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7820264&dopt=Abstract
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Determination of methadone in human hair by radioimmunoassay. Author(s): Balabanova S, Wolf HU. Source: Z Rechtsmed. 1989; 102(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2922954&dopt=Abstract
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Determination of methadone in urine using ion trap GC/MS in positive ion chemical ionization mode. Author(s): Moore C, Guzaldo F, Hussain MJ, Lewis D. Source: Forensic Science International. 2001 June 15; 119(2): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376981&dopt=Abstract
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Determination of midazolam and 1'-hydroxymidazolam by liquid chromatographymass spectrometry in plasma of patients undergoing methadone maintenance treatment. Author(s): Shiran MR, Gregory A, Rostami-Hodjegan A, Tucker GT, Lennard MS. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 January 5; 783(1): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450551&dopt=Abstract
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Detoxification from methadone maintenance treatment in Sweden: long-term outcome and effects on quality of life and life situation. Author(s): Eklund C, Melin L, Hiltunen A, Borg S. Source: Int J Addict. 1994 April; 29(5): 627-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8034376&dopt=Abstract
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Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone. Author(s): Seifert J, Metzner C, Paetzold W, Borsutzky M, Passie T, Rollnik J, Wiese B, Emrich HM, Schneider U. Source: Pharmacopsychiatry. 2002 September; 35(5): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237786&dopt=Abstract
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Developing a quality of care index for outpatient methadone treatment programmes. Author(s): Oyefeso A, Clancy C, Ghodse H. Source: Journal of Evaluation in Clinical Practice. 1998 February; 4(1): 39-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9524911&dopt=Abstract
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Development after prenatal exposure to cocaine, heroin and methadone. Author(s): van Baar AL, Soepatmi S, Gunning WB, Akkerhuis GW. Source: Acta Paediatr Suppl. 1994 November; 404: 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7531042&dopt=Abstract
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Development and application of a chiral high performance liquid chromatography assay for pharmacokinetic studies of methadone. Author(s): Boulton DW, Devane CL. Source: Chirality. 2000 October; 12(9): 681-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984743&dopt=Abstract
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Development and psychometric properties of the Verona Service Satisfaction Scale for methadone-treated opioid-dependent patients (VSSS-MT). Author(s): de los Cobos J, Valero S, Haro G, Fidel G, Escuder G, Trujols J, Valderrama JC. Source: Drug and Alcohol Dependence. 2002 October 1; 68(2): 209-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234650&dopt=Abstract
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Development of a transdermal patch of methadone: in vitro evaluation across hairless mouse and human cadaver skin. Author(s): Ghosh TK, Bagherian A. Source: Pharmaceutical Development and Technology. 1996 October; 1(3): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9552311&dopt=Abstract
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Development of validated stereoselective methods for methadone determination in clinical samples. Author(s): Rudaz S, Ortelli D, Gex-Fabry M, Deglon JJ, Balant L, Veuthey JL. Source: Chirality. 1999; 11(5-6): 487-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10419284&dopt=Abstract
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Developmental consequences of prenatal exposure to methadone. Author(s): Hans SL. Source: Annals of the New York Academy of Sciences. 1989; 562: 195-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2742277&dopt=Abstract
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Developmental outcomes of children of mothers dependent on heroin or heroin/methadone during pregnancy. Author(s): Soepatmi S. Source: Acta Paediatr Suppl. 1994 November; 404: 36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7531041&dopt=Abstract
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Diclofenac does not modify methadone bioavailability in cancer patients. Author(s): Bianchi M, Clavenna A, Groff L, Zecca E, Ripamonti C. Source: Journal of Pain and Symptom Management. 1999 April; 17(4): 227-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203873&dopt=Abstract
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Differences in the ratios of morphine to methadone in patients with neuropathic pain versus non-neuropathic pain. Author(s): Gagnon B, Bruera E. Source: Journal of Pain and Symptom Management. 1999 August; 18(2): 120-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10484859&dopt=Abstract
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Differences in the Symptom Check List-90 profiles of black and white methadone patients. Author(s): Platt JJ, Steer RA, Ranieri WF, Metzger DS. Source: Journal of Clinical Psychology. 1989 March; 45(2): 342-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2723093&dopt=Abstract
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Different patterns of sexual dysfunctions associated with psychiatric disorders and psychopharmacological treatment. Results of an investigation by semistructured interview of schizophrenic and neurotic patients and methadone-substituted opiate addicts. Author(s): Teusch L, Scherbaum N, Bohme H, Bender S, Eschmann-Mehl G, Gastpar M. Source: Pharmacopsychiatry. 1995 May; 28(3): 84-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7568370&dopt=Abstract
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Differentiation in the Amsterdam methadone dispensing circuit: determinants of methadone dosage and site of methadone prescription. Author(s): Langendam MW, van Haastrecht HJ, van Brussel GH, Reurs H, van den Hoek AA, Coutinho RA, van Ameijden EJ. Source: Addiction (Abingdon, England). 1998 January; 93(1): 61-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624712&dopt=Abstract
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Dihydrocodeine: a useful tool in the detoxification of methadone-maintained patients. Author(s): Banbery J, Wolff K, Raistrick D. Source: Journal of Substance Abuse Treatment. 2000 October; 19(3): 301-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11027902&dopt=Abstract
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Diminished illicit drug use as a consequence of long-term methadone maintenance. Author(s): Gottheil E, Sterling RC, Weinstein SP. Source: J Addict Dis. 1993; 12(4): 45-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8292639&dopt=Abstract
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Directly observed treatment for tuberculosis. Could be provided by community pharmacists supervising consumption of methadone. Author(s): Sell L, Finch E, Farrell M, Sheridan J, Strang J. Source: Bmj (Clinical Research Ed.). 1996 July 6; 313(7048): 45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8664783&dopt=Abstract
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Disciplining addictions: the bio-politics of methadone and heroin in the United States. Author(s): Bourgois P. Source: Culture, Medicine and Psychiatry. 2000 June; 24(2): 165-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885786&dopt=Abstract
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Disopyramide cross-reactivity in a commercial immunoassay reagent for methadone. Author(s): Moorman P, McCoy M, Hague B, Huge D. Source: Journal of Analytical Toxicology. 1999 July-August; 23(4): 299-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10445496&dopt=Abstract
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Disposition of nasal, intravenous, and oral methadone in healthy volunteers. Author(s): Dale O, Hoffer C, Sheffels P, Kharasch ED. Source: Clinical Pharmacology and Therapeutics. 2002 November; 72(5): 536-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426517&dopt=Abstract
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Distinctive features of the methadone treatment program of Victoria, Australia. Author(s): Harrison S. Source: Addiction (Abingdon, England). 1994 January; 89(1): 95-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8148750&dopt=Abstract
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Distribution of R- and S-methadone into human milk during multiple, medium to high oral dosing. Author(s): Begg EJ, Malpas TJ, Hackett LP, Ilett KF. Source: British Journal of Clinical Pharmacology. 2001 December; 52(6): 681-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11736879&dopt=Abstract
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Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Author(s): Petrakis IL, Carroll KM, Nich C, Gordon LT, McCance-Katz EF, Frankforter T, Rounsaville BJ. Source: Addiction (Abingdon, England). 2000 February; 95(2): 219-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10723850&dopt=Abstract
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Do methadone patients substitute other drugs for heroin? Predicting substance use at 1-year follow-up. Author(s): Fairbank JA, Dunteman GH, Condelli WS. Source: The American Journal of Drug and Alcohol Abuse. 1993; 19(4): 465-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8273767&dopt=Abstract
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Does HIV test result influence methadone maintenance treatment retention? Author(s): Wimbush J, Amicarelli A, Stein MD. Source: Journal of Substance Abuse. 1996; 8(2): 263-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8880665&dopt=Abstract
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Does intravenous methadone provide longer lasting analgesia than intravenous morphine? A randomized, double-blind study. Author(s): Grochow L, Sheidler V, Grossman S, Green L, Enterline J. Source: Pain. 1989 August; 38(2): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2488674&dopt=Abstract
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Does methadone maintenance treatment based on the new national guidelines work in a primary care setting? Author(s): Keen J, Oliver P, Rowse G, Mathers N. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2003 June; 53(491): 461-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939891&dopt=Abstract
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Dose dependent effects of yohimbine on methadone maintained patients. Author(s): Hameedi FA, Woods SW, Rosen MI, Pearsall HR, Kosten TR. Source: The American Journal of Drug and Alcohol Abuse. 1997 May; 23(2): 327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9143642&dopt=Abstract
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Dose ratio between morphine and methadone in patients with cancer pain: a retrospective study. Author(s): Lawlor PG, Turner KS, Hanson J, Bruera ED. Source: Cancer. 1998 March 15; 82(6): 1167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9506365&dopt=Abstract
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Dose-effect relationship between overdose mortality and prescribed methadone dosage in low-threshold maintenance programs. Author(s): van Ameijden EJ, Langendam MW, Coutinho RA. Source: Addictive Behaviors. 1999 July-August; 24(4): 559-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466851&dopt=Abstract
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Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Author(s): Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS. Source: Pharmacotherapy. 2003 June; 23(6): 802-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820821&dopt=Abstract
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Dose-response effects of methadone in the treatment of opioid dependence. Author(s): Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Source: Annals of Internal Medicine. 1993 July 1; 119(1): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8498759&dopt=Abstract
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Double-blind randomized trial of buprenorphine and methadone in opiate dependence. Author(s): Petitjean S, Stohler R, Deglon JJ, Livoti S, Waldvogel D, Uehlinger C, Ladewig D. Source: Drug and Alcohol Dependence. 2001 March 1; 62(1): 97-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173173&dopt=Abstract
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Drug abuse, methadone treatment, and health services use among injection drug users with AIDS. Author(s): Sambamoorthi U, Warner LA, Crystal S, Walkup J. Source: Drug and Alcohol Dependence. 2000 July 1; 60(1): 77-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821992&dopt=Abstract
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Drug use and injection risk-taking among prison methadone maintenance patients. Author(s): Darke S, Kaye S, Finlay-Jones R. Source: Addiction (Abingdon, England). 1998 August; 93(8): 1169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9813898&dopt=Abstract
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Drug use in prison. Methadone maintenance in prison needs to be evaluated. Author(s): Gore SM, Seaman S. Source: Bmj (Clinical Research Ed.). 1996 August 17; 313(7054): 429. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8761258&dopt=Abstract
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Drug use, HIV risk-taking and psychosocial correlates of benzodiazepine use among methadone maintenance clients. Author(s): Drake S, Swift W, Hall W, Ross M. Source: Drug and Alcohol Dependence. 1993 December; 34(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7909749&dopt=Abstract
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Drug use, HIV-related risk behaviors and dropout status of new admissions and readmissions to methadone treatment. Author(s): Deren S, Goldstein MF, Des Jarlais DC, Richman BL, Kang S, Flom PL. Source: Journal of Substance Abuse Treatment. 2001 March; 20(2): 185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306221&dopt=Abstract
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Edinburgh's community drug problem service--a pilot evaluation of methadone substitution. Author(s): Chalmers JW. Source: Health Bull (Edinb). 1990 March; 48(2): 62-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2332336&dopt=Abstract
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Efavirenz decreases methadone blood concentrations. Author(s): Marzolini C, Troillet N, Telenti A, Baumann P, Decosterd LA, Eap CB. Source: Aids (London, England). 2000 June 16; 14(9): 1291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10894303&dopt=Abstract
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Effect of government recommendations on methadone prescribing in South East England: comparison of 1995 and 1997 surveys. Author(s): Strang J, Sheridan J. Source: Bmj (Clinical Research Ed.). 1998 November 28; 317(7171): 1489-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9831575&dopt=Abstract
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Effect of methadone on the biophysical profile. Author(s): Cejtin HE, Mills A, Swift EL. Source: J Reprod Med. 1996 November; 41(11): 819-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8951131&dopt=Abstract
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Effect of national guidelines on prescription of methadone: analysis of NHS prescription data, England 1990-2001. Author(s): Strang J, Sheridan J. Source: Bmj (Clinical Research Ed.). 2003 August 9; 327(7410): 321-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907486&dopt=Abstract
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Effect of ritonavir/saquinavir on stereoselective pharmacokinetics of methadone: results of AIDS Clinical Trials Group (ACTG) 401. Author(s): Gerber JG, Rosenkranz S, Segal Y, Aberg J, D'Amico R, Mildvan D, Gulick R, Hughes V, Flexner C, Aweeka F, Hsu A, Gal J; ACTG 401 Study Team. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2001 June 1; 27(2): 153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11404537&dopt=Abstract
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Effectiveness of a specialized intervention for women in a methadone program. Author(s): Bartholomew NG, Rowan-Szal GA, Chatham LR, Simpson DD. Source: J Psychoactive Drugs. 1994 July-September; 26(3): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7844654&dopt=Abstract
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Effectiveness of methadone maintenance for heroin addiction. Author(s): Murray JB. Source: Psychological Reports. 1998 August; 83(1): 295-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9775685&dopt=Abstract
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Effectiveness of methadone treatment in reducing HIV risk behavior and HIV seroconversion among injecting drug users. Author(s): Gibson DR, Flynn NM, McCarthy JJ. Source: Aids (London, England). 1999 October 1; 13(14): 1807-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10513638&dopt=Abstract
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Effectiveness of streamlined admissions to methadone treatment: a simplified timeseries analysis. Author(s): Dennis ML, Ingram PW, Burks ME, Rachal JV. Source: J Psychoactive Drugs. 1994 April-June; 26(2): 207-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7931865&dopt=Abstract
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Effects of “binge” use of intravenous cocaine in methadone-maintained individuals. Author(s): Foltin RW, Fischman MW. Source: Addiction (Abingdon, England). 1998 June; 93(6): 825-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744118&dopt=Abstract
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Effects of bombesin on methadone-induced apoptosis of human lung cancer cells. Author(s): Heusch WL, Maneckjee R. Source: Cancer Letters. 1999 March 1; 136(2): 177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10355747&dopt=Abstract
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Effects of buprenorphine and methadone in methadone-maintained subjects. Author(s): Walsh SL, June HL, Schuh KJ, Preston KL, Bigelow GE, Stitzer ML. Source: Psychopharmacology. 1995 June; 119(3): 268-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7675960&dopt=Abstract
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Effects of chronic treatment with methadone and naltrexone on sleep in addicts. Author(s): Staedt J, Wassmuth F, Stoppe G, Hajak G, Rodenbeck A, Poser W, Ruther E. Source: European Archives of Psychiatry and Clinical Neuroscience. 1996; 246(6): 305-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8908412&dopt=Abstract
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Effects of HIV triple therapy on methadone levels. Author(s): Akerele EO, Levin F, Nunes E, Brady R, Kleber H. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2002 Fall; 11(4): 308-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584873&dopt=Abstract
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Effects of intravenous methylnaltrexone on opioid-induced gut motility and transit time changes in subjects receiving chronic methadone therapy: a pilot study. Author(s): Yuan CS, Foss JF, O'Connor M, Osinski J, Roizen MF, Moss J. Source: Pain. 1999 December; 83(3): 631-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10568873&dopt=Abstract
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Effects of LAAM and methadone utilization in an opiate agonist treatment program. Author(s): Valdivia JF, Khattak S. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 398-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064490&dopt=Abstract
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Effects of methadone on cognition, mood and craving in detoxifying opiate addicts: a dose-response study. Author(s): Curran HV, Kleckham J, Bearn J, Strang J, Wanigaratne S. Source: Psychopharmacology. 2001 March 1; 154(2): 153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314677&dopt=Abstract
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Effects of methadone or buprenorphine maintenance on the subjective and reinforcing effects of intravenous cocaine in humans. Author(s): Foltin RW, Fischman MW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1996 September; 278(3): 1153-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8819498&dopt=Abstract
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Effects of methadone use during pregnancy on human placental opioid receptors. Author(s): Ahmed MS, Cemerikic B, Mou S, Agbas A. Source: Membr Biochem. 1993 April-June; 10(2): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8395641&dopt=Abstract
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Effects of nicotine on methadone self-administration in humans. Author(s): Spiga R, Schmitz J, Day J 2nd. Source: Drug and Alcohol Dependence. 1998 April 1; 50(2): 157-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9649967&dopt=Abstract
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Effects of prenatal methadone exposure on sex-dimorphic behavior in early schoolage children. Author(s): Sandberg DE, Meyer-Bahlburg HF, Rosen TS, Johnson HL. Source: Psychoneuroendocrinology. 1990; 15(1): 77-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2367618&dopt=Abstract
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Effects of single and multiple intravenous cocaine injections in humans maintained on methadone. Author(s): Foltin RW, Christiansen I, Levin FR, Fischman MW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1995 October; 275(1): 38-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7562574&dopt=Abstract
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Effects of urine testing frequency on outcome in a methadone take-home contingency program. Author(s): Chutuape MA, Silverman K, Stitzer ML. Source: Drug and Alcohol Dependence. 2001 March 1; 62(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173169&dopt=Abstract
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Efficacy of clonidine, guanfacine and methadone in the rapid detoxification of heroin addicts: a controlled clinical trial. Author(s): San L, Cami J, Peri JM, Mata R, Porta M. Source: British Journal of Addiction. 1990 January; 85(1): 141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1968773&dopt=Abstract
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Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients. Author(s): San L, Fernandez T, Cami J, Gossop M. Source: Journal of Substance Abuse Treatment. 1994 September-October; 11(5): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7869468&dopt=Abstract
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Emergency therapeutical approach simulating ultrarapid opioid detoxification in methadone withdrawal precipitated by erroneous administration of naltrexone. Author(s): De Giacomo M, Gaspari R, Stefanelli A, Barelli A, Mannelli P. Source: European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. 1999 June; 6(2): 153-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10461561&dopt=Abstract
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Enantioselective analysis of methadone in saliva by liquid chromatography-mass spectrometry. Author(s): Ortelli D, Rudaz S, Chevalley AF, Mino A, Deglon JJ, Balant L, Veuthey JL. Source: J Chromatogr A. 2000 February 25; 871(1-2): 163-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735296&dopt=Abstract
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Enantioselective analysis of methadone in sweat as monitored by liquid chromatography/ion spray-mass spectrometry. Author(s): Kintz P, Tracqui A, Marzullo C, Darreye A, Tremeau F, Greth P, Ludes B. Source: Therapeutic Drug Monitoring. 1998 February; 20(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9485552&dopt=Abstract
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Enantioselective determination of methadone and its main metabolite 2-ethylidene1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in serum, urine and hair by capillary electrophoresis. Author(s): Frost M, Kohler H, Blaschke G. Source: Electrophoresis. 1997 June; 18(6): 1026-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9221894&dopt=Abstract
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Enantioselective high-performance liquid chromatographic method for the determination of methadone and its main metabolite in urine using an AGP and a C8 column coupled serially. Author(s): Angelo HR, Beck N, Kristensen K. Source: J Chromatogr B Biomed Sci Appl. 1999 March 5; 724(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10202955&dopt=Abstract
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Enantioselective high-performance liquid chromatographic method for the determination of methadone in serum using an AGP and a CN column as chiral and analytical column, respectively. Author(s): Kristensen K, Angelo HR, Blemmer T. Source: J Chromatogr A. 1994 April 22; 666(1-2): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8205236&dopt=Abstract
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Enantioselective high-performance liquid chromatography determination of methadone enantiomers and its major metabolite in human biological fluids using a new derivatized cyclodextrin-bonded phase. Author(s): Pham-Huy C, Chikhi-Chorfi N, Galons H, Sadeg N, Laqueille X, Aymard N, Massicot F, Warnet JM, Claude JR. Source: J Chromatogr B Biomed Sci Appl. 1997 October 24; 700(1-2): 155-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9390725&dopt=Abstract
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Enantioselective separation of methadone and its main metabolite in human hair by liquid chromatography/ion spray-mass spectrometry. Author(s): Kintz P, Eser HP, Tracqui A, Moeller M, Cirimele V, Mangin P. Source: J Forensic Sci. 1997 March; 42(2): 291-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9068189&dopt=Abstract
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Enhanced treatment outcomes for cocaine-using methadone patients. Author(s): Rosenblum A, Magura S, Palij M, Foote J, Handelsman L, Stimmel B. Source: Drug and Alcohol Dependence. 1999 May 3; 54(3): 207-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10372794&dopt=Abstract
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Enhancement of cocaine's abuse liability in methadone maintenance patients. Author(s): Preston KL, Sullivan JT, Strain EC, Bigelow GE. Source: Psychopharmacology. 1996 January; 123(1): 15-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8741950&dopt=Abstract
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Enhancing the effectiveness of methadone using psychotherapeutic interventions. Author(s): O'Brien CP, Woody GE, McLellan AT. Source: Nida Res Monogr. 1995; 150: 5-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8742769&dopt=Abstract
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Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Author(s): Lugo RA, MacLaren R, Cash J, Pribble CG, Vernon DD. Source: Pharmacotherapy. 2001 December; 21(12): 1566-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11765307&dopt=Abstract
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Epidemiological study on the follow-up of patients on methadone prescriptions in France. Working Group of the National Commission for Substitute Treatments. Author(s): Facy F. Source: European Addiction Research. 1999 June; 5(2): 88-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394039&dopt=Abstract
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Epidural methadone for analgesic management of patients with conservatively treated proximal femoral fractures. Author(s): Nyska M, Shapira Y, Klin B, Drenger B, Margulies JY. Source: Journal of the American Geriatrics Society. 1989 October; 37(10): 980-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2794322&dopt=Abstract
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Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: comparison of two clinical experiences. Author(s): Ripamonti C, De Conno F, Groff L, Belzile M, Pereira J, Hanson J, Bruera E. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1998 January; 9(1): 79-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9541687&dopt=Abstract
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Establishing a methadone quality assurance system: rationale and objectives. Author(s): Cooper JR. Source: Nida Res Monogr. 1991; 106: 358-64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1922297&dopt=Abstract
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Estimation of methadone clearance: application in the management of cancer pain. Author(s): Plummer JL, Gourlay GK, Cherry DA, Cousins MJ. Source: Pain. 1988 June; 33(3): 313-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3419839&dopt=Abstract
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Ethnic differences in HIV risk behaviors, self-perceptions, and treatment outcomes among women in methadone maintenance treatment. Author(s): Grella CE, Annon JJ, Anglin MD. Source: J Psychoactive Drugs. 1995 October-December; 27(4): 421-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8788697&dopt=Abstract
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Ethnic differences in narcotics addiction. I. Characteristics of Chicano and Anglo methadone maintenance clients. Author(s): Anglin MD, Ryan TM, Booth MW, Hser YI. Source: Int J Addict. 1988 February; 23(2): 125-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3284826&dopt=Abstract
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Ethnic matching of caseworker and patient in methadone maintenance. Author(s): Maddux JF, Desmond DP. Source: Journal of Substance Abuse Treatment. 1996 May-June; 13(3): 233-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9017566&dopt=Abstract
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Evaluation of in-jail methadone maintenance: preliminary results. Author(s): Magura S, Rosenblum A, Joseph H. Source: Nida Res Monogr. 1992; 118: 192-210. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1620218&dopt=Abstract
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Evaluation of the TDx and ADx methadone immunoassays. Author(s): Caplan YH, Levine B. Source: Clinical Chemistry. 1989 August; 35(8): 1794. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2758657&dopt=Abstract
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Evaluation of the transdermal route for administration of narcotic analgesics: human skin permeability studies of methadone and pethidine. Author(s): Fullerton A, Christrup L, Bundgaard H. Source: Acta Pharm Nord. 1991; 3(3): 181-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1793513&dopt=Abstract
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Evidence for altered desipramine disposition in methadone-maintained patients treated for cocaine abuse. Author(s): Kosten TR, Gawin FH, Morgan C, Nelson JC, Jatlow P. Source: The American Journal of Drug and Alcohol Abuse. 1990; 16(3-4): 329-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2288330&dopt=Abstract
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Excessive alcohol consumption and drinking expectations among clients in methadone maintenance. Author(s): Hillebrand J, Marsden J, Finch E, Strang J. Source: Journal of Substance Abuse Treatment. 2001 October; 21(3): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728789&dopt=Abstract
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Excessive urinary excretion of zinc in drug addicts: a preliminary study during methadone detoxification. Author(s): Iyengar V, Chou PP, Costantino AG, Cook CB. Source: J Trace Elem Electrolytes Health Dis. 1994 December; 8(3-4): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7599515&dopt=Abstract
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Exposure to methadone programs and heroin use. Author(s): Condelli WS, Dunteman GH. Source: The American Journal of Drug and Alcohol Abuse. 1993; 19(1): 65-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8438832&dopt=Abstract
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Extradural bupivacaine and methadone for extracorporal shock-wave lithotripsy. Author(s): Lim M. Source: British Journal of Anaesthesia. 1989 May; 62(5): 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2730834&dopt=Abstract
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Extradural bupivacaine and methadone for extracorporeal shock-wave lithotripsy. Author(s): Drenger B, Shir Y, Pode D, Shapiro A, Magora F, Davidson JT. Source: British Journal of Anaesthesia. 1989 January; 62(1): 82-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2917115&dopt=Abstract
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Extradural methadone and bupivacaine in labour. Author(s): Martin CS, McGrady EM, Colquhoun A, Thorburn J. Source: British Journal of Anaesthesia. 1990 September; 65(3): 330-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2223361&dopt=Abstract
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Factor structure of psychopathy among methadone maintenance patients. Author(s): Darke S, Kaye S, Finlay-Jones R, Hall W. Source: Journal of Personality Disorders. 1998 Summer; 12(2): 162-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9661102&dopt=Abstract
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Factors associated with client-reported HIV infection among clients entering methadone treatment. Author(s): MacGowan RJ, Fichtner RR, Swanson N, Collier C, Kroliczak A, Cole G. Source: Aids Education and Prevention : Official Publication of the International Society for Aids Education. 1997 June; 9(3): 205-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9241388&dopt=Abstract
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Factors associated with employment among methadone patients. Author(s): Zanis DA, Metzger DS, McLellan AT. Source: Journal of Substance Abuse Treatment. 1994 September-October; 11(5): 443-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7869465&dopt=Abstract
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Factors associated with lapses to heroin use during methadone maintenance. Author(s): Wasserman DA, Weinstein MG, Havassy BE, Hall SM. Source: Drug and Alcohol Dependence. 1998 November 1; 52(3): 183-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839144&dopt=Abstract
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Factors associated with successful withdrawal from methadone maintenance treatment in Sweden. Author(s): Eklund C, Hiltunen AJ, Melin L, Borg S. Source: Int J Addict. 1995 August; 30(10): 1335-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7591348&dopt=Abstract
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False-positive immunochemical screen for methadone attributable to metabolites of verapamil. Author(s): Lichtenwalner MR, Mencken T, Tully R, Petosa M. Source: Clinical Chemistry. 1998 May; 44(5): 1039-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9590378&dopt=Abstract
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Fatal methadone and heroin overdoses: time trends in England and Wales. Author(s): Neeleman J, Farrell M. Source: Journal of Epidemiology and Community Health. 1997 August; 51(4): 435-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9328553&dopt=Abstract
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Fatal methadone overdose. Author(s): Hendra TJ, Gerrish SP, Forrest AR. Source: Bmj (Clinical Research Ed.). 1996 August 24; 313(7055): 481-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8776322&dopt=Abstract
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Fatal methadone overdose. Author(s): Benbow EW, Roberts IS, Cairns A. Source: Bmj (Clinical Research Ed.). 1997 March 29; 314(7085): 975. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9099130&dopt=Abstract
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Fatal methadone overdose. Better understanding of body's handling of methadone is needed. Author(s): Benbow EW, Roberts IS, Cairns A. Source: Bmj (Clinical Research Ed.). 1996 December 7; 313(7070): 1479; Author Reply 1480. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8973246&dopt=Abstract
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Fatal methadone overdose. Close observation in intensive care unit is required when naloxone infusion ends. Author(s): Finfer S. Source: Bmj (Clinical Research Ed.). 1996 December 7; 313(7070): 1480. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8973249&dopt=Abstract
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Fatal methadone overdose. Drug services in Manchester were unfairly accused. Author(s): Carnwath T. Source: Bmj (Clinical Research Ed.). 1997 July 5; 315(7099): 55; Author Reply 56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9233335&dopt=Abstract
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Fatal methadone overdose. Naloxone infusion should have been started earlier. Author(s): Nichol N, Pieterse L, Beattie T. Source: Bmj (Clinical Research Ed.). 1996 December 7; 313(7070): 1479-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8973247&dopt=Abstract
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Fatal methadone overdose. Patient may have injected methadone while in hospital. Author(s): Byrne AJ. Source: Bmj (Clinical Research Ed.). 1996 December 7; 313(7070): 1480. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8973248&dopt=Abstract
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Fatal methadone overdose. Sloppy prescribing cannot be totally blamed for deaths from methadone overdose. Author(s): Gabbay M, Perry M. Source: Bmj (Clinical Research Ed.). 1997 July 5; 315(7099): 55-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9233336&dopt=Abstract
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Fatal methadone poisoning in children: Maryland 1992-1996. Author(s): Li L, Levine B, Smialek JE. Source: Substance Use & Misuse. 2000 August; 35(9): 1141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349679&dopt=Abstract
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Fatal methadone toxicity: signs and circumstances, and the role of benzodiazepines. Author(s): Caplehorn JR, Drummer OH. Source: Aust N Z J Public Health. 2002 August; 26(4): 358-62; Discussion 362-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233958&dopt=Abstract
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Fatal poisoning with intravenously injected methadone and no fresh injection marks found. Author(s): Jensen S, Gregersen M. Source: International Journal of Legal Medicine. 1991; 104(5): 299-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1782149&dopt=Abstract
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Fear of methadone maintenance. Author(s): Newman RG. Source: The American Journal of Psychiatry. 1987 March; 144(3): 394-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3826448&dopt=Abstract
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Feasibility of prescribing injectable heroin and methadone to opiate-dependent drug users: associated health gains and harm reductions. Author(s): Metrebian N, Shanahan W, Wells B, Stimson GV. Source: The Medical Journal of Australia. 1998 June 15; 168(12): 596-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9673620&dopt=Abstract
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Financing and cost of standard and enhanced methadone treatment. Author(s): Bradley CJ, French MT, Rachal JV. Source: Journal of Substance Abuse Treatment. 1994 September-October; 11(5): 433-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7869464&dopt=Abstract
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Fluoxetine addition to methadone in addicts: pharmacokinetic aspects. Author(s): Bertschy G, Eap CB, Powell K, Baumann P. Source: Therapeutic Drug Monitoring. 1996 October; 18(5): 570-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885121&dopt=Abstract
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Fluoxetine for cocaine abuse in methadone patients: preliminary findings. Author(s): Batki SL, Manfredi LB, Sorensen JL, Jacob P, Dumontet R, Jones RT. Source: Nida Res Monogr. 1991; 105: 516-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876106&dopt=Abstract
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Fluoxetine for cocaine dependence in methadone maintenance. Author(s): Balon R. Source: Journal of Clinical Psychopharmacology. 1994 October; 14(5): 360-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7806696&dopt=Abstract
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Fluoxetine for cocaine dependence in methadone maintenance: quantitative plasma and urine cocaine/benzoylecgonine concentrations. Author(s): Batki SL, Manfredi LB, Jacob P 3rd, Jones RT. Source: Journal of Clinical Psychopharmacology. 1993 August; 13(4): 243-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8376611&dopt=Abstract
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Fluoxetine treatment for dually diagnosed methadone maintained opioid addicts: a pilot study. Author(s): Petrakis I, Carroll K, Gordon L, Cushing G, Rounsaville B. Source: J Addict Dis. 1994; 13(3): 25-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7734457&dopt=Abstract
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Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts. Author(s): Petrakis I, Carroll KM, Nich C, Gordon L, Kosten T, Rounsaville B. Source: Drug and Alcohol Dependence. 1998 May 1; 50(3): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9649975&dopt=Abstract
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Fluvoxamine and fluoxetine do not interact in the same way with the metabolism of the enantiomers of methadone. Author(s): Eap CB, Bertschy G, Powell K, Baumann P. Source: Journal of Clinical Psychopharmacology. 1997 April; 17(2): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950475&dopt=Abstract
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Fluvoxamine-methadone interaction. Author(s): Alderman CP, Frith PA. Source: The Australian and New Zealand Journal of Psychiatry. 1999 February; 33(1): 99101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10197892&dopt=Abstract
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Follow-up of inpatient cocaine withdrawal for cocaine-using methadone patients. Author(s): Rosenblum A, Foote J, Magura S, Sturiano V, Xu N, Stimmel B. Source: Journal of Substance Abuse Treatment. 1996 November-December; 13(6): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9219143&dopt=Abstract
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Formulation and stability of naltrexone oral liquid for rapid withdrawal from methadone. Author(s): Fawcett JP, Morgan NC, Woods DJ. Source: The Annals of Pharmacotherapy. 1997 November; 31(11): 1291-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9391680&dopt=Abstract
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Gambling among methadone patients. Author(s): Spunt B, Lesieur H, Hunt D, Cahill L. Source: Int J Addict. 1995 June; 30(8): 929-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7558485&dopt=Abstract
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Gas chromatography-mass spectrometry confirmation of Cozart RapiScan saliva methadone and opiates tests. Author(s): Moore L, Wicks J, Spiehler V, Holgate R. Source: Journal of Analytical Toxicology. 2001 October; 25(7): 520-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599594&dopt=Abstract
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Gender differences at admission and follow-up in a sample of methadone maintenance clients. Author(s): Chatham LR, Hiller ML, Rowan-Szal GA, Joe GW, Simpson DD. Source: Substance Use & Misuse. 1999 June; 34(8): 1137-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10359226&dopt=Abstract
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Gender differences in diagnosing antisocial personality disorder in methadone patients. Author(s): Rutherford MJ, Alterman AI, Cacciola JS, Snider EC. Source: The American Journal of Psychiatry. 1995 September; 152(9): 1309-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7653686&dopt=Abstract
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Gender differences in vocational needs and outcomes for methadone treatment clients. Author(s): Karuntzos GT, Caddell JM, Dennis ML. Source: J Psychoactive Drugs. 1994 April-June; 26(2): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7931862&dopt=Abstract
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Gender, cocaine and during-treatment HIV risk reduction among injection opioid users in methadone maintenance. Author(s): Camacho LM, Bartholomew NG, Joe GW, Cloud MA, Simpson DD. Source: Drug and Alcohol Dependence. 1996 May; 41(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793304&dopt=Abstract
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Germany cuts funds for methadone treatment. Author(s): Karcher H. Source: Bmj (Clinical Research Ed.). 1996 March 23; 312(7033): 727. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8605449&dopt=Abstract
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Glucuronidation of 3'-azido-3'-deoxythymidine (zidovudine) by human liver microsomes: relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid. Author(s): Trapnell CB, Klecker RW, Jamis-Dow C, Collins JM. Source: Antimicrobial Agents and Chemotherapy. 1998 July; 42(7): 1592-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9660989&dopt=Abstract
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Gonadal function in male heroin and methadone addicts. Author(s): Ragni G, De Lauretis L, Bestetti O, Sghedoni D, Gambaro V. Source: International Journal of Andrology. 1988 April; 11(2): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3372047&dopt=Abstract
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GPs and methadone. Primum non nocere. Author(s): MacQueen AR. Source: Aust Fam Physician. 1998 June; 27(6): 459-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9648308&dopt=Abstract
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Granulocyte defects and opioid receptors in chronic exposure to heroin or methadone in humans. Author(s): Mazzone A, Mazzucchelli I, Fossati G, Gritti D, Fea M, Ricevuti G. Source: International Journal of Immunopharmacology. 1994 November; 16(11): 959-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7868301&dopt=Abstract
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Group psychotherapy with methadone-maintained pregnant women. Author(s): Mackie-Ramos RL, Rice JM. Source: Journal of Substance Abuse Treatment. 1988; 5(3): 151-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3236389&dopt=Abstract
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Gut motility and transit changes in patients receiving long-term methadone maintenance. Author(s): Yuan CS, Foss JF, O'Connor M, Moss J, Roizen MF. Source: Journal of Clinical Pharmacology. 1998 October; 38(10): 931-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9807974&dopt=Abstract
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Habituation of skin conductance response in a methadone population. Author(s): Loimer N, Jagsch R, Linzmayer L, Grunberger J. Source: Drug and Alcohol Dependence. 1990 October; 26(2): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2242722&dopt=Abstract
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Hair analysis as a tool for monitoring and managing patients on methadone maintenance. A discussion. Author(s): Brewer C. Source: Forensic Science International. 1993 December; 63(1-3): 277-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8138228&dopt=Abstract
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Hallucination during sustained-release morphine and methadone administration. Author(s): Jellema JG. Source: Lancet. 1987 August 15; 2(8555): 392. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2886842&dopt=Abstract
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Hazards of process regulations. The example of methadone maintenance. Author(s): Dole VP. Source: Jama : the Journal of the American Medical Association. 1992 April 22-29; 267(16): 2234-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1556800&dopt=Abstract
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Health status of employed and unemployed methadone patients. Author(s): Widman M, Lidz V, DiGregorio GJ, Platt AK, Robison L, Platt JJ. Source: Journal of Substance Abuse Treatment. 2000 April; 18(3): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10742644&dopt=Abstract
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Heavy drinking in a population of methadone-maintained clients. Author(s): Chatham LR, Rowan-Szal GA, Joe GW, Brown BS, Simpson DD. Source: J Stud Alcohol. 1995 July; 56(4): 417-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7674677&dopt=Abstract
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Heavy drinking, alcohol-dependent vs. nondependent methadone-maintenance clients: a follow-up study. Author(s): Chatham LR, Rowan-Szal GA, Joe GW, Simpson DD. Source: Addictive Behaviors. 1997 January-February; 22(1): 69-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9022873&dopt=Abstract
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Hepatitis C in methadone maintenance patients: prevalence and public policy implications. Author(s): McCarthy JJ, Flynn N. Source: J Addict Dis. 2001; 20(1): 19-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11286428&dopt=Abstract
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Hepatitis C seroprevalence amongst injecting drug users attending a methadone programme. Author(s): Chetwynd J, Brunton C, Blank M, Plumridge E, Baldwin D. Source: N Z Med J. 1995 September 8; 108(1007): 364-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7566775&dopt=Abstract
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Hepatitis C virus and human immunodeficiency virus-1 co-infection in former heroin addicts in methadone maintenance treatment. Author(s): Piccolo P, Borg L, Lin A, Melia D, Ho A, Kreek MJ. Source: J Addict Dis. 2002; 21(4): 55-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296502&dopt=Abstract
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Heroin addiction and methadone maintenance: when will we ever learn. Author(s): Stimmel B. Source: J Addict Dis. 1999; 18(2): 1-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10334371&dopt=Abstract
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Heroin addicts and methadone treatment in Albuquerque: a 22-year follow-up. Author(s): Goldstein A, Herrera J. Source: Drug and Alcohol Dependence. 1995 December; 40(2): 139-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8745136&dopt=Abstract
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Heroin craving and drug use in opioid-maintained volunteers: effects of methadone dose variations. Author(s): Greenwald MK. Source: Experimental and Clinical Psychopharmacology. 2002 February; 10(1): 39-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866251&dopt=Abstract
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Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use. Author(s): Hartel DM, Schoenbaum EE, Selwyn PA, Kline J, Davenny K, Klein RS, Friedland GH. Source: American Journal of Public Health. 1995 January; 85(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7832267&dopt=Abstract
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Heroin users on a methadone programme. Author(s): Onion C, Janikiewicz S. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1993 May; 43(370): 216-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8347391&dopt=Abstract
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Heroin users seeking methadone treatment. Author(s): Caplehorn JR. Source: The Medical Journal of Australia. 1990 September 3; 153(5): 305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2392084&dopt=Abstract
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Heroin users seeking methadone treatment. Author(s): Bell J, Fernandes D, Batey R. Source: The Medical Journal of Australia. 1990 April 2; 152(7): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2093804&dopt=Abstract
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High dose methadone and ventricular arrhythmias: a report of three cases. Author(s): Walker PW, Klein D, Kasza L. Source: Pain. 2003 June; 103(3): 321-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791438&dopt=Abstract
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High dosing methadone and a possible relationship to serious cardia arrhythmias. Author(s): Hays H. Source: Pain Res Manag. 2001 Summer; 6(2): 64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11873731&dopt=Abstract
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High interindividual variability of methadone enantiomer blood levels to dose ratios. Author(s): Eap CB, Bertschy G, Baumann P, Finkbeiner T, Gastpar M, Scherbaum N. Source: Archives of General Psychiatry. 1998 January; 55(1): 89-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9435768&dopt=Abstract
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High sugar intake in a group of women on methadone maintenance in south western Sydney, Australia. Author(s): Zador D, Lyons Wall PM, Webster I. Source: Addiction (Abingdon, England). 1996 July; 91(7): 1053-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8688819&dopt=Abstract
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High-dose methadone and the need for drug measurements in plasma. Author(s): Wolff K, Hay A, Raistrick D. Source: Clinical Chemistry. 1991 September; 37(9): 1651-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1654235&dopt=Abstract
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High-dose methadone produces superior opioid blockade and comparable withdrawal suppression to lower doses in opioid-dependent humans. Author(s): Donny EC, Walsh SL, Bigelow GE, Eissenberg T, Stitzer ML. Source: Psychopharmacology. 2002 May; 161(2): 202-12. Epub 2002 March 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981600&dopt=Abstract
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HIV incidence among injection drug users enrolled in a Los Angeles methadone program. Author(s): Kerndt PR, Weber M, Ford W, Prevots DR, Lehman JS. Source: Jama : the Journal of the American Medical Association. 1995 June 21; 273(23): 1831-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7776493&dopt=Abstract
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HIV infection among injecting drug users in the South Australian methadone program. Author(s): Gaughwin MD, Ali R. Source: The Medical Journal of Australia. 1995 March 6; 162(5): 242-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7891603&dopt=Abstract
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HIV infection and AIDS risk behaviors among injecting drug users entering methadone treatment: an update. Author(s): Battjes RJ, Pickens RW, Brown LS Jr. Source: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association. 1995 September 1; 10(1): 90-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7648291&dopt=Abstract
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HIV infection and AIDS risk behaviors among intravenous drug users entering methadone treatment in selected U.S. cities. Author(s): Battjes RJ, Pickens RW, Amsel Z. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 1991; 4(11): 1148-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1753342&dopt=Abstract
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HIV infection and cocaine use in methadone maintained and untreated intravenous drug users. Author(s): Meandzija B, O'Connor PG, Fitzgerald B, Rounsaville BJ, Kosten TR. Source: Drug and Alcohol Dependence. 1994 October; 36(2): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7851277&dopt=Abstract
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HIV infection risks, behaviors and methadone treatment: client-reported HIV infection in a follow-up study of injecting drug users in New England. Author(s): Brackbill RM, MacGowan RJ, Rugg D. Source: The American Journal of Drug and Alcohol Abuse. 1997 August; 23(3): 397-411. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9261488&dopt=Abstract
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HIV prevalence and risk behavior among injecting drug users who participate in “low-threshold” methadone programs in Amsterdam. Author(s): Hartgers C, van den Hoek A, Krijnen P, Coutinho RA. Source: American Journal of Public Health. 1992 April; 82(4): 547-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1312311&dopt=Abstract
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HIV risk behavior: antisocial personality disorder, drug use patterns, and sexual behavior among methadone maintenance admissions. Author(s): Nolimal D, Crowley TJ. Source: Nida Res Monogr. 1989; 95: 401-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2641008&dopt=Abstract
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HIV risk behaviors among women in methadone maintenance treatment. Author(s): Grella CE, Anglin D, Annon JJ. Source: Substance Use & Misuse. 1996 February; 31(3): 277-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8834263&dopt=Abstract
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HIV risks of men in methadone maintenance treatment programs who abuse their intimate partners: a forgotten issue. Author(s): el-Bassel N, Fontdevila J, Gilbert L, Voisin D, Richman BL, Pitchell P. Source: Journal of Substance Abuse. 2001; 13(1-2): 29-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11547622&dopt=Abstract
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HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment. Author(s): Baker A, Kochan N, Dixon J, Wodak A, Heather N. Source: Addiction (Abingdon, England). 1995 April; 90(4): 545-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7773117&dopt=Abstract
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HIV transmission and the cost-effectiveness of methadone maintenance. Author(s): Zaric GS, Barnett PG, Brandeau ML. Source: American Journal of Public Health. 2000 July; 90(7): 1100-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10897189&dopt=Abstract
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HIV-infected i.v. drug users in methadone treatment: outcome and psychological correlates--a preliminary report. Author(s): Batki SL, Sorensen JL, Gibson DR, Maude-Griffin P. Source: Nida Res Monogr. 1989; 95: 405-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2641010&dopt=Abstract
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HIV-infected intravenous drug users in methadone maintenance treatment: clinical problems and their management. Author(s): Ferrando SJ, Batki SL. Source: J Psychoactive Drugs. 1991 April-June; 23(2): 217-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1662716&dopt=Abstract
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Hormone secretion in methadone-dependent and abstinent patients. Author(s): Woody G, McLellan AT, O'Brien C, Persky H, Stevens G, Arndt I, Carroff S. Source: Nida Res Monogr. 1988; 81: 216-23. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3136363&dopt=Abstract
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Human methadone self-administration: effects of diazepam pretreatment. Author(s): Spiga R, Huang DB, Meisch RA, Grabowski J. Source: Experimental and Clinical Psychopharmacology. 2001 February; 9(1): 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519634&dopt=Abstract
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Hydromorphone polymer implant. A potential alternative to methadone maintenance. Author(s): Rhodes DJ, Grossman SA. Source: Journal of Substance Abuse Treatment. 1997 November-December; 14(6): 535-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9437625&dopt=Abstract
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Hyperalgesic responses in methadone maintenance patients. Author(s): Doverty M, White JM, Somogyi AA, Bochner F, Ali R, Ling W. Source: Pain. 2001 February 1; 90(1-2): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166974&dopt=Abstract
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Hyperphagia in neonates withdrawing from methadone. Author(s): Martinez A, Kastner B, Taeusch HW. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 1999 May; 80(3): F178-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10212077&dopt=Abstract
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Identifying methadone maintenance clients at risk for poor treatment response: pretreatment and early progress indicators. Author(s): Morral AR, Belding MA, Iguchi MY. Source: Drug and Alcohol Dependence. 1999 June 1; 55(1-2): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10402146&dopt=Abstract
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Illicit use of methadone among i.v. drug users in Montreal. Author(s): Lauzon P, Vincelette J, Bruneau J, Lamothe F, Lachance N, Brabant M, Soto J. Source: Journal of Substance Abuse Treatment. 1994 September-October; 11(5): 457-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7869467&dopt=Abstract
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Illicit use of methadone in heroin addicts in Rome. Author(s): Grassi MC, Nencini P, Paroli E. Source: Ann Ist Super Sanita. 1991; 27(4): 671-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1820739&dopt=Abstract
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Imipramine treatment of methadone maintenance patients with affective disorder and illicit drug use. Author(s): Nunes EV, Quitkin FM, Brady R, Stewart JW. Source: The American Journal of Psychiatry. 1991 May; 148(5): 667-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2018172&dopt=Abstract
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Immune function and anti-HTLV-I/II status in anti-HIV-1-negative intravenous drug users receiving methadone. Author(s): Klimas NG, Blaney NT, Morgan RO, Chitwood D, Milles K, Lee H, Fletcher MA. Source: The American Journal of Medicine. 1991 February; 90(2): 163-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1671730&dopt=Abstract
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Immune status of unselected methadone maintained former heroin addicts. Author(s): Kreek MJ, Khuri E, Flomenberg N, Albeck H, Ochshorn M. Source: Prog Clin Biol Res. 1990; 328: 445-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2304962&dopt=Abstract
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Immunohistochemical detection of methadone in the human brain. Author(s): Wehner F, Wehner H, Schieffer MC, Subke J. Source: Forensic Science International. 2000 July 24; 112(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882827&dopt=Abstract
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Immunological function in active heroin addicts and methadone-maintained former addicts: observations and possible mechanisms. Author(s): Kreek MJ. Source: Nida Res Monogr. 1991; 105: 75-81. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876153&dopt=Abstract
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Impact of the AIDS epidemic on morbidity and mortality among intravenous drug users in a New York City methadone maintenance program. Author(s): Selwyn PA, Hartel D, Wasserman W, Drucker E. Source: American Journal of Public Health. 1989 October; 79(10): 1358-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2782502&dopt=Abstract
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Impaired glucose metabolism in heroin and methadone users. Author(s): Ceriello A, Giugliano D, Passariello N, Quatraro A, Dello Russo P, Torella R, D'Onofrio F. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1987 September; 19(9): 430-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3319862&dopt=Abstract
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Implementation of a clinic policy of client-regulated methadone dosing. Author(s): Robles E, Miller FB, Gilmore-Thomas KK, McMillan DE. Source: Journal of Substance Abuse Treatment. 2001 April; 20(3): 225-30; Discussion 231. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516591&dopt=Abstract
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Implementation of the methadone treatment quality assurance system. findings from the feasibility study. Author(s): Ducharme LJ, Luckey JW. Source: Evaluation & the Health Professions. 2000 March; 23(1): 72-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10787952&dopt=Abstract
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Implications of managed care for methadone treatment. Findings from five case studies in New York State. Author(s): Zarkin GA, Dunlap LJ. Source: Journal of Substance Abuse Treatment. 1999 July-September; 17(1-2): 25-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435250&dopt=Abstract
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Implications of methadone maintenance for theories of narcotic addiction. Author(s): Dole VP. Source: Jama : the Journal of the American Medical Association. 1988 November 25; 260(20): 3025-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2846900&dopt=Abstract
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Importance of identifying cocaine and alcohol dependent methadone clients. Author(s): Rowan-Szal GA, Chatham LR, Simpson DD. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2000 Winter; 9(1): 38-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914292&dopt=Abstract
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Improved solid-phase extraction of methadone and its two major metabolites from whole blood. Author(s): Cooper GA, Oliver JS. Source: Journal of Analytical Toxicology. 1998 September; 22(5): 389-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9737334&dopt=Abstract
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Improvement in psychological functioning among drug abusers: inpatient treatment compared to outpatient methadone maintenance. Author(s): Craig RJ, Olson R, Shalton G. Source: Journal of Substance Abuse Treatment. 1990; 7(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2313767&dopt=Abstract
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Improving detoxification outcomes from methadone maintenance treatment: the interrelationship of affective states and protracted withdrawal. Author(s): Latowsky M. Source: J Psychoactive Drugs. 1996 July-September; 28(3): 251-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895110&dopt=Abstract
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Improving treatment engagement and outcomes for cocaine-using methadone patients. Author(s): Villano CL, Rosenblum A, Magura S, Fong C. Source: The American Journal of Drug and Alcohol Abuse. 2002; 28(2): 213-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014813&dopt=Abstract
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In contrast to cocaine, prenatal exposure to methadone does not produce detectable alterations in the developing mouse brain. Author(s): Nassogne MC, Gressens P, Evrard P, Courtoy PJ. Source: Brain Research. Developmental Brain Research. 1998 September 10; 110(1): 61-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9733920&dopt=Abstract
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In vitro interactions between fluoxetine or fluvoxamine and methadone or buprenorphine. Author(s): Iribarne C, Picart D, Dreano Y, Berthou F. Source: Fundamental & Clinical Pharmacology. 1998; 12(2): 194-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9565774&dopt=Abstract
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In vitro studies of the effect of methadone on natural killer cell activity. Author(s): Ochshorn M, Novick DM, Kreek MJ. Source: Isr J Med Sci. 1990 August; 26(8): 421-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2401603&dopt=Abstract
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Inadequate plasma concentrations in some high-dose methadone maintenance patients. Author(s): Tennant FS Jr. Source: The American Journal of Psychiatry. 1987 October; 144(10): 1349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3661772&dopt=Abstract
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Incidence and prevalence of hepatitis C among clients of a Brisbane methadone clinic: factors influencing hepatitis C serostatus. Author(s): Selvey LA, Denton M, Plant AJ. Source: Aust N Z J Public Health. 1997 February; 21(1): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9141740&dopt=Abstract
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Incidence of hepatitis C, hepatitis B and HIV infections among drug users in a methadone-maintenance programme. Author(s): Chamot E, de Saussure P, Hirschel B, Deglon JJ, Perrin LH. Source: Aids (London, England). 1992 April; 6(4): 430-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1616640&dopt=Abstract
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Incidence of HIV infection in a New York City methadone maintenance treatment program. Author(s): Orr MF, Glebatis D, Friedmann P, des Jarlais DC, Prevots DR. Source: Jama : the Journal of the American Medical Association. 1996 July 10; 276(2): 99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8656520&dopt=Abstract
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Increase in deaths due to methadone in North Carolina. Author(s): Ballesteros MF, Budnitz DS, Sanford CP, Gilchrist J, Agyekum GA, Butts J. Source: Jama : the Journal of the American Medical Association. 2003 July 2; 290(1): 40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837709&dopt=Abstract
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Increase in desipramine serum levels associated with methadone treatment. Author(s): Maany I, Dhopesh V, Arndt IO, Burke W, Woody G, O'Brien CP. Source: The American Journal of Psychiatry. 1989 December; 146(12): 1611-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2486749&dopt=Abstract
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Indicators of nutritional status among clients from a New York City methadone treatment center. Author(s): Hebert JR, Nichols SE Jr, Kabat GC. Source: Journal of Substance Abuse Treatment. 1990; 7(3): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2172565&dopt=Abstract
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Individualized use of methadone and opioid rotation in the comprehensive management of cancer pain associated with poor prognostic indicators. Author(s): Vigano A, Fan D, Bruera E. Source: Pain. 1996 September; 67(1): 115-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895238&dopt=Abstract
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Induction of antibodies to methadone during methadone maintenance treatment of heroin addicts and its possible clinical implications. Author(s): Gamaleya N, Dmitrieva I, Borg S, Ericcson N. Source: European Journal of Pharmacology. 1999 March 26; 369(3): 357-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10225375&dopt=Abstract
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Ineffective use of psychoactive drugs. Methadone treatment is no exception. Author(s): Cooper JR. Source: Jama : the Journal of the American Medical Association. 1992 January 8; 267(2): 281-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1727529&dopt=Abstract
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Influence of a methadone maintenance programme on the improved outcome of a cohort on injecting drug users with advanced HIV disease. Author(s): Antela A, Casado JL, Gonzalez MJ, Perez P, Perez-Elias MJ, Montilla P, Buzon L. Source: Aids (London, England). 1997 September; 11(11): 1405-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9302458&dopt=Abstract
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Infrequent neonatal opiate withdrawal following maternal methadone detoxification during pregnancy. Author(s): Maas U, Kattner E, Weingart-Jesse B, Schafer A, Obladen M. Source: Journal of Perinatal Medicine. 1990; 18(2): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2366131&dopt=Abstract
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Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone. Author(s): Wu D, Otton SV, Sproule BA, Busto U, Inaba T, Kalow W, Sellers EM. Source: British Journal of Clinical Pharmacology. 1993 January; 35(1): 30-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8448065&dopt=Abstract
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Inhibition of methadone and buprenorphine N-dealkylations by three HIV-1 protease inhibitors. Author(s): Iribarne C, Berthou F, Carlhant D, Dreano Y, Picart D, Lohezic F, Riche C. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1998 March; 26(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9492389&dopt=Abstract
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Injectable methadone prescribing in the United Kingdom--current practice and future policy guidelines. Author(s): Sarfraz A, Alcorn RJ. Source: Substance Use & Misuse. 1999 October; 34(12): 1709-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10499416&dopt=Abstract
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Injectable methadone: cautious interest. Author(s): Torrens M. Source: Addiction (Abingdon, England). 2000 December; 95(12): 1864-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218365&dopt=Abstract
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Injecting behaviour and risky needle use amongst methadone maintenance clients. Author(s): White JM, Dyer KR, Ali RL, Gaughwin MD, Cormack S. Source: Drug and Alcohol Dependence. 1994 January; 34(2): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8026298&dopt=Abstract
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Integrating primary care and methadone maintenance treatment: implementation issues. Author(s): Herman M, Gourevitch MN. Source: J Addict Dis. 1997; 16(1): 91-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9046446&dopt=Abstract
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Integrating the methadone patient in the traditional addiction inpatient rehabilitation program--problems and solutions. Author(s): Kipnis SS, Herron A, Perez J, Joseph H. Source: The Mount Sinai Journal of Medicine, New York. 2001 January; 68(1): 28-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135503&dopt=Abstract
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Integrative modeling of client engagement and outcomes during the first 6 months of methadone treatment. Author(s): Joe GW, Simpson DD, Greener JM, Rowan-Szal GA. Source: Addictive Behaviors. 1999 September-October; 24(5): 649-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10574302&dopt=Abstract
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Interaction of methadone with didanosine and stavudine. Author(s): Rainey PM, Friedland G, McCance-Katz EF, Andrews L, Mitchell SM, Charles C, Jatlow P. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2000 July 1; 24(3): 241-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969348&dopt=Abstract
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Interaction of methadone with substrates of human hepatic cytochrome P450 3A4. Author(s): Iribarne C, Dreano Y, Bardou LG, Menez JF, Berthou F. Source: Toxicology. 1997 February 14; 117(1): 13-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9020195&dopt=Abstract
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Interactions between methadone and medications used to treat HIV infection: a review. Author(s): Gourevitch MN, Friedland GH. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 429-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064494&dopt=Abstract
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Interest in smoking cessation among methadone maintained outpatients. Author(s): Frosch DL, Shoptaw S, Jarvik ME, Rawson RA, Ling W. Source: J Addict Dis. 1998; 17(2): 9-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9567223&dopt=Abstract
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Interim methadone clinics: an undervalued approach. Author(s): Dole VP. Source: American Journal of Public Health. 1991 September; 81(9): 1111-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1659235&dopt=Abstract
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Interindividual dose/concentration relationship for methadone in hair. Author(s): Paterson S, Cordero R, McPhillips M, Carman S. Source: Journal of Analytical Toxicology. 2003 January-February; 27(1): 20-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587678&dopt=Abstract
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Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Author(s): Eap CB, Buclin T, Baumann P. Source: Clinical Pharmacokinetics. 2002; 41(14): 1153-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405865&dopt=Abstract
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Interruption of methadone treatment by imprisonment. Author(s): Gruer L, Macleod J. Source: Bmj (Clinical Research Ed.). 1997 June 7; 314(7095): 1691. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9193305&dopt=Abstract
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Intimate partner sexual abuse among women on methadone. Author(s): Frye V, El-Bassel N, Gilbert L, Rajah V, Christie N. Source: Violence Vict. 2001 October; 16(5): 553-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11688929&dopt=Abstract
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Intrathecal methadone and morphine for postoperative analgesia: a comparison of the efficacy, duration, and side effects. Author(s): Jacobson L, Chabal C, Brody MC, Ward RJ, Ireton RC. Source: Anesthesiology. 1989 May; 70(5): 742-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2655501&dopt=Abstract
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Intrathecal methadone: a dose-response study and comparison with intrathecal morphine 0.5 mg. Author(s): Jacobson L, Chabal C, Brody MC, Ward RJ, Wasse L. Source: Pain. 1990 November; 43(2): 141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2087326&dopt=Abstract
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Intravenous drug use, methadone, and AIDS: ask not for whom the bell tolls. Author(s): Stimmel B. Source: J Addict Dis. 1993; 12(1): 1-5. No Abstract Available. Erratum In: J Addict Dis 1993; 12(2): Preceding 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8424962&dopt=Abstract
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Intravenous heroin use: its association with HIV infection in patients in methadone treatment. Author(s): Chu A, Brown LS, Banks S, Nemoto T, Primm BJ. Source: Nida Res Monogr. 1989; 95: 447-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2641025&dopt=Abstract
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Intravenous high-dose methadone administered by patient controlled analgesia and continuous infusion for the treatment of cancer pain refractory to high-dose morphine. Author(s): Fitzgibbon DR, Ready LB. Source: Pain. 1997 November; 73(2): 259-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415514&dopt=Abstract
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Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations. Author(s): Manfredi PL, Borsook D, Chandler SW, Payne R. Source: Pain. 1997 March; 70(1): 99-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9106815&dopt=Abstract
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Intravenous methadone in the management of chronic cancer pain: safe and effective starting doses when substituting methadone for fentanyl. Author(s): Santiago-Palma J, Khojainova N, Kornick C, Fischberg DJ, Primavera LH, Payne R, Manfredi P. Source: Cancer. 2001 October 1; 92(7): 1919-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745266&dopt=Abstract
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Investigating the influence of treatment philosophy on outcome of methadone maintenance. Author(s): Bell J, Chan J, Kuk A. Source: Addiction (Abingdon, England). 1995 June; 90(6): 823-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7633300&dopt=Abstract
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Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Author(s): Iribarne C, Berthou F, Baird S, Dreano Y, Picart D, Bail JP, Beaune P, Menez JF. Source: Chemical Research in Toxicology. 1996 March; 9(2): 365-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8839037&dopt=Abstract
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Irish prison guards call for expansion of methadone access. Author(s): Lines R. Source: Can Hiv Aids Policy Law Rev. 2001; 6(1-2): 71-4. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837036&dopt=Abstract
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Is methadone a miracle cure or an alternative evil? Author(s): Hoffman RS. Source: The Western Journal of Medicine. 2000 January; 172(1): 15-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695435&dopt=Abstract
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Ischemia of the hand due to intraarterial injection of dissolved methadone tablets. Author(s): Greif F, Cohen N, Weiss J, Rozin RR, Skornick Y. Source: Isr J Med Sci. 1987 November; 23(11): 1166-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3436804&dopt=Abstract
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Ketoconazole increases cocaine and opioid use in methadone maintained patients. Author(s): Kosten TR, Oliveto A, Sevarino KA, Gonsai K, Feingold A. Source: Drug and Alcohol Dependence. 2002 April 1; 66(2): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906804&dopt=Abstract
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LAAM maintenance vs methadone maintenance for heroin dependence. Author(s): Cochrane Database Syst Rev. 2003;(2):CD003409 Source: Cochrane Database Syst Rev. 2002; (2): Cd002210. Review. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12804464
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Lack of a pharmacologic interaction between rifabutin and methadone in HIVinfected former injecting drug users. Author(s): Brown LS, Sawyer RC, Li R, Cobb MN, Colborn DC, Narang PK. Source: Drug and Alcohol Dependence. 1996 December 2; 43(1-2): 71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8957145&dopt=Abstract
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Lack of methadone dose alterations or withdrawal symptoms during therapy with lopinavir/ritonavir. Author(s): Stevens RC, Rapaport S, Maroldo-Connelly L, Patterson JB, Bertz R. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 August 15; 33(5): 650-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902812&dopt=Abstract
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LC-atmospheric pressure chemical ionization-MS/ MS analysis of multiple illicit drugs, methadone, and their metabolites in oral fluid following protein precipitation. Author(s): Dams R, Murphy CM, Choo RE, Lambert WE, De Leenheer AP, Huestis MA. Source: Analytical Chemistry. 2003 February 15; 75(4): 798-804. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622369&dopt=Abstract
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Leaving methadone treatment: lessons learned, lessons forgotten, lessons ignored. Author(s): Magura S, Rosenblum A. Source: The Mount Sinai Journal of Medicine, New York. 2001 January; 68(1): 62-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135508&dopt=Abstract
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Legality of methadone treatment. Author(s): Peyser NP. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 1993 May; 8(5): 286. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8389402&dopt=Abstract
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Less driving impairment on buprenorphine than methadone in drug-dependent patients? Author(s): Soyka M, Horak M, Dittert S, Kagerer S. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2001 Fall; 13(4): 527-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748323&dopt=Abstract
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Lessons from a training program for methadone prescribers. Author(s): Bell JR. Source: The Medical Journal of Australia. 1995 February 6; 162(3): 143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7854227&dopt=Abstract
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Lethal methadone intoxications in Geneva, Switzerland, from 1994 to 1998. Author(s): Perret G, Deglon JJ, Kreek MJ, Ho A, La Harpe R. Source: Addiction (Abingdon, England). 2000 November; 95(11): 1647-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219368&dopt=Abstract
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Levels of intravenous drug misuse among clients prescribed oral dexamphetamine or oral methadone: a comparison. Author(s): Charnaud B, Griffiths V. Source: Drug and Alcohol Dependence. 1998 September 1; 52(1): 79-84. Erratum In: Drug Alcohol Depend 1999 April 1; 54(2): 179. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9788010&dopt=Abstract
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Life activities and life quality of heroin addicts in and out of methadone treatment. Author(s): Reno RR, Aiken LS. Source: Int J Addict. 1993 February; 28(3): 211-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8440536&dopt=Abstract
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Linking drug-related activities with experiences of partner violence: a focus group study of women in methadone treatment. Author(s): Gilbert L, El-Bassel N, Rajah V, Foleno A, Frye V. Source: Violence Vict. 2001 October; 16(5): 517-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11688927&dopt=Abstract
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Literature on methadone maintenance clinics. Author(s): Liappas JA, Jenner FA, Vicente B. Source: Int J Addict. 1988 September; 23(9): 927-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3069755&dopt=Abstract
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Liver transplantation for patients on methadone maintenance. Author(s): Kanchana TP, Kaul V, Manzarbeitia C, Reich DJ, Hails KC, Munoz SJ, Rothstein KD. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 September; 8(9): 778-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200777&dopt=Abstract
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L-Methadone and D,L-methadone in methadone maintenance treatment: a comparison of therapeutic effectiveness and plasma concentrations. Author(s): de Vos JW, Ufkes JG, Kaplan CD, Tursch M, Krause JK, van Wilgenburg H, Woodcock BG, Staib AH. Source: European Addiction Research. 1998 September; 4(3): 134-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9742275&dopt=Abstract
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Local toxicity with subcutaneous methadone. Experience of two centers. Author(s): Bruera E, Fainsinger R, Moore M, Thibault R, Spoldi E, Ventafridda V. Source: Pain. 1991 May; 45(2): 141-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876420&dopt=Abstract
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Long-term methadone maintenance treatment: some clinical examples. Author(s): Weinstein SP, Gottheil E, Sterling RC, DeMaria PA Jr. Source: Journal of Substance Abuse Treatment. 1993 May-June; 10(3): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8315701&dopt=Abstract
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Long-term methadone treatment: effect on CD4+ lymphocyte counts and HIV-1 plasma RNA level in patients with HIV infection. Author(s): Quang-Cantagrel ND, Wallace MS, Ashar N, Mathews C. Source: European Journal of Pain (London, England). 2001; 5(4): 415-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743707&dopt=Abstract
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Long-term outcomes of protease inhibitor-based therapy in antiretroviral treatmentnaive HIV-infected injection drug users on methadone maintenance programmes. Author(s): Moreno A, Perez-Elias MJ, Casado JL, Munoz V, Antela A, Dronda F, Navas E, Moreno S. Source: Aids (London, England). 2001 May 25; 15(8): 1068-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399995&dopt=Abstract
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Long-term stability of methadone in clinical plasma samples stored at -20 degrees C. Author(s): Lopez ML, Bano MD, Guillen JL. Source: Journal of Analytical Toxicology. 2002 May-June; 26(4): 236-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054366&dopt=Abstract
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Low (40 mg) versus high (80 mg) dose methadone in a 180-day heroin detoxification program. Author(s): Banys P, Tusel DJ, Sees KL, Reilly PM, Delucchi KL. Source: Journal of Substance Abuse Treatment. 1994 May-June; 11(3): 225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8072050&dopt=Abstract
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Low prevalence of human immunodeficiency virus infection in methadone program attenders and pregnant intravenous drug users in the western metropolitan region of Sydney. Author(s): Dwyer D, Bell J, Batey R, Sanders F, Patterson T, Howard R, Downie J, Packham DR, Cunningham AL. Source: Aust N Z J Med. 1989 August; 19(4): 407-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2789510&dopt=Abstract
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Low threshold methadone: a comment on Negrete. Author(s): Perreault M, Mercier C, Lauzon P. Source: Addiction (Abingdon, England). 2001 November; 96(11): 1669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791506&dopt=Abstract
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Low-cost contingency management for treating cocaine- and opioid-abusing methadone patients. Author(s): Petry NM, Martin B. Source: Journal of Consulting and Clinical Psychology. 2002 April; 70(2): 398-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952198&dopt=Abstract
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Maintenance therapy for opioid addiction with methadone, LAAM and buprenorphine: the Emperor's New Clothes Phenomenon. Author(s): Stimmel B. Source: J Addict Dis. 2001; 20(4): 1-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11760922&dopt=Abstract
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Measuring the value of time for methadone maintenance clients: willingness to pay, willingness to accept, and the wage rate. Author(s): Borisova NN, Goodman AC. Source: Health Economics. 2003 April; 12(4): 323-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652518&dopt=Abstract
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Medico-legal rounds: medico-legal issues and alleged breaches of “standards of medical care” in opioid rotation to methadone: a case report. Author(s): Fishbain DA, Cutler RB, Cole B, Lewis J, Rosomoff RS, Rosomoff HL. Source: Pain Medicine (Malden, Mass.). 2003 June; 4(2): 195-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873269&dopt=Abstract
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Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation. Author(s): Oda Y, Kharasch ED. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 September; 298(3): 1021-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11504799&dopt=Abstract
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Methadone and anti-HIV drugs. Author(s): Fornataro K. Source: Body Posit. 1999 May; 12(5): 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11366305&dopt=Abstract
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Methadone and antiretroviral medications, part I. Author(s): Gourevitch MN, Friedland GH. Source: Aids Clin Care. 1999 April; 11(4): 30-1 Contd. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11366210&dopt=Abstract
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Methadone and antiretroviral medications, part II. Author(s): Gourevitch MN, Friedland GH. Source: Aids Clin Care. 1999 May; 11(5): 37, 43, 45-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11367102&dopt=Abstract
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Methadone and breastfeeding: new horizons. Author(s): Philipp BL, Merewood A, O'Brien S. Source: Pediatrics. 2003 June; 111(6 Pt 1): 1429-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777563&dopt=Abstract
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Methadone and fluconazole: respiratory depression by drug interaction. Author(s): Tarumi Y, Pereira J, Watanabe S. Source: Journal of Pain and Symptom Management. 2002 February; 23(2): 148-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844635&dopt=Abstract
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Methadone and heroin prescription: babies and bath water. Author(s): Wodak A. Source: Substance Use & Misuse. 2002 March; 37(4): 523-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064432&dopt=Abstract
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Methadone and its role in drug-related fatalities in Cologne 1989-2000. Author(s): Grass H, Behnsen S, Kimont HG, Staak M, Kaferstein H. Source: Forensic Science International. 2003 April 8; 132(3): 195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711204&dopt=Abstract
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Methadone and neonatal thrombocytosis. Author(s): Garcia-Algar O, Brichs LF, Garcia ES, Fabrega DM, Torne EE, Sierra AM. Source: Pediatric Hematology and Oncology. 2002 April-May; 19(3): 193-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936732&dopt=Abstract
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Methadone and the pregnant user: a matter for careful clinical consideration. Author(s): Hulse GK, O'Neill G. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2001 August; 41(3): 329-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592552&dopt=Abstract
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Methadone at tapered doses for the management of opioid withdrawal. Author(s): Amato L, Davoli M, Ferri M, Ali R. Source: Cochrane Database Syst Rev. 2003; (3): Cd003409. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917966&dopt=Abstract
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Methadone at tapered doses for the management of opioid withdrawal. Author(s): Amato L, Davoli M, Ferri M, Ali R. Source: Cochrane Database Syst Rev. 2003; (2): Cd003409. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804464&dopt=Abstract
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Methadone at tapered doses for the management of opioid withdrawal. Author(s): Amato L, Davoli M, Ferri M, Ali R. Source: Cochrane Database Syst Rev. 2002; (2): Cd003409. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076479&dopt=Abstract
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Methadone at tapered doses for the management of opioid withdrawal. Author(s): Amato L, Davoli M, Ferri M, Ali R. Source: Cochrane Database Syst Rev. 2002; (1): Cd003409. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869660&dopt=Abstract
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Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir. Author(s): Bart PA, Rizzardi PG, Gallant S, Golay KP, Baumann P, Pantaleo G, Eap CB. Source: Therapeutic Drug Monitoring. 2001 October; 23(5): 553-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591903&dopt=Abstract
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Methadone dependence and its effects on consecutive pregnancies. Author(s): Siney C, Shaw NJ, McCarthy JE. Source: Pract Midwife. 2000 October; 3(9): 34-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026550&dopt=Abstract
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Methadone enhances human immunodeficiency virus infection of human immune cells. Author(s): Li Y, Wang X, Tian S, Guo CJ, Douglas SD, Ho WZ. Source: The Journal of Infectious Diseases. 2002 January 1; 185(1): 118-22. Epub 2001 December 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756991&dopt=Abstract
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Methadone for phantom limb pain. Author(s): Bergmans L, Snijdelaar DG, Katz J, Crul BJ. Source: The Clinical Journal of Pain. 2002 May-June; 18(3): 203-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048424&dopt=Abstract
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Methadone for refractory cancer pain. Author(s): Shaiova L, Sperber KT, Hord ED. Source: Journal of Pain and Symptom Management. 2002 March; 23(3): 178-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888714&dopt=Abstract
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Methadone for relief of cancer pain: a review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Author(s): Davis MP, Walsh D. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2001 March; 9(2): 73-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305074&dopt=Abstract
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Methadone in provincial prisons in British Columbia. Author(s): Rothon DA. Source: Can Hiv Aids Policy Law Newsl. 1997-98 Winter; 3-4(4-1): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11365288&dopt=Abstract
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Methadone in treatment of tenesmus not responding to morphine escalation. Author(s): Mercadante S, Fulfaro F, Dabbene M. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2001 March; 9(2): 129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305071&dopt=Abstract
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Methadone induces CCR5 and promotes AIDS virus infection. Author(s): Suzuki S, Carlos MP, Chuang LF, Torres JV, Doi RH, Chuang RY. Source: Febs Letters. 2002 May 22; 519(1-3): 173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023039&dopt=Abstract
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Methadone inhibits rhodamine123 transport in Caco-2 cells. Author(s): Stormer E, Perloff MD, von Moltke LL, Greenblatt DJ. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 July; 29(7): 954-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408360&dopt=Abstract
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Methadone is a medication, not an addiction. Author(s): Koch M, Banys P. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 September; 8(9): 783-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200778&dopt=Abstract
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Methadone is safe for treating hospitalized patients with severe pain. Author(s): Shir Y, Rosen G, Zeldin A, Davidson EM. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2001 December; 48(11): 1109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744587&dopt=Abstract
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Methadone maintenance as HIV risk reduction with street-recruited injecting drug users. Author(s): Kwiatkowski CF, Booth RE. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2001 April 15; 26(5): 483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391170&dopt=Abstract
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Methadone maintenance at different dosages for opioid dependence. Author(s): Faggiano F, Vigna-Taglianti F, Versino E, Lemma P. Source: Cochrane Database Syst Rev. 2003; (3): Cd002208. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917925&dopt=Abstract
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Methadone maintenance expands inside federal prisons. Author(s): Sibbald B. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 November 12; 167(10): 1154. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427715&dopt=Abstract
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Methadone maintenance in primary care: a randomized controlled trial. Author(s): Fiellin DA, O'Connor PG, Chawarski M, Pakes JP, Pantalon MV, Schottenfeld RS. Source: Jama : the Journal of the American Medical Association. 2001 October 10; 286(14): 1724-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594897&dopt=Abstract
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Methadone maintenance patients are cross-tolerant to the antinociceptive effects of morphine. Author(s): Doverty M, Somogyi AA, White JM, Bochner F, Beare CH, Menelaou A, Ling W. Source: Pain. 2001 August; 93(2): 155-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427327&dopt=Abstract
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Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Author(s): Cochrane Database Syst Rev. 2003;(3):CD003409 Source: Cochrane Database Syst Rev. 2003; (2): Cd002209. Review. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12917966
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Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Author(s): Mattick RP, Breen C, Kimber J, Davoli M. Source: Cochrane Database Syst Rev. 2002; (4): Cd002209. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519570&dopt=Abstract
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Methadone maintenance treatment can be provided in a primary care setting without increasing methadone-related mortality: the Sheffield experience 1997-2000. Author(s): Keen J, Oliver P, Mathers N. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 May; 52(478): 387-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014536&dopt=Abstract
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Methadone maintenance treatment, criminality and overdose-related deaths. An ecological study, 1983-1999. Author(s): Niveau G, Rougemont AL, La Harpe R. Source: European Journal of Public Health. 2002 September; 12(3): 224-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12232963&dopt=Abstract
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Methadone maintenance. Author(s): Stancliff S. Source: American Family Physician. 2001 June 15; 63(12): 2335-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430450&dopt=Abstract
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Methadone maintenance: its future in skilled nursing facilities. Author(s): Goldberg RJ, Grabowski R. Source: Journal of the American Medical Directors Association. 2003 March-April; 4(2): 98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807582&dopt=Abstract
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Methadone may promote HIV replication: study. Author(s): Douglas SD. Source: Aids Alert. 2001 September; 16(9): 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11547497&dopt=Abstract
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Methadone overdoses increase at alarming rate. Author(s): Payton R. Source: Todays Fda. 2003 February; 15(2): 18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674717&dopt=Abstract
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Methadone prescribing to opiate addicts by private doctors: comparison with NHS practice in south east England. Author(s): Strang J, Sheridan J. Source: Addiction (Abingdon, England). 2001 April; 96(4): 567-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300960&dopt=Abstract
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Methadone substitution: medicolegal problems in Germany. Author(s): Musshoff F, Lachenmeier DW, Madea B. Source: Forensic Science International. 2003 April 23; 133(1-2): 118-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742698&dopt=Abstract
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Methadone syrup injection in Australia: a sentinel finding? Author(s): Fiellin DA. Source: Addiction (Abingdon, England). 2003 April; 98(4): 385-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653807&dopt=Abstract
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Methadone tapering plus amantadine to detoxify heroin-dependent inpatients with or without an active cocaine use disorder: two randomised controlled trials. Author(s): Perez de los Cobos J, Duro P, Trujols J, Tejero A, Batlle F, Ribalta E, Casas M. Source: Drug and Alcohol Dependence. 2001 July 1; 63(2): 187-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376923&dopt=Abstract
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Methadone therapy for opioid dependence. Author(s): Krambeer LL, von McKnelly W Jr, Gabrielli WF Jr, Penick EC. Source: American Family Physician. 2001 June 15; 63(12): 2404-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430455&dopt=Abstract
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Methadone treatment and needle use prevention. Author(s): Iguchi M. Source: Focus. 2002 February; 17(3): 5-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968160&dopt=Abstract
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Methadone treatment in Ontario after the 1996 regulation reforms. Results of a physician survey. Author(s): Cochrane Database Syst Rev. 2003;(2):CD002207 Source: Annales De Medecine Interne. 2002 November; 153(7 Suppl): 2S11-21. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12804429
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Methadone treatment induces attenuation of cerebrovascular deficits associated with the prolonged abuse of cocaine and heroin. Author(s): Herning RI, Better WE, Tate K, Umbricht A, Preston KL, Cadet JL. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 March; 28(3): 562-8. Epub 2002 September 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629538&dopt=Abstract
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Methadone treatment outcomes appear mainly unaffected by cannabis use. Author(s): Seivewright N. Source: Addiction (Abingdon, England). 2003 March; 98(3): 251-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603223&dopt=Abstract
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Methadone treatment: common questions, a common answer. Author(s): Newman RG. Source: Annales De Medecine Interne. 2001 November; 152 Suppl 7: 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965091&dopt=Abstract
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Methadone treatment: our vision for the future. Author(s): McCaffrey BR. Source: J Addict Dis. 2001; 20(1): 93-101. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11286435&dopt=Abstract
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Methadone trough levels in pregnancy. Author(s): Drozdick J 3rd, Berghella V, Hill M, Kaltenbach K. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 1184-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439500&dopt=Abstract
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Methadone use in cancer patients with pain: a review. Author(s): Bruera E, Sweeney C. Source: Journal of Palliative Medicine. 2002 February; 5(1): 127-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839235&dopt=Abstract
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Methadone, but no needle exchange pilot in Federal prisons. Author(s): Jurgens R. Source: Can Hiv Aids Policy Law Newsl. 1997-98 Winter; 3-4(4-1): 26-7, 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11365287&dopt=Abstract
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Methadone, morphine and PTSD. Author(s): Macleod AD, Duffy SG. Source: The Australian and New Zealand Journal of Psychiatry. 2002 December; 36(6): 816-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406127&dopt=Abstract
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Methadone: the question or the answer for US opioid therapy and pharmacoeconomics? Author(s): Dickerson ED. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2001 November; 9(8): 646-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762977&dopt=Abstract
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Methadone: the renaissance. Author(s): Watanabe S. Source: Journal of Palliative Care. 2001 Summer; 17(2): 117-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477986&dopt=Abstract
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Methadone-induced myoclonus in advanced cancer. Author(s): Sarhill N, Davis MP, Walsh D, Nouneh C. Source: Am J Hosp Palliat Care. 2001 January-February; 18(1): 51-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406880&dopt=Abstract
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Methadone-related and heroin-related deaths among opiate users: methadone helps save lives. Author(s): Mattick RP, Degenhardt L. Source: Addiction (Abingdon, England). 2003 April; 98(4): 387-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653808&dopt=Abstract
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Methadone-related deaths and mortality rate during induction into methadone maintenance, New South Wales, 1996. Author(s): Zador DA, Sunjic SD. Source: Drug and Alcohol Review. 2002 June; 21(2): 131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188991&dopt=Abstract
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Methadone-related deaths in Hennepin County, Minnesota: 1992-2002. Author(s): Gagajewski A, Apple FS. Source: J Forensic Sci. 2003 May; 48(3): 668-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762545&dopt=Abstract
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Methadone-related deaths in Scotland: areas for concern. Author(s): Bruce M, Jay J, Robertson R, Robinson A, Squires T. Source: Addiction (Abingdon, England). 2002 March; 97(3): 371. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964115&dopt=Abstract
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Methadone-related deaths in Western Australia 1993-99. Author(s): Ernst E, Bartu A, Popescu A, Ileutt KF, Hansson R, Plumley N. Source: Aust N Z J Public Health. 2002 August; 26(4): 364-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233959&dopt=Abstract
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Motherhood and methadone. Author(s): Hampshire M. Source: Nurs Times. 2000 October 19-25; 96(42): 14. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968613&dopt=Abstract
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Myocardial Infarction associated with methadone and/or dihydrocodeine. Author(s): Backmund M, Meyer K, Zwehl W, Nagengast O, Eichenlaub D. Source: European Addiction Research. 2001 March; 7(1): 37-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316924&dopt=Abstract
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Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long-term methadone maintenance patients. Author(s): Novick DM, Ochshorn M, Ghali V, Croxson TS, Mercer WD, Chiorazzi N, Kreek MJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 1989 August; 250(2): 606-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2788218&dopt=Abstract
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Nebulized naloxone gently and effectively reverses methadone intoxication. Author(s): Mycyk MB, Szyszko AL, Aks SE. Source: The Journal of Emergency Medicine. 2003 February; 24(2): 185-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609650&dopt=Abstract
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Need for medical and psychosocial services among injection drug users: a comparative study of needle exchange and methadone maintenance. Author(s): Stein MD, Friedmann P. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2002 Fall; 11(4): 262-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584869&dopt=Abstract
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Neonatal abstinence syndrome after maternal methadone treatment. Author(s): Shaw NJ, McIvor L. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 1994 November; 71(3): F203-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7820717&dopt=Abstract
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Neonatal outcome following methadone exposure in utero. Author(s): Hagopian GS, Wolfe HM, Sokol RJ, Ager JW, Wardell JN, Cepeda EE. Source: The Journal of Maternal-Fetal Medicine. 1996 November-December; 5(6): 348-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8972413&dopt=Abstract
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Neonatal withdrawal following pre- and postnatal exposure to methadone in the rat. Author(s): Barr GA, Zmitrovich A, Hamowy AS, Liu PY, Wang S, Hutchings DE. Source: Pharmacology, Biochemistry, and Behavior. 1998 May; 60(1): 97-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9610930&dopt=Abstract
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Neonatal withdrawal syndrome in infants exposed to cocaine and methadone. Author(s): Mayes LC, Carroll KM. Source: Substance Use & Misuse. 1996 January; 31(2): 241-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8834011&dopt=Abstract
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Nervous regulation of breathing in opiate dependent patient. Part II. Respiratory system efficiency and breathing regulation of persons classified to the methadone maintenance treatment. Author(s): Kolarzyk E, Targosz D, Pach D, Misiolek L. Source: Przegl Lek. 2000; 57(10): 536-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199881&dopt=Abstract
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Neurobehavioral treatment for cocaine-using methadone patients: a preliminary report. Author(s): Magura S, Rosenblum A, Lovejoy M, Handelsman L, Foote J, Stimmel B. Source: J Addict Dis. 1994; 13(4): 143-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7734465&dopt=Abstract
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Neurobiology of addictive behaviors and its relationship to methadone maintenance. Author(s): Stimmel B, Kreek MJ. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 375-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064487&dopt=Abstract
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Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone. Author(s): Altice FL, Friedland GH, Cooney EL. Source: Aids (London, England). 1999 May 28; 13(8): 957-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371177&dopt=Abstract
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Nevirapine-induced withdrawal symptoms in HIV patients on methadone maintenance programme: an alert. Author(s): Otero MJ, Fuertes A, Sanchez R, Luna G. Source: Aids (London, England). 1999 May 28; 13(8): 1004-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371190&dopt=Abstract
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Nicotine dependence and depression among methadone maintenance patients. Author(s): Meyer TJ, Lin MM, Brown LS Jr. Source: Journal of the National Medical Association. 1996 December; 88(12): 800-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8990806&dopt=Abstract
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No seroconversions among steady sex partners of methadone-maintained HIV-1seropositive injecting drug users in New York City. Author(s): Siddiqui NS, Brown LS Jr, Phillips RY, Vargas O, Makuch RW. Source: Aids (London, England). 1992 December; 6(12): 1529-33. Erratum In: Aids 1993 March; 7(3): Following 444. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1492936&dopt=Abstract
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Node-link mapping for counseling cocaine users in methadone treatment. Author(s): Joe GW, Dansereau DF, Simpson DD. Source: Journal of Substance Abuse. 1994; 6(4): 393-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7780297&dopt=Abstract
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Nonaccidental methadone poisoning. Author(s): Lee AC, Lam SY. Source: Clinical Pediatrics. 2002 June; 41(5): 365-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086206&dopt=Abstract
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Nonconventional opioid binding sites mediate growth inhibitory effects of methadone on human lung cancer cells. Author(s): Maneckjee R, Minna JD. Source: Proceedings of the National Academy of Sciences of the United States of America. 1992 February 15; 89(4): 1169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1311082&dopt=Abstract
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Non-prescribed drug use during methadone treatment by clinic- and communitybased patients. Author(s): Wolff K, Hay AW, Vail A, Harrison K, Raistrick D. Source: Addiction (Abingdon, England). 1996 November; 91(11): 1699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8972927&dopt=Abstract
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Not the picture of health: women on methadone. Author(s): Rosenbaum M, Murphy S. Source: J Psychoactive Drugs. 1987 April-June; 19(2): 217-26. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3612387&dopt=Abstract
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Novel high-performance liquid chromatographic and solid-phase extraction methods for quantitating methadone and its metabolite in spiked human urine. Author(s): Cheng YF, Neue UD, Woods LL. Source: J Chromatogr B Biomed Sci Appl. 1999 June 11; 729(1-2): 19-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10410924&dopt=Abstract
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Office-based methadone prescribing: acceptance by inner-city practitioners in New York. Author(s): McNeely J, Drucker E, Hartel D, Tuchman E. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2000 March; 77(1): 96-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741845&dopt=Abstract
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On federal regulation of methadone treatment. Author(s): Dole VP. Source: Jama : the Journal of the American Medical Association. 1995 October 25; 274(16): 1307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7563538&dopt=Abstract
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On the usefulness of therapeutic drug monitoring of methadone. Author(s): Eap CB. Source: European Addiction Research. 2000 March; 6(1): 31-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10729740&dopt=Abstract
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One-year follow-up of opiate injectors treated with oral methadone in a GP-centred programme. Author(s): Hutchinson SJ, Taylor A, Gruer L, Barr C, Mills C, Elliott L, Goldberg DJ, Scott R, Gilchrist G. Source: Addiction (Abingdon, England). 2000 July; 95(7): 1055-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962770&dopt=Abstract
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One-year mortality rates following methadone treatment discharge. Author(s): Zanis DA, Woody GE. Source: Drug and Alcohol Dependence. 1998 November 1; 52(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839152&dopt=Abstract
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Open letter to doctors and dentists--pain relief in patients on methadone. Author(s): Byrne A. Source: Aust Dent J. 1994 June; 39(3): 194. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8067942&dopt=Abstract
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Opiate addiction and the locus coeruleus. The clinical utility of clonidine, naltrexone, methadone, and buprenorphine. Author(s): Gold MS. Source: The Psychiatric Clinics of North America. 1993 March; 16(1): 61-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8456048&dopt=Abstract
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Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine. Author(s): Janiri L, Mannelli P, Persico AM, Serretti A, Tempesta E. Source: Drug and Alcohol Dependence. 1994 October; 36(2): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7851281&dopt=Abstract
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Opiate withdrawal symptoms in response to 10-day and 21-day methadone withdrawal programmes. Author(s): Gossop M, Griffiths P, Bradley B, Strang J. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1989 March; 154: 360-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2688778&dopt=Abstract
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Opiate-dependent patients receiving methadone. How physicians should manage therapy. Author(s): Kahan M, Sutton N. Source: Can Fam Physician. 1996 September; 42: 1769-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828879&dopt=Abstract
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Opioid plasma concentration during switching from morphine to methadone: preliminary data. Author(s): Mercadante S, Bianchi M, Villari P, Ferrera P, Casuccio A, Fulfaro F, Gebbia V. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 May; 11(5): 326-31. Epub 2003 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690541&dopt=Abstract
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Opioid receptors on white blood cells: effect of HIV infection and methadone treatment. Author(s): Beck M, Mirmohammadsadegh A, Franz B, Blanke J, Hengge UR. Source: Pain. 2002 July; 98(1-2): 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098631&dopt=Abstract
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Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Author(s): Bruera E, Pereira J, Watanabe S, Belzile M, Kuehn N, Hanson J. Source: Cancer. 1996 August 15; 78(4): 852-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8756381&dopt=Abstract
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Opioid rotation to methadone: proceed with caution. Author(s): Watanabe S, Tarumi Y, Oneschuk D, Lawlor P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 May 1; 20(9): 2409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981018&dopt=Abstract
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Opioid switch to oral methadone in cancer pain. Author(s): Mancini I, Lossignol DA, Body JJ. Source: Current Opinion in Oncology. 2000 July; 12(4): 308-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10888415&dopt=Abstract
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Opioid tolerance in human placenta due to in vitro methadone administration. Author(s): Cemerikic B, Zamah R, Ahmed MS. Source: The Journal of Pharmacology and Experimental Therapeutics. 1995 June; 273(3): 987-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7791132&dopt=Abstract
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Opioids in chronic non-malignant pain. Don't forget methadone for chronic pain. Author(s): Byrne A. Source: Bmj (Clinical Research Ed.). 2001 September 8; 323(7312): 572. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573488&dopt=Abstract
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Optimizing long-term response to methadone maintenance treatment: a 152-week follow-up using higher-dose methadone. Author(s): Maxwell S, Shinderman MS. Source: J Addict Dis. 2002; 21(3): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094996&dopt=Abstract
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Optimizing response to methadone maintenance treatment: use of higher-dose methadone. Author(s): Maxwell S, Shinderman M. Source: J Psychoactive Drugs. 1999 April-June; 31(2): 95-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437990&dopt=Abstract
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Optimizing smoking cessation outcomes among the methadone maintained. Author(s): Frosch DL, Nahom D, Shoptaw S. Source: Journal of Substance Abuse Treatment. 2002 December; 23(4): 425-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495806&dopt=Abstract
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Oral and intravenous methadone use: some clinical and pharmacokinetic aspects. Author(s): Felder C, Uehlinger C, Baumann P, Powell K, Eap CB. Source: Drug and Alcohol Dependence. 1999 June 1; 55(1-2): 137-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10402158&dopt=Abstract
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Oral methadone for managing chronic nonmalignant pain. Author(s): Gardner-Nix JS. Source: Journal of Pain and Symptom Management. 1996 May; 11(5): 321-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8636630&dopt=Abstract
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Oral methadone for the treatment of severe pain in hospitalized children: a report of five cases. Author(s): Shir Y, Shenkman Z, Shavelson V, Davidson EM, Rosen G. Source: The Clinical Journal of Pain. 1998 December; 14(4): 350-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9874015&dopt=Abstract
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Oral premedication in children. A comparison of trimeprazine with a trimeprazine, droperidol and methadone mixture. Author(s): Phillips GH, Mian T, Becker U, Stone PA, Jones HM. Source: Anaesthesia. 1990 October; 45(10): 870-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2240505&dopt=Abstract
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Oral premedication with methadone, promethazine and diclofenac. Author(s): Hyndman J. Source: Anaesthesia and Intensive Care. 1993 April; 21(2): 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8517531&dopt=Abstract
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Organic mood syndrome associated with detoxification from methadone maintenance. Author(s): Kanof PD, Aronson MJ, Ness R. Source: The American Journal of Psychiatry. 1993 March; 150(3): 423-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8434657&dopt=Abstract
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Outbreak of multidrug-resistant tuberculosis at a methadone treatment program. Author(s): Conover C, Ridzon R, Valway S, Schoenstadt L, McAuley J, Onorato I, Paul W. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2001 January; 5(1): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263518&dopt=Abstract
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Outcome after methadone treatment: influence of prior treatment factors and current treatment status. Author(s): Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Source: Drug and Alcohol Dependence. 1994 June; 35(3): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7956752&dopt=Abstract
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Outcome of a second episode of methadone maintenance. Author(s): Calsyn DA, Wells EA, Saxon AJ, Jackson TR, Stanton VV. Source: Drug and Alcohol Dependence. 1996 December 11; 43(3): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9023072&dopt=Abstract
Studies 195
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Outcome of contingency contracting for illicit drug use in a methadone maintenance program. Author(s): Saxon AJ, Calsyn DA, Kivlahan DR, Roszell DK. Source: Drug and Alcohol Dependence. 1993 February; 31(3): 205-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8384984&dopt=Abstract
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Outcomes after methadone maintenance and methadone reduction treatments: twoyear follow-up results from the National Treatment Outcome Research Study. Author(s): Gossop M, Marsden J, Stewart D, Treacy S. Source: Drug and Alcohol Dependence. 2001 May 1; 62(3): 255-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295330&dopt=Abstract
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Outcomes of treatment of socially rehabilitated methadone maintenance patients in physicians' offices (medical maintenance): follow-up at three and a half to nine and a fourth years. Author(s): Novick DM, Joseph H, Salsitz EA, Kalin MF, Keefe JB, Miller EL, Richman BL. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 1994 March; 9(3): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8195910&dopt=Abstract
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Outpatient benzodiazepine detoxification procedure for methadone patients. Author(s): McDuff DR, Schwartz RP, Tommasello A, Tiegel S, Donovan T, Johnson JL. Source: Journal of Substance Abuse Treatment. 1993 May-June; 10(3): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8100281&dopt=Abstract
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Outpatient comparison of buprenorphine and methadone maintenance. I. Effects on opiate use and self-reported adverse effects and withdrawal symptomatology. Author(s): Johnson RE, Fudala PJ, Jaffe JH. Source: Nida Res Monogr. 1991; 105: 585-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876130&dopt=Abstract
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Outpatient comparison of buprenorphine and methadone maintenance. II. Effects on cocaine usage, retention time in study and missed clinic visits. Author(s): Fudala PJ, Johnson RE, Jaffe JH. Source: Nida Res Monogr. 1991; 105: 587-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876131&dopt=Abstract
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Outpatient maintenance/detoxification comparison of methadone and buprenorphine. Author(s): Johnson RE, Fudala PJ, Collins CC, Jaffe JH. Source: Nida Res Monogr. 1989; 95: 384. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2641003&dopt=Abstract
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Outpatient methadone programme for pregnant heroin using women. Author(s): Giles W, Patterson T, Sanders F, Batey R, Thomas D, Collins J. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1989 August; 29(3 Pt 1): 225-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2604651&dopt=Abstract
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Pain responses in methadone-maintained opioid abusers. Author(s): Compton P, Charuvastra VC, Kintaudi K, Ling W. Source: Journal of Pain and Symptom Management. 2000 October; 20(4): 237-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11027904&dopt=Abstract
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Paradoxical activation of major platelet receptors in the methadone-maintained patients after single pill of aspirin. Author(s): Malinin AI, Callahan KP, Serebruany VL. Source: Thrombosis Research. 2001 November 15; 104(4): 297-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728532&dopt=Abstract
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Parent training skills and methadone maintenance: clinical opportunities and challenges. Author(s): Dawe S, Harnett PH, Staiger P, Dadds MR. Source: Drug and Alcohol Dependence. 2000 July 1; 60(1): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821984&dopt=Abstract
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Parental relationships and substance use among methadone patients. The impact on levels of psychological symptomatology. Author(s): Rutherford MJ, Metzger DS, Alterman AI. Source: Journal of Substance Abuse Treatment. 1994 September-October; 11(5): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7869462&dopt=Abstract
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Parenteral methadone: an essential medication for the treatment of pain. Author(s): Manfredi PL, Foley KM, Payne R, Houde R, Inturrisi CE. Source: Journal of Pain and Symptom Management. 2003 August; 26(2): 687-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906950&dopt=Abstract
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Paroxetine increases steady-state concentrations of (R)-methadone in CYP2D6 extensive but not poor metabolizers. Author(s): Begre S, von Bardeleben U, Ladewig D, Jaquet-Rochat S, Cosendai-Savary L, Golay KP, Kosel M, Baumann P, Eap CB. Source: Journal of Clinical Psychopharmacology. 2002 April; 22(2): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910269&dopt=Abstract
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Pathological gambling among methadone patients. Author(s): Feigelman W, Kleinman PH, Lesieur HR, Millman RB, Lesser ML. Source: Drug and Alcohol Dependence. 1995 August; 39(2): 75-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8529535&dopt=Abstract
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Patient outcomes after initiation of Sabbath closure of a methadone maintenance clinic in Israel. Author(s): Gelkopf M, Bleich A, Hayward R, Adelson M. Source: Psychiatric Services (Washington, D.C.). 1998 November; 49(11): 1483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9826253&dopt=Abstract
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Patient perceptions of psychological and physiological withdrawal symptoms and positive factors associated with gradual withdrawal from methadone maintenance treatment: a prospective study. Author(s): Eklund C, Hiltunen AJ, Melin L, Borg S. Source: Substance Use & Misuse. 1997 September; 32(11): 1599-618. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9336869&dopt=Abstract
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Patient retention in mobile and fixed-site methadone maintenance treatment. Author(s): Greenfield L, Brady JV, Besteman KJ, De Smet A. Source: Drug and Alcohol Dependence. 1996 October; 42(2): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8889411&dopt=Abstract
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Patient-controlled analgesia with intravenous L-methadone in a child with cancer pain refractory to high-dose morphine. Author(s): Sabatowski R, Kasper SM, Radbruch L. Source: Journal of Pain and Symptom Management. 2002 January; 23(1): 3-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779660&dopt=Abstract
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Patient-controlled analgesia with oral methadone in cancer pain: preliminary report. Author(s): Mercadante S, Sapio M, Serretta R, Caligara M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1996 August; 7(6): 613-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8879376&dopt=Abstract
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Patterns of alcohol use among methadone clients in a Glasgow housing estate. Author(s): Lowe E, Shewan D. Source: J Psychoactive Drugs. 1999 April-June; 31(2): 145-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437997&dopt=Abstract
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Patterns of drug use in dependent opioid users in methadone treatment. Author(s): Chamberlain N. Source: N Z Med J. 1997 July 11; 110(1047): 258-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9251715&dopt=Abstract
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Patterns of improvement after methadone treatment: 1 year follow-up results from the National Treatment Outcome Research Study. Author(s): Gossop M, Marsden J, Stewart D, Rolfe A. Source: Drug and Alcohol Dependence. 2000 November 1; 60(3): 275-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053762&dopt=Abstract
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Patterns of symptom complaints in methadone maintenance patients. Author(s): Dyer KR, White JM. Source: Addiction (Abingdon, England). 1997 November; 92(11): 1445-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9519488&dopt=Abstract
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Pemoline for the treatment of cocaine dependence in methadone-maintained patients. Author(s): Margolin A, Avants SK, Kosten TR. Source: J Psychoactive Drugs. 1996 July-September; 28(3): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895115&dopt=Abstract
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Perinatal exposure to methadone affects central cholinergic activity in the weanling rat. Author(s): Robinson SE, Mo Q, Maher JR, Wallace MJ, Kunko PM. Source: Drug and Alcohol Dependence. 1996 June; 41(2): 119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8809500&dopt=Abstract
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Personal social networks and HIV status among women on methadone. Author(s): el-Bassel N, Cooper DK, Chen DR, Schilling RF. Source: Aids Care. 1998 December; 10(6): 735-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9924528&dopt=Abstract
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Personality disorders and treatment outcome in methadone maintenance patients. Author(s): Cacciola JS, Rutherford MJ, Alterman AI, McKay JR, Snider EC. Source: The Journal of Nervous and Mental Disease. 1996 April; 184(4): 234-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8604033&dopt=Abstract
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Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users. Author(s): Clarke SM, Mulcahy FM, Tjia J, Reynolds HE, Gibbons SE, Barry MG, Back DJ. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 November 1; 33(9): 1595-7. Epub 2001 September 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568856&dopt=Abstract
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Pharmacokinetics and pharmacodynamics of methadone enantiomers after a single oral dose of racemate. Author(s): Boulton DW, Arnaud P, DeVane CL. Source: Clinical Pharmacology and Therapeutics. 2001 July; 70(1): 48-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452244&dopt=Abstract
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Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts. Author(s): de Vos JW, Geerlings PJ, van den Brink W, Ufkes JG, van Wilgenburg H. Source: European Journal of Clinical Pharmacology. 1995; 48(5): 361-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8641323&dopt=Abstract
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Pharmacokinetics of methadone in HIV-positive patients receiving the nonnucleoside reverse transcriptase efavirenz. Author(s): Calvo R, Lukas JC, Rodriguez M, Carlos MA, Suarez E. Source: British Journal of Clinical Pharmacology. 2002 February; 53(2): 212-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851649&dopt=Abstract
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Physicians' attitudes and retention of patients in their methadone maintenance programs. Author(s): Caplehorn JR, Irwig L, Saunders JB. Source: Substance Use & Misuse. 1996 May; 31(6): 663-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8816115&dopt=Abstract
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Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain. Author(s): Moryl N, Santiago-Palma J, Kornick C, Derby S, Fischberg D, Payne R, Manfredi PL. Source: Pain. 2002 April; 96(3): 325-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973005&dopt=Abstract
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Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment. Author(s): Eap CB, Bourquin M, Martin J, Spagnoli J, Livoti S, Powell K, Baumann P, Deglon J. Source: Drug and Alcohol Dependence. 2000 December 22; 61(1): 47-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064183&dopt=Abstract
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Plasma methadone concentrations as an indicator of opioid withdrawal symptoms and heroin use in a methadone maintenance program. Author(s): Torrens M, Castillo C, San L, del Moral E, Gonzalez ML, de la Torre R. Source: Drug and Alcohol Dependence. 1998 November 1; 52(3): 193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839145&dopt=Abstract
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Plasma methadone monitoring with methadone maintenance treatment. Author(s): Wolff K, Hay AW. Source: Drug and Alcohol Dependence. 1994 August; 36(1): 69-71; Author Reply 73-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7988362&dopt=Abstract
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Politics, cancer pain, and methadone. Author(s): Baumrucker SJ. Source: Am J Hosp Palliat Care. 2000 May-June; 17(3): 153-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886064&dopt=Abstract
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Population-based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility. Author(s): Wolff K, Rostami-Hodjegan A, Hay AW, Raistrick D, Tucker G. Source: Addiction (Abingdon, England). 2000 December; 95(12): 1771-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11177493&dopt=Abstract
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Post-traumatic stress disorder among inner city methadone maintenance patients. Author(s): Villagomez RE, Meyer TJ, Lin MM, Brown LS Jr. Source: Journal of Substance Abuse Treatment. 1995 July-August; 12(4): 253-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8830152&dopt=Abstract
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Posttraumatic stress disorder and short-term outcome in early methadone treatment. Author(s): Hien DA, Nunes E, Levin FR, Fraser D. Source: Journal of Substance Abuse Treatment. 2000 July; 19(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867298&dopt=Abstract
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Pre- and in-treatment predictors of retention in methadone treatment using survival analysis. Author(s): Magura S, Nwakeze PC, Demsky SY. Source: Addiction (Abingdon, England). 1998 January; 93(1): 51-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624711&dopt=Abstract
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Prediction of 7 months methadone maintenance treatment response by four measures of antisociality. Author(s): Alterman AI, Rutherford MJ, Cacciola JS, McKay JR, Boardman CR. Source: Drug and Alcohol Dependence. 1998 February 1; 49(3): 217-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9571386&dopt=Abstract
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Predictive validity of the Addiction Severity Index's composite scores in the assessment of 2-year outcomes in a methadone maintenance population. Author(s): Bovasso GB, Alterman AI, Cacciola JS, Cook TG. Source: Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors. 2001 September; 15(3): 171-6. Erratum In: Psychol Addict Behav 2002 March; 16(1): 71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563793&dopt=Abstract
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Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients. Author(s): Backmund M, Meyer K, Eichenlaub D, Schutz CG. Source: Drug and Alcohol Dependence. 2001 October 1; 64(2): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11543987&dopt=Abstract
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Predictors of injecting and injecting risk-taking behaviour among methadonemaintenance clients. Author(s): Darke S, Swift W, Hall W, Ross M. Source: Addiction (Abingdon, England). 1994 March; 89(3): 311-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8173500&dopt=Abstract
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Predictors of nonadherence to HIV-related medication regimens during methadone stabilization. Author(s): Avants SK, Margolin A, Warburton LA, Hawkins KA, Shi J. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2001 Winter; 10(1): 69-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268829&dopt=Abstract
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Predictors of outcome in methadone programs: effect of HIV counseling and testing. Author(s): Farley TA, Cartter ML, Wassell JT, Hadler JL. Source: Conn Med. 1994 March; 58(3): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8039381&dopt=Abstract
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Predictors of patient retention in a newly established methadone maintenance treatment programme. Author(s): del Rio M, Mino A, Perneger TV. Source: Addiction (Abingdon, England). 1997 October; 92(10): 1353-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9489052&dopt=Abstract
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Prenatal diagnosis of amniotic band syndrome in a methadone user: review of the literature and a case report. Author(s): Daly CA, Freeman J, Weston W, Kovar I, Phelan M. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1996 August; 8(2): 123-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883316&dopt=Abstract
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Prenatal methadone exposure: effects on behavior in early infancy. Author(s): Johnson HL, Rosen TS. Source: Pediatr Pharmacol (New York). 1982; 2(2): 113-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760403&dopt=Abstract
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Prescribing injectable and oral methadone to opiate addicts: results from the 1995 national postal survey of community pharmacies in England and Wales. Author(s): Strang J, Sheridan J, Barber N. Source: Bmj (Clinical Research Ed.). 1996 August 3; 313(7052): 270-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8704540&dopt=Abstract
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Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities. Author(s): Rosenblum A, Joseph H, Fong C, Kipnis S, Cleland C, Portenoy RK. Source: Jama : the Journal of the American Medical Association. 2003 May 14; 289(18): 2370-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746360&dopt=Abstract
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Prevalence and correlates of intravenous methadone syrup administration in Adelaide, Australia. Author(s): Humeniuk R, Ali R, McGregor C, Darke S. Source: Addiction (Abingdon, England). 2003 April; 98(4): 413-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653811&dopt=Abstract
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Prevalence and incidence rate of HIV, hepatitis B and C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995. Author(s): Broers B, Junet C, Bourquin M, Deglon JJ, Perrin L, Hirschel B. Source: Aids (London, England). 1998 October 22; 12(15): 2059-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9814875&dopt=Abstract
Studies 203
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Prevalence of hepatitis B and C infection in a methadone clinic population: implications for hepatitis B vaccination. Author(s): Carter H, Robinson G, Hanlon C, Hailwood C, Massarotto A. Source: N Z Med J. 2001 July 27; 114(1136): 324-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548096&dopt=Abstract
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Prevalence of psychiatric disorder in a methadone maintenance population. Author(s): Callaly T, Trauer T, Munro L, Whelan G. Source: The Australian and New Zealand Journal of Psychiatry. 2001 October; 35(5): 6015. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11551274&dopt=Abstract
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Prevalence, severity and correlates of psychological morbidity among methadone maintenance clients. Author(s): Darke S, Swift W, Hall W. Source: Addiction (Abingdon, England). 1994 February; 89(2): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8173487&dopt=Abstract
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Prevalence, symptoms and correlates of antisocial personality disorder among methadone maintenance clients. Author(s): Darke S, Hall W, Swift W. Source: Drug and Alcohol Dependence. 1994 February; 34(3): 253-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8033764&dopt=Abstract
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Previous participation in outpatient methadone program and residential treatment outcome: a research note from Hong Kong. Author(s): Cheung YW, Ch'ien JM. Source: Substance Use & Misuse. 1999 January; 34(1): 103-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10052393&dopt=Abstract
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Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone. Author(s): Howells C, Allen S, Gupta J, Stillwell G, Marsden J, Farrell M. Source: Drug and Alcohol Dependence. 2002 July 1; 67(2): 169-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095666&dopt=Abstract
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Prisoner settles case for right to start methadone in prison. Author(s): Cochrane Database Syst Rev. 2002;(2):CD003409 Source: Can Hiv Aids Policy Law Newsl. 1999 Fall-1999 Winter; 5(1): 34-5, 42. English, French. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12076479
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Probable metabolic interaction between methadone and fluvoxamine in addict patients. Author(s): Bertschy G, Baumann P, Eap CB, Baettig D. Source: Therapeutic Drug Monitoring. 1994 February; 16(1): 42-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8160253&dopt=Abstract
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Prognostic factors in Buprenorphine- versus methadone-maintained patients. Author(s): Schottenfeld RS, Pakes JR, Kosten TR. Source: The Journal of Nervous and Mental Disease. 1998 January; 186(1): 35-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9457145&dopt=Abstract
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Program quality effects on patient outcomes during methadone maintenance: a study of 17 clinics. Author(s): Magura S, Nwakeze PC, Kang SY, Demsky S. Source: Substance Use & Misuse. 1999 July; 34(9): 1299-324. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10419225&dopt=Abstract
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Prohibition of take-home dosages: negative consequences on methadone maintenance treatment. Author(s): Pani PP, Pirastu R, Ricci A, Gessa GL. Source: Drug and Alcohol Dependence. 1996 May; 41(1): 81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793314&dopt=Abstract
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Providing medical care to methadone clinic patients: referral vs on-site care. Author(s): Umbricht-Schneiter A, Ginn DH, Pabst KM, Bigelow GE. Source: American Journal of Public Health. 1994 February; 84(2): 207-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8296941&dopt=Abstract
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Provision of methadone treatment in primary care medical practices: review of the Scottish experience and implications for US policy. Author(s): Weinrich M, Stuart M. Source: Jama : the Journal of the American Medical Association. 2000 March 8; 283(10): 1343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714738&dopt=Abstract
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Psychiatric comorbidity: prevalence in methadone maintenance treatment. Author(s): Milby JB, Sims MK, Khuder S, Schumacher JE, Huggins N, McLellan AT, Woody G, Haas N. Source: The American Journal of Drug and Alcohol Abuse. 1996 February; 22(1): 95-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8651147&dopt=Abstract
Studies 205
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Psychiatric severity and treatment response in a comprehensive methadone maintenance treatment program. Author(s): Pani PP, Trogu E, Contu P, Agus A, Gessa GL. Source: Drug and Alcohol Dependence. 1997 November 25; 48(2): 119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9363411&dopt=Abstract
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Psychosis in a methadone-substituted patient during interferon-alpha treatment of hepatitis C. Author(s): Schafer M, Boetsch T, Laakmann G. Source: Addiction (Abingdon, England). 2000 July; 95(7): 1101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962774&dopt=Abstract
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Psychotherapy in community methadone programs: a validation study. Author(s): Woody GE, McLellan AT, Luborsky L, O'Brien CP. Source: The American Journal of Psychiatry. 1995 September; 152(9): 1302-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7653685&dopt=Abstract
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Quality improvement for methadone maintenance treatment. Author(s): Bell J. Source: Substance Use & Misuse. 2000 October-December; 35(12-14): 1735-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11138706&dopt=Abstract
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Quantitative analysis of methadone and two major metabolites in hair by positive chemical ionization ion trap mass spectrometry. Author(s): Wilkins DG, Nagasawa PR, Gygi SP, Foltz RL, Rollins DE. Source: Journal of Analytical Toxicology. 1996 October; 20(6): 355-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8889670&dopt=Abstract
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Quantitative liquid chromatographic thermospray-tandem mass spectrometric analysis of some analgesics and tranquilizers of the methadone, butyrophenone, or diphenylbutylpiperidine groups in whole blood. Author(s): Verweij AM, Hordijk ML, Lipman PJ. Source: Journal of Analytical Toxicology. 1995 March-April; 19(2): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7769788&dopt=Abstract
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Quantitative urine drug monitoring in methadone programs: potential clinical uses. Author(s): McCarthy J. Source: J Psychoactive Drugs. 1994 April-June; 26(2): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7931864&dopt=Abstract
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Radioimmunoassay of drugs of abuse in hair. Part 1: Methadone in human hair, method adaptation and the evaluation of decontamination procedures. Author(s): Marsh A, Evans MB. Source: Journal of Pharmaceutical and Biomedical Analysis. 1994 September; 12(9): 112330. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7803562&dopt=Abstract
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Radioimmunoassay of drugs of abuse in hair. Part 2: The determination of methadone in the hair of known drug users. Author(s): Marsh A, Evans MB, Strang J. Source: Journal of Pharmaceutical and Biomedical Analysis. 1995 June; 13(7): 829-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8562606&dopt=Abstract
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Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal. Author(s): Bearn J, Gossop M, Strang J. Source: Drug and Alcohol Dependence. 1996 December 2; 43(1-2): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8957147&dopt=Abstract
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Randomized trial of supervised injectable versus oral methadone maintenance: report of feasibility and 6-month outcome. Author(s): Strang J, Marsden J, Cummins M, Farrell M, Finch E, Gossop M, Stewart D, Welch S. Source: Addiction (Abingdon, England). 2000 November; 95(11): 1631-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219367&dopt=Abstract
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Rapid admission and retention on methadone. Author(s): Maddux JF, Desmond DP, Esquivel M. Source: The American Journal of Drug and Alcohol Abuse. 1995 November; 21(4): 53347. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8561101&dopt=Abstract
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Rapid cortical hemoglobin deoxygenation after heroin and methadone injection in humans: a preliminary report. Author(s): Stohler R, Dursteler KM, Stormer R, Seifritz E, Hug I, Sattler-Mayr J, MullerSpahn F, Ladewig D, Hock C. Source: Drug and Alcohol Dependence. 1999 November 1; 57(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617310&dopt=Abstract
Studies 207
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Rapid determination of methadone and its major metabolite in biological fluids by gas-liquid chromatography with thermionic detection for maintenance treatment of opiate addicts. Author(s): Chikhi-Chorfi N, Pham-Huy C, Galons H, Manuel N, Lowenstein W, Warnet JM, Claude JR. Source: J Chromatogr B Biomed Sci Appl. 1998 November 6; 718(2): 278-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9840439&dopt=Abstract
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Rapid determination of methadone in plasma, cerebrospinal fluid, and urine by gas chromatography and its application to routine drug monitoring. Author(s): Schmidt N, Sittl R, Brune K, Geisslinger G. Source: Pharmaceutical Research. 1993 March; 10(3): 441-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8464820&dopt=Abstract
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Rapid measurement of plasma methadone in a clinical setting using florescence polarization immunoassay. Author(s): Kell MJ, Techman T. Source: J Addict Dis. 1996; 15(2): 69-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8704002&dopt=Abstract
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Rapid switching from morphine to methadone in cancer patients with poor response to morphine. Author(s): Mercadante S, Casuccio A, Calderone L. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 October; 17(10): 3307-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10506634&dopt=Abstract
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Rapid transition from methadone maintenance to naltrexone. Author(s): Loimer N, Lenz K, Presslich O, Schmid R. Source: Lancet. 1990 January 13; 335(8681): 111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1967391&dopt=Abstract
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Rated well-being in relation to plasma concentrations of l- and d-methadone in satisfied and dissatisfied patients on methadone maintenance treatment. Author(s): Hiltunen AJ, Beck O, Hjemdahl P, Liljeberg P, Almstrom U, Brodin K, von Wachenfeldt J, Borg S. Source: Psychopharmacology. 1999 April; 143(4): 385-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367556&dopt=Abstract
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Reactions of methadone patients to HIV antibody testing. Author(s): Magura S, Shapiro JL, Grossman JI, Siddiqi Q, Lipton DS, Amann KR, Koger J, Gehan K. Source: Adv Alcohol Subst Abuse. 1990; 8(3-4): 97-111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2343800&dopt=Abstract
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Reasons for discharge from methadone maintenance for addicts at high risk of HIV infection or transmission. Author(s): Grella CE, Anglin MD, Wugalter SE, Rawson R, Hasson A. Source: J Psychoactive Drugs. 1994 April-June; 26(2): 223-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7931867&dopt=Abstract
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Recreational drugs, methadone and protease inhibitors. Author(s): Timour K. Source: Body Posit. 1998 April-May; 11(4-5): 34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11365255&dopt=Abstract
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Rectal methadone in cancer patients with pain. A preliminary clinical and pharmacokinetic study. Author(s): Ripamonti C, Zecca E, Brunelli C, Rizzio E, Saita L, Lodi F, De Conno F. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1995 October; 6(8): 841-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8589026&dopt=Abstract
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Reducing HIV risk behavior among injection drug users: effect of methadone maintenance treatment on number of sex partners. Author(s): Longshore D, Hsieh SC, Anglin MD. Source: Int J Addict. 1994 April; 29(6): 741-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8034383&dopt=Abstract
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Reducing illicit drug use among methadone patients. Author(s): Stitzer ML, Kirby KC. Source: Nida Res Monogr. 1991; 106: 178-203. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1922287&dopt=Abstract
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Reducing the risk of AIDS through methadone maintenance treatment. Author(s): Ball JC, Lange WR, Myers CP, Friedman SR. Source: Journal of Health and Social Behavior. 1988 September; 29(3): 214-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3241064&dopt=Abstract
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Reduction in constipation and laxative requirements following opioid rotation to methadone: a report of four cases. Author(s): Daeninck PJ, Bruera E. Source: Journal of Pain and Symptom Management. 1999 October; 18(4): 303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534971&dopt=Abstract
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Reduction of AIDS risk among 41 heroin addicted female street prostitutes: effects of free methadone maintenance. Author(s): Bellis DJ. Source: J Addict Dis. 1993; 12(1): 7-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8381030&dopt=Abstract
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Reduction of opiate withdrawal-like symptoms by cocaine abuse during methadone and buprenorphine maintenance. Author(s): Stine SM, Kosten TR. Source: The American Journal of Drug and Alcohol Abuse. 1994 November; 20(4): 44558. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7832179&dopt=Abstract
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Regulating controversial programs for unpopular people: methadone maintenance and syringe exchange programs. Author(s): Des Jarlais DC, Paone D, Friedman SR, Peyser N, Newman RG. Source: American Journal of Public Health. 1995 November; 85(11): 1577-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485676&dopt=Abstract
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Relationship between LAAM-methadone preference and treatment outcomes. Author(s): White JM, Danz C, Kneebone J, La Vincente SF, Newcombe DA, Ali RL. Source: Drug and Alcohol Dependence. 2002 May 1; 66(3): 295-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062464&dopt=Abstract
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Relationship between maternal methadone dosage and neonatal withdrawal. Author(s): Dashe JS, Sheffield JS, Olscher DA, Todd SJ, Jackson GL, Wendel GD. Source: Obstetrics and Gynecology. 2002 December; 100(6): 1244-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468169&dopt=Abstract
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Relationship between maternal methadone dosage, maternal-neonatal methadone levels, and neonatal withdrawal. Author(s): Doberczak TM, Kandall SR, Friedmann P. Source: Obstetrics and Gynecology. 1993 June; 81(6): 936-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8497359&dopt=Abstract
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Relationship between problem gambling and substance use in a methadone maintenance population. Author(s): Ledgerwood DM, Downey KK. Source: Addictive Behaviors. 2002 July-August; 27(4): 483-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188587&dopt=Abstract
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Relationship of HIV testing and high-risk behaviors among clients in methadone maintenance treatment. Author(s): Grella CE, Campos M, Anglin MD. Source: Aids Education and Prevention : Official Publication of the International Society for Aids Education. 1998 October; 10(5): 403-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799937&dopt=Abstract
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Relationships between childhood abuse and neglect experience and HIV risk behaviors among methadone treatment drop-outs. Author(s): Kang SY, Deren S, Goldstein MF. Source: Child Abuse & Neglect. 2002 December; 26(12): 1275-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464301&dopt=Abstract
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Relationships of personality disorders with problem severity in methadone patients. Author(s): Rutherford MJ, Cacciola JS, Alterman AI. Source: Drug and Alcohol Dependence. 1994 March; 35(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8082558&dopt=Abstract
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Relative abuse liability of benzodiazepines in methadone maintained populations in three cities. Author(s): Iguchi MY, Griffiths RR, Bickel WK, Handelsman L, Childress AR, McLellan AT. Source: Nida Res Monogr. 1989; 95: 364-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2577040&dopt=Abstract
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Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets. Author(s): Christrup LL, Angelo HR, Bonde J, Kristensen F, Rasmussen SN. Source: Acta Pharm Nord. 1990; 2(2): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2354033&dopt=Abstract
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Relative potency of levo-alpha-acetylmethadol and methadone in humans under acute dosing conditions. Author(s): Eissenberg T, Stitzer ML, Bigelow GE, Buchhalter AR, Walsh SL. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 May; 289(2): 936-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215673&dopt=Abstract
Studies 211
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Reliability and validity of 6-month timeline reports of cocaine and heroin use in a methadone population. Author(s): Ehrman RN, Robbins SJ. Source: Journal of Consulting and Clinical Psychology. 1994 August; 62(4): 843-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7962889&dopt=Abstract
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Replacement of (R)-methadone by a double dose of (R,S)-methadone in addicts: interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics. Author(s): Eap CB, Finkbeiner T, Gastpar M, Scherbaum N, Powell K, Baumann P. Source: European Journal of Clinical Pharmacology. 1996; 50(5): 385-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8839661&dopt=Abstract
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Report of the Council on Scientific Affairs: methadone maintenance and needleexchange programs to reduce the medical and public health consequences of drug abuse. Author(s): Yoast R, Williams MA, Deitchman SD, Champion HC. Source: J Addict Dis. 2001; 20(2): 15-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318395&dopt=Abstract
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Reporting of HIV risk behaviors by injection drug using heterosexual couples in methadone maintenance. Author(s): Wells EA, Clark LL, Calsyn DA, Saxon AJ, Jackson TR, Wrede AF. Source: Drug and Alcohol Dependence. 1994 August; 36(1): 33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7988357&dopt=Abstract
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Respiratory depression during methadone rotation in a patient with advanced cancer. Author(s): Oneschuk D, Bruera E. Source: Journal of Palliative Care. 2000 Summer; 16(2): 50-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10887733&dopt=Abstract
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Respiratory depression in a patient receiving oral methadone for cancer pain. Author(s): Hunt G, Bruera E. Source: Journal of Pain and Symptom Management. 1995 July; 10(5): 401-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7673774&dopt=Abstract
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Response to a report on false-positive results in a methadone enzyme immunoassay. Author(s): Tsay YG, Khosropour P. Source: Clinical Chemistry. 1998 October; 44(10): 2221-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9761270&dopt=Abstract
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Response to methadone maintenance and counseling in antisocial patients with and without major depression. Author(s): Alterman AI, Rutherford MJ, Cacciola JS, McKay JR, Woody GE. Source: The Journal of Nervous and Mental Disease. 1996 November; 184(11): 695-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8955683&dopt=Abstract
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Retention in a low-threshold methadone maintenance program. Author(s): Torrens M, Castillo C, Perez-Sola V. Source: Drug and Alcohol Dependence. 1996 May; 41(1): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793310&dopt=Abstract
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Retention in methadone maintenance and heroin addicts' risk of death. Author(s): Caplehorn JR, Dalton MS, Cluff MC, Petrenas AM. Source: Addiction (Abingdon, England). 1994 February; 89(2): 203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8173486&dopt=Abstract
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Retention in methadone maintenance is associated with reductions in different HIV risk behaviors for women and men. Author(s): Wells EA, Calsyn DA, Clark LL, Saxon AJ, Jackson TR. Source: The American Journal of Drug and Alcohol Abuse. 1996 November; 22(4): 50921. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8911589&dopt=Abstract
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Retention in methadone maintenance treatment programs, Connecticut and Massachusetts, 1990-1993. Author(s): MacGowan RJ, Swanson NM, Brackbill RM, Rugg DL, Barker T, Molde S. Source: J Psychoactive Drugs. 1996 July-September; 28(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895111&dopt=Abstract
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Retention in treatment of heroin users in Italy: the role of treatment type and of methadone maintenance dosage. Author(s): D'Ippoliti D, Davoli M, Perucci CA, Pasqualini F, Bargagli AM. Source: Drug and Alcohol Dependence. 1998 October 1; 52(2): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9800146&dopt=Abstract
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Retention of patients who entered methadone maintenance via an interim methadone clinic. Author(s): Friedman P, Des Jarlais DC, Peyser NP, Nichols SE, Drew E, Newman RG. Source: J Psychoactive Drugs. 1994 April-June; 26(2): 217-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7931866&dopt=Abstract
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Retention rate and illicit opioid use during methadone maintenance interventions: a meta-analysis. Author(s): Farre M, Mas A, Torrens M, Moreno V, Cami J. Source: Drug and Alcohol Dependence. 2002 February 1; 65(3): 283-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11841899&dopt=Abstract
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Retention, HIV risk, and illicit drug use during treatment: methadone dose and visit frequency. Author(s): Rhoades HM, Creson D, Elk R, Schmitz J, Grabowski J. Source: American Journal of Public Health. 1998 January; 88(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9584030&dopt=Abstract
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Retrospective analyses of additional services for methadone maintenance patients. Author(s): Abbott PJ, Moore B, Delaney H, Weller S. Source: Journal of Substance Abuse Treatment. 1999 July-September; 17(1-2): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435261&dopt=Abstract
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Reversible delirium during opiod switching from transdermal fentanyl to methadone. Author(s): del Rosario MA, Feria M, Martin AS, Ortega JJ, del Castillo LP. Source: Journal of Pain and Symptom Management. 2001 March; 21(3): 177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303498&dopt=Abstract
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Revisiting the effectiveness of methadone treatment on crime reductions in the 1990s. Author(s): Rothbard A, Alterman A, Rutherford M, Liu F, Zelinski S, McKay J. Source: Journal of Substance Abuse Treatment. 1999 June; 16(4): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10349606&dopt=Abstract
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Rhabdomyolysis and acute renal failure following methadone abuse. Author(s): Hojs R, Sinkovic A. Source: Nephron. 1992; 62(3): 362. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1436354&dopt=Abstract
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Rifampin-induced methadone withdrawal in AIDS. Author(s): Holmes VF. Source: Journal of Clinical Psychopharmacology. 1990 December; 10(6): 443-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2286719&dopt=Abstract
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Risk behaviour for HIV transmission in attenders on methadone maintenance. Author(s): Williams H, Mullan E, O'Connor JJ, Kinsella A. Source: Ir J Med Sci. 1990 May; 159(5): 141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2397983&dopt=Abstract
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Risk characteristics associated with chronic unemployment in methadone clients. Author(s): Hermalin JA, Steer RA, Platt JJ, Metzger DS. Source: Drug and Alcohol Dependence. 1990 October; 26(2): 117-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2242713&dopt=Abstract
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Risk factors associated with noncompliance with methadone substitution therapy (MST) and relapse among chronic opiate users in an Outer London community. Author(s): Mutasa HC. Source: Journal of Advanced Nursing. 2001 July; 35(1): 97-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442687&dopt=Abstract
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Risk factors for needle sharing among methadone-treated patients. Author(s): Metzger D, Woody G, De Philippis D, McLellan AT, O'Brien CP, Platt JJ. Source: The American Journal of Psychiatry. 1991 May; 148(5): 636-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2018166&dopt=Abstract
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Role of methadone in the management of pain in cancer patients. Author(s): Bruera E, Neumann CM. Source: Oncology (Huntingt). 1999 September; 13(9): 1275-82; Discussion 1285-8, 1291. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10509323&dopt=Abstract
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Safer sex strategies for women: the hierarchical model in methadone treatment clinics. Author(s): Stein Z, Saez H, el-Sadr W, Healton C, Mannheimer S, Messeri P, Scimeca MM, Van Devanter N, Zimmerman R, Betne P. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 1999 March; 76(1): 62-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10091191&dopt=Abstract
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Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: a prospective study in methadone, heroin, codeine and morphine addicts. Author(s): Hensel M, Kox WJ. Source: Acta Anaesthesiologica Scandinavica. 2000 March; 44(3): 326-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714849&dopt=Abstract
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Saliva/plasma ratio of methadone and EDDP. Author(s): Bermejo AM, Lucas AC, Tabernero MJ. Source: Journal of Analytical Toxicology. 2000 January-February; 24(1): 70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10654573&dopt=Abstract
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Screening and treatment of tuberculosis in a methadone maintenance treatment program. Author(s): Lee HK, Bluestone H, Frances R. Source: Hosp Community Psychiatry. 1994 August; 45(8): 759-60, 764. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7982689&dopt=Abstract
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Screening for drugs of abuse (II): Cannabinoids, lysergic acid diethylamide, buprenorphine, methadone, barbiturates, benzodiazepines and other drugs. Author(s): Simpson D, Braithwaite RA, Jarvie DR, Stewart MJ, Walker S, Watson IW, Widdop B. Source: Annals of Clinical Biochemistry. 1997 September; 34 ( Pt 5): 460-510. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9293303&dopt=Abstract
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Screening for urinary methadone by capillary electrophoretic immunoassays and confirmation by capillary electrophoresis-mass spectrometry. Author(s): Thormann W, Lanz M, Caslavska J, Siegenthaler P, Portmann R. Source: Electrophoresis. 1998 January; 19(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9511863&dopt=Abstract
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Selected in-treatment outcomes of long-term methadone maintenance treatment patients in New York State. Author(s): Appel PW, Joseph H, Kott A, Nottingham W, Tasiny E, Habel E. Source: The Mount Sinai Journal of Medicine, New York. 2001 January; 68(1): 55-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135507&dopt=Abstract
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Selective antibodies to methadone enantiomers: synthesis of (R)- and (R,S)methadone conjugates and determination by an immunoenzymatic method in human serum. Author(s): Chikhi-Chorfi N, Galons H, Pham-Huy C, Thevenin M, Warnet JM, Claude JR. Source: Chirality. 2001 May 5; 13(4): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284023&dopt=Abstract
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Self-efficacy and illicit opioid use in a 180-day methadone detoxification treatment. Author(s): Reilly PM, Sees KL, Shopshire MS, Hall SM, Delucchi KL, Tusel DJ, Banys P, Clark HW, Piotrowski NA. Source: Journal of Consulting and Clinical Psychology. 1995 February; 63(1): 158-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7896984&dopt=Abstract
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Sensitivity to acute methadone dose changes in maintenance patients. Author(s): Robles E, Gilmore-Thomas KK, Miller FB, McMillan DE. Source: Journal of Substance Abuse Treatment. 2002 December; 23(4): 409-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495803&dopt=Abstract
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Serum methadone concentrations. Author(s): Sellman D, Sharma J. Source: N Z Med J. 1993 July 28; 106(960): 319. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8341466&dopt=Abstract
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Services provided during methadone treatment. A gender comparison. Author(s): Rowan-Szal GA, Chatham LR, Joe GW, Simpson DD. Source: Journal of Substance Abuse Treatment. 2000 July; 19(1): 7-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867295&dopt=Abstract
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Sex trading and psychological distress among women on methadone. Author(s): El-Bassel N, Simoni JM, Cooper DK, Gilbert L, Schilling RF. Source: Psychology of Addictive Behaviors : Journal of the Society of Psychologists in Addictive Behaviors. 2001 September; 15(3): 177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563794&dopt=Abstract
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Sex, drugs, and HIV: does methadone maintenance reduce drug use and risky sexual behavior? Author(s): Lollis CM, Strothers HS, Chitwood DD, McGhee M. Source: Journal of Behavioral Medicine. 2000 December; 23(6): 545-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199087&dopt=Abstract
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Sexual abuse among women entering methadone treatment. Author(s): Bartholomew NG, Rowan-Szal GA, Chatham LR, Nucatola DC, Simpson DD. Source: J Psychoactive Drugs. 2002 October-December; 34(4): 347-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562102&dopt=Abstract
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Sexual dysfunction and psychological distress in methadone maintenance. Author(s): Spring WD Jr, Willenbring ML, Maddux TL. Source: Int J Addict. 1992 November; 27(11): 1325-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1446965&dopt=Abstract
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Shorter dosing interval of opiate solution shortens hospital stay for methadone babies. Author(s): Jones HC. Source: Family Medicine. 1999 May; 31(5): 327-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10407710&dopt=Abstract
Studies 217
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Short-term methadone administration reduces alcohol consumption in non-alcoholic heroin addicts. Author(s): Caputo F, Addolorato G, Domenicali M, Mosti A, Viaggi M, Trevisani F, Gasbarrini G, Bernardi M, Stefanini GF; Services for Addiction Treatment. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 2002 March-April; 37(2): 164-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912072&dopt=Abstract
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Simultaneous determination of drugs of abuse (opiates, cocaine and amphetamine) in human hair by GC/MS and its application to a methadone treatment program. Author(s): Moeller MR, Fey P, Wennig R. Source: Forensic Science International. 1993 December; 63(1-3): 185-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8138220&dopt=Abstract
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Site dependence of postmortem blood methadone concentrations. Author(s): Levine B, Wu SC, Dixon A, Smialek JE. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1995 June; 16(2): 97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7572883&dopt=Abstract
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Sleep-disordered breathing in stable methadone programme patients: a pilot study. Author(s): Teichtahl H, Prodromidis A, Miller B, Cherry G, Kronborg I. Source: Addiction (Abingdon, England). 2001 March; 96(3): 395-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255580&dopt=Abstract
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Slow metabolism and long half life of methadone in a patient with lung cancer and cirrhosis. Author(s): Beauverie P, Furlan V, Edel YA. Source: Annales De Medecine Interne. 2001 November; 152 Suppl 7: 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965098&dopt=Abstract
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Slow-release morphine was not more effective than methadone in reducing neonatal abstinence syndrome. Author(s): Lee TS. Source: The Western Journal of Medicine. 2000 January; 172(1): 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695439&dopt=Abstract
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Smoking cessation in methadone maintenance. Author(s): Shoptaw S, Rotheram-Fuller E, Yang X, Frosch D, Nahom D, Jarvik ME, Rawson RA, Ling W. Source: Addiction (Abingdon, England). 2002 October; 97(10): 1317-28; Discussion 1325. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359036&dopt=Abstract
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Smoking during pregnancy and intention to quit: a profile of methadone-maintained women. Author(s): Haug NA, Stitzer ML, Svikis DS. Source: Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. 2001 November; 3(4): 333-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694200&dopt=Abstract
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Social relationships and intravenous drug use among methadone maintenance patients. Author(s): Gogineni A, Stein MD, Friedmann PD. Source: Drug and Alcohol Dependence. 2001 September 1; 64(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470340&dopt=Abstract
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Solid-phase microextraction for the determination of pethidine and methadone in human urine using gas chromatography with nitrogen-phosphorus detection. Author(s): Myung SW, Kim S, Park JH, Kim M, Lee JC, Kim TJ. Source: The Analyst. 1999 September; 124(9): 1283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10736851&dopt=Abstract
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Solid-phase microextraction in the determination of methadone in human saliva by gas chromatography-mass spectrometry. Author(s): dos Santos Lucas AC, Bermejo A, Fernandez P, Tabernero MJ. Source: Journal of Analytical Toxicology. 2000 March; 24(2): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732946&dopt=Abstract
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Stages and processes of change among polydrug users in methadone maintenance treatment. Author(s): Belding MA, Iguchi MY, Lamb RJ, Lakin M, Terry R. Source: Drug and Alcohol Dependence. 1995 July; 39(1): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7587974&dopt=Abstract
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Status report from the American Methadone Treatment Association. Author(s): Parrino MW. Source: J Psychoactive Drugs. 1994 April-June; 26(2): 117-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7931855&dopt=Abstract
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Steady-state pharmacokinetics and pharmacodynamics in methadone maintenance patients: comparison of those who do and do not experience withdrawal and concentration-effect relationships. Author(s): Dyer KR, Foster DJ, White JM, Somogyi AA, Menelaou A, Bochner F. Source: Clinical Pharmacology and Therapeutics. 1999 June; 65(6): 685-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10391674&dopt=Abstract
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Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients. Author(s): Foster DJ, Somogyi AA, Dyer KR, White JM, Bochner F. Source: British Journal of Clinical Pharmacology. 2000 November; 50(5): 427-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069437&dopt=Abstract
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Steady-state pharmacokinetics of methadone in opioid addicts. Author(s): Wolff K, Hay AW, Raistrick D, Calvert R. Source: European Journal of Clinical Pharmacology. 1993; 44(2): 189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8453965&dopt=Abstract
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Stereoselective determination of methadone in serum by HPLC following solid-phase extraction on disk. Author(s): Rudaz S, Veuthey JL. Source: Journal of Pharmaceutical and Biomedical Analysis. 1996 June; 14(8-10): 1271-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8818045&dopt=Abstract
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Stereoselective pharmacokinetics of methadone in chronic pain patients. Author(s): Kristensen K, Blemmer T, Angelo HR, Christrup LL, Drenck NE, Rasmussen SN, Sjogren P. Source: Therapeutic Drug Monitoring. 1996 June; 18(3): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8738759&dopt=Abstract
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Stereoselective quantification of methadone and its major oxidative metabolite, 2ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, in human urine using highperformance liquid chromatography. Author(s): Foster DJ, Somogyi AA, Bochner F. Source: J Chromatogr B Biomed Sci Appl. 2000 July 7; 744(1): 165-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10985578&dopt=Abstract
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Stereoselective screening for and confirmation of urinary enantiomers of amphetamine, methamphetamine, designer drugs, methadone and selected metabolites by capillary electrophoresis. Author(s): Ramseier A, Caslavska J, Thormann W. Source: Electrophoresis. 1999 September; 20(13): 2726-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10532341&dopt=Abstract
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Storing methadone in babies' bottles puts young children at risk. Author(s): Harkin K, Quinn C, Bradley F. Source: Bmj (Clinical Research Ed.). 1999 January 30; 318(7179): 329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9924072&dopt=Abstract
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Strategies for increasing retention in methadone programs. Author(s): Condelli WS. Source: J Psychoactive Drugs. 1993 April-June; 25(2): 143-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8377082&dopt=Abstract
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Street-level drug law enforcement and entry into methadone maintenance treatment. Author(s): Weatherburn D, Lind B. Source: Addiction (Abingdon, England). 2001 April; 96(4): 577-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300961&dopt=Abstract
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Subcutaneous methadone in terminally ill patients: manageable local toxicity. Author(s): Mathew P, Storey P. Source: Journal of Pain and Symptom Management. 1999 July; 18(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439572&dopt=Abstract
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Subcutaneous methadone in terminally-ill patients. Author(s): Makin MK. Source: Journal of Pain and Symptom Management. 2000 April; 19(4): 237-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866549&dopt=Abstract
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Subjective and objective symptoms in relation to plasma methadone concentration in methadone patients. Author(s): Hiltunen AJ, Lafolie P, Martel J, Ottosson EC, Boreus LO, Beck O, Borg S, Hjemdahl P. Source: Psychopharmacology. 1995 March; 118(2): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7617797&dopt=Abstract
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Substitution pharmacotherapies for opioid addiction: from methadone to LAAM and buprenorphine. Author(s): Ling W, Rawson RA, Compton MA. Source: J Psychoactive Drugs. 1994 April-June; 26(2): 119-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7931856&dopt=Abstract
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Successful use of methadone in nociceptive cancer pain unresponsive to morphine. Author(s): Leng G, Finnegan MJ. Source: Palliative Medicine. 1994; 8(2): 153-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7521715&dopt=Abstract
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Successful use of methadone in the treatment of chronic neuropathic pain arising from burn injuries: a case-study. Author(s): Altier N, Dion D, Boulanger A, Choiniere M. Source: Burns : Journal of the International Society for Burn Injuries. 2001 November; 27(7): 771-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600260&dopt=Abstract
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Successful use of oral methadone after failure of intravenous morphine and ketamine. Author(s): Sartain JB, Mitchell SJ. Source: Anaesthesia and Intensive Care. 2002 August; 30(4): 487-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180591&dopt=Abstract
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Sudden death in an adult taking methadone: lessons for general practice. Author(s): Fahey T, Law F, Cottee H, Astley P. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2003 June; 53(491): 471-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939893&dopt=Abstract
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Supervised administration of methadone by pharmacists. Author(s): Scott RT, Burnett SJ, McNutty H. Source: Bmj (Clinical Research Ed.). 1994 May 28; 308(6941): 1438. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8019267&dopt=Abstract
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Supporting problem drug users: improving methadone maintenance in general practice. Author(s): Wilson P, Watson R, Ralston GE. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1995 September; 45(398): 454-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7546865&dopt=Abstract
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Suppressed prolactin response to dynorphin A1-13 in methadone-maintained versus control subjects. Author(s): Bart G, Borg L, Schluger JH, Green M, Ho A, Kreek MJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 August; 306(2): 581-7. Epub 2003 May 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730354&dopt=Abstract
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Suppression of human peripheral blood mononuclear cell function by methadone and morphine. Author(s): Peterson PK, Gekker G, Brummitt C, Pentel P, Bullock M, Simpson M, Hitt J, Sharp B. Source: The Journal of Infectious Diseases. 1989 March; 159(3): 480-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2536791&dopt=Abstract
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Survey assessment of methadone treatment services as reinforcers. Author(s): Chutuape MA, Silverman K, Stitzer ML. Source: The American Journal of Drug and Alcohol Abuse. 1998 February; 24(1): 1-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9513626&dopt=Abstract
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Survival study of opioid addicts in relation to its adherence to methadone maintenance treatment. Author(s): Esteban J, Gimeno C, Barril J, Aragones A, Climent JM, de la Cruz Pellin M. Source: Drug and Alcohol Dependence. 2003 May 21; 70(2): 193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732413&dopt=Abstract
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Suspected determinants of enrollment into detoxification and methadone maintenance treatment among injecting drug users. Author(s): Schutz CG, Rapiti E, Vlahov D, Anthony JC. Source: Drug and Alcohol Dependence. 1994 October; 36(2): 129-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7851280&dopt=Abstract
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Sustained cocaine abstinence in methadone maintenance patients through voucherbased reinforcement therapy. Author(s): Silverman K, Higgins ST, Brooner RK, Montoya ID, Cone EJ, Schuster CR, Preston KL. Source: Archives of General Psychiatry. 1996 May; 53(5): 409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624184&dopt=Abstract
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Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. Author(s): Mercadante S, Casuccio A, Fulfaro F, Groff L, Boffi R, Villari P, Gebbia V, Ripamonti C. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 June 1; 19(11): 2898-904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11387363&dopt=Abstract
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Switching to methadone. Author(s): Enck RE. Source: Am J Hosp Palliat Care. 2001 May-June; 18(3): 149-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406883&dopt=Abstract
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Taste function in methadone-maintained opioid-dependent men. Author(s): Bogucka-Bonikowska A, Baran-Furga H, Chmielewska K, Habrat B, Scinska A, Kukwa A, Koros E, Kostowski W, Polanowska E, Bienkowski P. Source: Drug and Alcohol Dependence. 2002 September 1; 68(1): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167557&dopt=Abstract
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The 2-year test-retest reliability of the Psychopathy Checklist Revised in methadone patients. Author(s): Rutherford M, Cacciola JS, Alterman AI, McKay JR, Cook TG. Source: Assessment. 1999 September; 6(3): 285-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10445965&dopt=Abstract
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The activity of beta-hexosaminidase (uHex) and gamma-glutamyltransferase (uGGT) in urine as non-invasive markers of chronic alcohol abuse: II. Opiate-dependent subjects receiving methadone substitution. Author(s): Taracha E, Habrat B, Baran H, Chmielewska K, Walkowiak J, Szukalski B. Source: World J Biol Psychiatry. 2002 January; 3(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479087&dopt=Abstract
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The analysis of methadone in nail clippings from patients in a methadonemaintenance program. Author(s): Lemos NP, Anderson RA, Robertson JR. Source: Journal of Analytical Toxicology. 2000 October; 24(7): 656-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043676&dopt=Abstract
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The autonomy of mood disorders among cocaine-using methadone patients. Author(s): Rosenblum A, Fallon B, Magura S, Handelsman L, Foote J, Bernstein D. Source: The American Journal of Drug and Alcohol Abuse. 1999 February; 25(1): 67-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10078978&dopt=Abstract
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The changes in spirometric measurements during 6 months' methadone maintenance treatment in opiate dependent patients. Author(s): Targosz D, Kolarzyk E, Pach D. Source: Przegl Lek. 2001; 58(4): 254-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450347&dopt=Abstract
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The converging epidemics of mood-altering-drug use, HIV, HCV, and partner violence: a conundrum for methadone maintenance treatment. Author(s): Gilbert L, El-Bassel N, Rajah V, Foleno A, Fontdevila J, Frye V, Richman BL. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 452-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064497&dopt=Abstract
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The D(2) dopamine receptor A(1) allele and opioid dependence: association with heroin use and response to methadone treatment. Author(s): Lawford BR, Young RM, Noble EP, Sargent J, Rowell J, Shadforth S, Zhang X, Ritchie T. Source: American Journal of Medical Genetics. 2000 October 9; 96(5): 592-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054765&dopt=Abstract
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The early course of change in methadone maintenance. Author(s): Cacciola JS, Alterman AI, Rutherford MJ, McKay JR, McLellan AT. Source: Addiction (Abingdon, England). 1998 January; 93(1): 41-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624710&dopt=Abstract
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The effect of methadone in vitro on natural killer (NK) activity. Author(s): Ochshorn M, Bodner G, Novick DM, Kreek MJ. Source: Nida Res Monogr. 1989; 95: 522-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2641048&dopt=Abstract
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The effect of sertraline on methadone plasma levels in methadone-maintenance patients. Author(s): Hamilton SP, Nunes EV, Janal M, Weber L. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2000 Winter; 9(1): 63-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914294&dopt=Abstract
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The effect of stimulant and sedative use on treatment outcome of patients admitted to methadone maintenance treatment. Author(s): DeMaria PA Jr, Sterling R, Weinstein SP. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2000 Spring; 9(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10934576&dopt=Abstract
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The effectiveness of incentives in enhancing treatment attendance and drug abstinence in methadone-maintained pregnant women. Author(s): Jones HE, Haug N, Silverman K, Stitzer M, Svikis D. Source: Drug and Alcohol Dependence. 2001 February 1; 61(3): 297-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164694&dopt=Abstract
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The effects of methadone treatment on the reactivity of the nonstress test. Author(s): Archie CL, Lee MI, Sokol RJ, Norman G. Source: Obstetrics and Gynecology. 1989 August; 74(2): 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2748062&dopt=Abstract
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The impact of harm-reduction-based methadone treatment on mortality among heroin users. Author(s): Langendam MW, van Brussel GH, Coutinho RA, van Ameijden EJ. Source: American Journal of Public Health. 2001 May; 91(5): 774-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344886&dopt=Abstract
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The impact of hepatitis C virus infection on methadone maintenance treatment. Author(s): Novick DM. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 437-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064495&dopt=Abstract
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The impact of methadone induction on cardiac conduction in opiate users. Author(s): Martell BA, Arnsten JH, Ray B, Gourevitch MN. Source: Annals of Internal Medicine. 2003 July 15; 139(2): 154-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859171&dopt=Abstract
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The impact of methadone treatment on registered convictions and arrests in HIVpositive and HIV-negative men and women with one or more treatment periods. Author(s): Stenbacka M, Leifman A, Romelsjo A. Source: Drug and Alcohol Review. 2003 March; 22(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745356&dopt=Abstract
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The impact on retention of expansion of an Australian public methadone program. Author(s): Bammer G, Battisson L, Ward J, Wilson S. Source: Drug and Alcohol Dependence. 2000 February 1; 58(1-2): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669069&dopt=Abstract
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The influence of coping and depression on abstinence from illicit drug use in methadone-maintained patients. Author(s): Avants SK, Warburton LA, Margolin A. Source: The American Journal of Drug and Alcohol Abuse. 2000 August; 26(3): 399-416. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10976665&dopt=Abstract
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The injection of methadone and benzodiazepines among Sydney injecting drug users 1996-2000: 5-year monitoring of trends from the Illicit Drug Reporting System. Author(s): Darke S, Topp L, Ross J. Source: Drug and Alcohol Review. 2002 March; 21(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189001&dopt=Abstract
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The Key Extended Entry Program (KEEP): a methadone treatment program for opiatedependent inmates. Author(s): Tomasino V, Swanson AJ, Nolan J, Shuman HI. Source: The Mount Sinai Journal of Medicine, New York. 2001 January; 68(1): 14-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135501&dopt=Abstract
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The long-term outcomes of drug use by methadone maintenance patients. Author(s): Bovasso G, Cacciola J. Source: The Journal of Behavioral Health Services & Research. 2003 July-September; 30(3): 290-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875097&dopt=Abstract
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The merits of methadone. Author(s): McCaffery M, Pasero C. Source: The American Journal of Nursing. 2000 July; 100(7): 22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914063&dopt=Abstract
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The methadone-maintained pregnancy. Author(s): Kandall SR, Doberczak TM, Jantunen M, Stein J. Source: Clin Perinatol. 1999 March; 26(1): 173-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10214548&dopt=Abstract
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The pharmacokinetics of methadone following co-administration with a lamivudine/zidovudine combination tablet in opiate-dependent subjects. Author(s): Rainey PM, Friedland GH, Snidow JW, McCance-Katz EF, Mitchell SM, Andrews L, Lane B, Jatlow P. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2002 Winter; 11(1): 66-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876585&dopt=Abstract
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The pharmacokinetics of methadone in HIV-positive patients receiving the nonnucleoside reverse transcriptase inhibitor efavirenz. Author(s): Clarke SM, Mulcahy FM, Tjia J, Reynolds HE, Gibbons SE, Barry MG, Back DJ. Source: British Journal of Clinical Pharmacology. 2001 March; 51(3): 213-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298066&dopt=Abstract
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The prediction of violent and nonviolent criminal behavior in a methadone maintenance population. Author(s): Bovasso GB, Alterman AI, Cacciola JS, Rutherford MJ. Source: Journal of Personality Disorders. 2002 August; 16(4): 360-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224128&dopt=Abstract
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The protease inhibitor lopinavir-ritonavir may produce opiate withdrawal in methadone-maintained patients. Author(s): McCance-Katz EF, Rainey PM, Friedland G, Jatlow P. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 15; 37(4): 476-82. Epub 2003 Aug 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905130&dopt=Abstract
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The rediscovery of methadone for cancer pain management. Author(s): Clark KJ, Turner K. Source: The Medical Journal of Australia. 2001 May 21; 174(10): 547-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419789&dopt=Abstract
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The rediscovery of methadone for cancer pain management. Author(s): Ayonrinde OT, Bridge DT. Source: The Medical Journal of Australia. 2000 November 20; 173(10): 536-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194738&dopt=Abstract
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The relationship between mood state and plasma methadone concentration in maintenance patients. Author(s): Dyer KR, White JM, Foster DJ, Bochner F, Menelaou A, Somogyi AA. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 78-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199952&dopt=Abstract
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The relationship between suicide and heroin overdose among methadone maintenance patients in Sydney, Australia. Author(s): Darke S, Ross J. Source: Addiction (Abingdon, England). 2001 October; 96(10): 1443-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571063&dopt=Abstract
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The relationship of conduct disorder to attempted suicide and drug use history among methadone maintenance patients. Author(s): Darke S, Ross J, Lynskey M. Source: Drug and Alcohol Review. 2003 March; 22(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745355&dopt=Abstract
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The relationship of methadone dose and other variables to outcomes of methadone maintenance. Author(s): Maddux JF, Prihoda TJ, Vogtsberger KN. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 1997 Summer; 6(3): 246-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9256991&dopt=Abstract
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The relationship of psychiatric comorbidity to treatment outcomes in methadone maintained patients. Author(s): Cacciola JS, Alterman AI, Rutherford MJ, McKay JR, Mulvaney FD. Source: Drug and Alcohol Dependence. 2001 February 1; 61(3): 271-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164691&dopt=Abstract
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The role of methadone in drug-related deaths in the west of Scotland. Author(s): Seymour A, Black M, Jay J, Cooper G, Weir C, Oliver J. Source: Addiction (Abingdon, England). 2003 July; 98(7): 995-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814505&dopt=Abstract
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The Supervised Methadone and Resettlement Team nurse: an effective approach with opiate-dependent, homeless people. Author(s): Mistral W, Hollingworth M. Source: International Nursing Review. 2001 June; 48(2): 122-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407458&dopt=Abstract
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The use of levo-alpha-acetylmethadol (LAAM) in methadone patients who have not achieved heroin abstinence. Author(s): Borg L, Ho A, Wells A, Joseph H, Appel P, Moody D, Kreek MJ. Source: J Addict Dis. 2002; 21(3): 13-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094997&dopt=Abstract
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The use of methadone for cancer pain. Author(s): Ripamonti C, Bianchi M. Source: Hematology/Oncology Clinics of North America. 2002 June; 16(3): 543-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170567&dopt=Abstract
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The validity of drug users' self-reports in a non-treatment setting: prevalence and predictors of incorrect reporting methadone treatment modalities. Author(s): Langendam MW, van Haastrecht HJ, van Ameijden EJ. Source: International Journal of Epidemiology. 1999 June; 28(3): 514-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10405858&dopt=Abstract
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Therapeutic drug monitoring for methadone: scanning the horizon. Author(s): Wolff K, Strang J. Source: European Addiction Research. 1999 March; 5(1): 36-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10085499&dopt=Abstract
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Therapeutic drug monitoring in methadone maintenance: choosing a matrix. Author(s): Moolchan ET, Umbricht A, Epstein D. Source: J Addict Dis. 2001; 20(2): 55-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318398&dopt=Abstract
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Thoracotomy without opioids in a heroin addict maintained with oral methadone. Author(s): Voyagis GS, Dimitriou V, Semeophoridou M, Tragou A. Source: European Journal of Anaesthesiology. 1998 November; 15(6): 806-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9884877&dopt=Abstract
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Three oral formulations of methadone. A clinical and pharmacodynamic comparison. Author(s): Gourevitch MN, Hartel D, Tenore P, Freeman K, Marion I, Hecht J, Lowinson J. Source: Journal of Substance Abuse Treatment. 1999 October; 17(3): 237-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10531630&dopt=Abstract
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Tobacco use and quit attempts among methadone maintenance clients. Author(s): Richter KP, Gibson CA, Ahluwalia JS, Schmelzle KH. Source: American Journal of Public Health. 2001 February; 91(2): 296-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11211643&dopt=Abstract
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Torsade de pointes associated with very-high-dose methadone. Author(s): Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Source: Annals of Internal Medicine. 2002 September 17; 137(6): 501-4. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230351&dopt=Abstract
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Torsade de pointes due to methadone. Author(s): Sala M, Anguera I, Cervantes M. Source: Annals of Internal Medicine. 2003 August 19; 139(4): W64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966001&dopt=Abstract
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Torsade de pointes due to methadone. Author(s): Mokwe EO, Ositadinma O. Source: Annals of Internal Medicine. 2003 August 19; 139(4): W64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966000&dopt=Abstract
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Torsades de pointes due to methadone. Author(s): De Bels D, Staroukine M, Devriendt J. Source: Annals of Internal Medicine. 2003 July 15; 139(2): E156. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859181&dopt=Abstract
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Toxicology and pathology of deaths related to methadone: retrospective review. Author(s): Karch SB, Stephens BG. Source: The Western Journal of Medicine. 2000 January; 172(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695434&dopt=Abstract
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Treating cocaine-using methadone patients: predictors of outcomes in a psychosocial clinical trial. Author(s): Magura S, Rosenblum A, Fong C, Villano C, Richman B. Source: Substance Use & Misuse. 2002; 37(14): 1927-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511059&dopt=Abstract
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Treating hepatitis C in methadone maintenance patients: an interim analysis. Author(s): Sylvestre DL. Source: Drug and Alcohol Dependence. 2002 July 1; 67(2): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095661&dopt=Abstract
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Treating heroin addiction: comparison of methadone therapy, hospital therapy without methadone, and therapeutic community. Author(s): Vidjak N. Source: Croatian Medical Journal. 2003 February; 44(1): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590430&dopt=Abstract
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Treatment of neonatal abstinence syndrome with breast milk containing methadone. Author(s): Ballard JL. Source: The Journal of Perinatal & Neonatal Nursing. 2002 March; 15(4): 76-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911622&dopt=Abstract
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Treatment of pain in chronic bowel subobstruction with self-administration of methadone. Author(s): Mercadante S, Sapio M, Serretta R. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 1997 July; 5(4): 327-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9257431&dopt=Abstract
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Treatment of pain in methadone-maintained patients. Author(s): Scimeca MM, Savage SR, Portenoy R, Lowinson J. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 412-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064492&dopt=Abstract
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Trends in drug overdose deaths in England and Wales 1993-98: methadone does not kill more people than heroin. Author(s): Hickman M, Madden P, Henry J, Baker A, Wallace C, Wakefield J, Stimson G, Elliott P. Source: Addiction (Abingdon, England). 2003 April; 98(4): 419-25. Erratum In: Addiction. 2003 September; 98(9): 1325-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653812&dopt=Abstract
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Trends in HIV risk behaviour and methadone dosage among HIV-negative drug users: an ecological study. Author(s): Langendam MW, van Brussel GH, Coutinho RA, van Ameijden EJ. Source: Aids (London, England). 2000 August 18; 14(12): 1870-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10985334&dopt=Abstract
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Tuberculosis chemoprophylaxis using a liquid isoniazid-methadone admixture for drug users in methadone maintenance. Author(s): O'Connor PG, Shi JM, Henry S, Durante AJ, Friedman L, Selwyn PA. Source: Addiction (Abingdon, England). 1999 July; 94(7): 1071-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10707445&dopt=Abstract
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Ultrafiltration using the Amicon MPS-1 for assessing methadone plasma protein binding. Author(s): Wilkins JN, Ashofteh A, Setoda D, Wheatley WS, Huigen H, Ling W. Source: Therapeutic Drug Monitoring. 1997 February; 19(1): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9029753&dopt=Abstract
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Ultra-low dose oral naltrexone decreases side effects and potentiates the effect of methadone. Author(s): Cruciani RA, Lussier D, Miller-Saultz D, Arbuck DM. Source: Journal of Pain and Symptom Management. 2003 June; 25(6): 491-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782427&dopt=Abstract
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Ultrarapid high-dose methadone detoxification. Author(s): Prieto IJ, Poyo-Guerrero R, Fernandez R, Ochoa E. Source: Psychopharmacology. 2003 February; 165(4): 430. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491030&dopt=Abstract
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Undefined duration of opiate withdrawal induced by efavirenz in drug users with HIV infection and undergoing chronic methadone treatment. Author(s): Boffito M, Rossati A, Reynolds HE, Hoggard PG, Back DJ, Di Perri G. Source: Aids Research and Human Retroviruses. 2002 March 20; 18(5): 341-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897035&dopt=Abstract
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Understanding condom use among heroin addicts in methadone maintenance using the information-motivation-behavioral skills model. Author(s): Bryan AD, Fisher JD, Fisher WA, Murray DM. Source: Substance Use & Misuse. 2000 March; 35(4): 451-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741537&dopt=Abstract
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Unmet service needs in methadone maintenance. Author(s): Joe GW, Simpson DD, Hubbard RL. Source: Int J Addict. 1991 January; 26(1): 1-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2066169&dopt=Abstract
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Unusual cause of methadone poisoning. Author(s): Gayle MO, Ryan CA, Nazarali S. Source: Acta Paediatr Scand. 1991 April; 80(4): 486-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2058403&dopt=Abstract
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Urban community reaction to health facilities in residential areas: lessons from the placement of methadone facilities in New York City. Author(s): Genevie L, Struening EL, Kallos JE, Geiler I, Muhlin GL, Kaplan S. Source: Int J Addict. 1988 June; 23(6): 603-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3170049&dopt=Abstract
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Urinary amphetamines, benzodiazepines and methadone: cost-effective detection procedures. Author(s): Moore FM, Jarvie DR, Simpson D. Source: Med Lab Sci. 1992 March; 49(1): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1453905&dopt=Abstract
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Urine screening practices in methadone maintenance clinics. A survey of how the results are used. Author(s): Calsyn DA, Saxon AJ, Barndt DC. Source: The Journal of Nervous and Mental Disease. 1991 April; 179(4): 222-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2007893&dopt=Abstract
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Use of a constraint satisfaction network model for the evaluation of the methadone treatments of drug addicts. Author(s): Massini G, Shabtay L. Source: Substance Use & Misuse. 1998 February; 33(3): 625-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9533733&dopt=Abstract
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Use of antiretroviral therapies by HIV-infected persons receiving methadone maintenance. Author(s): Stein MD, Urdaneta ME, Clarke J, Maksad J, Sobota M, Hanna L, Markson LE. Source: J Addict Dis. 2000; 19(1): 85-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772605&dopt=Abstract
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Use of general practice by intravenous heroin users on a methadone programme. Author(s): Leaver EJ, Elford J, Morris JK, Cohen J. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1992 November; 42(364): 465-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1472393&dopt=Abstract
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Use of intrathecal hyperbaric methadone in postoperative analgesia of thoracic surgery. Author(s): Fernandez-Liesa JI, Panadero A. Source: Regional Anesthesia and Pain Medicine. 2000 May-June; 25(3): 325. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834796&dopt=Abstract
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Use of large particles support for fast analysis of methadone and its primary metabolite in human plasma by liquid chromatography-mass spectrometry. Author(s): Souverain S, Rudaz S, Ortelli D, Varesio E, Veuthey JL. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 January 25; 784(1): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504189&dopt=Abstract
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Use of methadone in a highly tolerant patient receiving parenteral hydromorphone. Author(s): Thomas Z, Bruera E. Source: Journal of Pain and Symptom Management. 1995 May; 10(4): 315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7541438&dopt=Abstract
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Use of methadone in the morphine-tolerant burned paediatric patient. Author(s): Williams PI, Sarginson RE, Ratcliffe JM. Source: British Journal of Anaesthesia. 1998 January; 80(1): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9505787&dopt=Abstract
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Use of methadone take-home contingencies with persistent opiate and cocaine abusers. Author(s): Chutuape MA, Silverman K, Stitzer ML. Source: Journal of Substance Abuse Treatment. 1999 January; 16(1): 23-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888118&dopt=Abstract
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Use of methadone. Author(s): Anderson IB, Kearney TE. Source: The Western Journal of Medicine. 2000 January; 172(1): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10695444&dopt=Abstract
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Use of solid-phase microextraction (SPME) for the determination of methadone and EDDP in human hair by GC-MS. Author(s): Lucas AC, Bermejo AM, Tabernero MJ, Fernandez P, Strano-Rossi S. Source: Forensic Science International. 2000 January 10; 107(1-3): 225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10689574&dopt=Abstract
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Use of solid-phase microextraction (SPME) for the determination of methadone and its main metabolite, EDDP, in plasma by gas chromatography-mass spectrometry. Author(s): Bermejo AM, Seara R, dos Santos Lucas AC, Tabernero MJ, Fernandez P, Marsili R. Source: Journal of Analytical Toxicology. 2000 January-February; 24(1): 66-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10654572&dopt=Abstract
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Use of the Nottingham Health Profile for measuring health status of patients in methadone maintenance treatment. Author(s): Torrens M, San L, Martinez A, Castillo C, Domingo-Salvany A, Alonso J. Source: Addiction (Abingdon, England). 1997 June; 92(6): 707-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9246798&dopt=Abstract
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Use of 'very low-dose phenobarbital' to investigate compliance in patients on reducing doses of methadone (detoxification). Author(s): Wolff K, Hay AA, Raistrick D, Feely M. Source: Journal of Substance Abuse Treatment. 1993 September-October; 10(5): 453-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8246320&dopt=Abstract
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Users of free treatment slots at a community-based methadone maintenance clinic. Author(s): Wells EA, Fleming C, Calsyn DA, Jackson TR, Saxon AJ. Source: Journal of Substance Abuse Treatment. 1995 January-February; 12(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7752292&dopt=Abstract
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Using latent-variable models to analyze smoking cessation clinical trial data: an example among the methadone maintained. Author(s): Frosch DL, Stein JA, Shoptaw S. Source: Experimental and Clinical Psychopharmacology. 2002 August; 10(3): 258-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233986&dopt=Abstract
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Using methadone effectively: achieving goals by application of laboratory, clinical, and evaluation research and by development of innovative programs. Author(s): Kreek MJ. Source: Nida Res Monogr. 1991; 106: 245-66. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1922290&dopt=Abstract
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Utilization of on-site primary care services by HIV-seropositive and seronegative drug users in a methadone maintenance program. Author(s): Selwyn PA, Budner NS, Wasserman WC, Arno PS. Source: Public Health Reports (Washington, D.C. : 1974). 1993 July-August; 108(4): 492500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8393579&dopt=Abstract
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Utilization of plasma and urine methadone concentration measurements to limit narcotics use in methadone maintenance patients: II. Generation of plasma concentration response curves. Author(s): Kell MJ. Source: J Addict Dis. 1995; 14(1): 85-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7632750&dopt=Abstract
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Utilization of plasma and urine methadone concentrations to optimize treatment in maintenance clinics: I. Measurement techniques for a clinical setting. Author(s): Kell MJ. Source: J Addict Dis. 1994; 13(1): 5-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8018740&dopt=Abstract
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Validation of MMPI profile subtypes among opioid addicts who are beginning methadone maintenance treatment. Author(s): Calsyn DA, Roszell DK, Chaney EF. Source: Journal of Clinical Psychology. 1989 November; 45(6): 991-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2613912&dopt=Abstract
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Validity of the psychopathy checklist-revised in male methadone patients. Author(s): Rutherford MJ, Alterman AI, Cacciola JS, McKay JR. Source: Drug and Alcohol Dependence. 1997 March 14; 44(2-3): 143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088786&dopt=Abstract
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Validity of three measures of antisociality in predicting HIV risk behaviors in methadone-maintenance patients. Author(s): Tourian K, Alterman A, Metzger D, Rutherford M, Cacciola JS, McKay JR. Source: Drug and Alcohol Dependence. 1997 August 25; 47(2): 99-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9298331&dopt=Abstract
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Valium use and abuse by methadone maintenance clients. Author(s): Hartog J, Tusel DJ. Source: Int J Addict. 1987 November; 22(11): 1147-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3429073&dopt=Abstract
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Valproic acid, unlike other anticonvulsants, has no effect on methadone metabolism: two cases. Author(s): Saxon AJ, Whittaker S, Hawker CS. Source: The Journal of Clinical Psychiatry. 1989 June; 50(6): 228-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2498296&dopt=Abstract
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Variations in methadone treatment practices. Author(s): Magura S. Source: Jama : the Journal of the American Medical Association. 1992 August 19; 268(7): 870-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1640604&dopt=Abstract
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Variations in methadone treatment practices. Results from a national study. Author(s): D'Aunno T, Vaughn TE. Source: Jama : the Journal of the American Medical Association. 1992 January 8; 267(2): 253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1727522&dopt=Abstract
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Ventilatory effects of morphine, pethidine and methadone in children. Author(s): Hamunen K. Source: British Journal of Anaesthesia. 1993 April; 70(4): 414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8499200&dopt=Abstract
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Voltammetric assay of methadone in urine. Author(s): Barreira Rodriguez JR, Costa Garcia A, Tunon Blanco P. Source: The Analyst. 1989 August; 114(8): 939-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2802169&dopt=Abstract
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Voucher-based reinforcement of attendance by unemployed methadone patients in a job skills training program. Author(s): Silverman K, Chutuape MA, Bigelow GE, Stitzer ML. Source: Drug and Alcohol Dependence. 1996 July; 41(3): 197-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8842632&dopt=Abstract
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Voucher-based reinforcement of cocaine abstinence in treatment-resistant methadone patients: effects of reinforcement magnitude. Author(s): Silverman K, Chutuape MA, Bigelow GE, Stitzer ML. Source: Psychopharmacology. 1999 September; 146(2): 128-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525747&dopt=Abstract
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Voucher-based reinforcement of opiate abstinence during methadone detoxification. Author(s): Robles E, Stitzer ML, Strain EC, Bigelow GE, Silverman K. Source: Drug and Alcohol Dependence. 2002 January 1; 65(2): 179-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772479&dopt=Abstract
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Voucher-based reinforcement of opiate plus cocaine abstinence in treatment-resistant methadone patients: effects of reinforcer magnitude. Author(s): Dallery J, Silverman K, Chutuape MA, Bigelow GE, Stitzer ML. Source: Experimental and Clinical Psychopharmacology. 2001 August; 9(3): 317-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11534542&dopt=Abstract
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When “enough” is not enough: new perspectives on optimal methadone maintenance dose. Author(s): Leavitt SB, Shinderman M, Maxwell S, Eap CB, Paris P. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 404-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064491&dopt=Abstract
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When is less treatment better? The role of social anxiety in matching methadone patients to psychosocial treatments. Author(s): Avants SK, Margolin A, Kosten TR, Rounsaville BJ, Schottenfeld RS. Source: Journal of Consulting and Clinical Psychology. 1998 December; 66(6): 924-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9874905&dopt=Abstract
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Who should receive methadone maintenance? Author(s): Bell J, Digiusto E, Byth K. Source: British Journal of Addiction. 1992 May; 87(5): 689-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1591519&dopt=Abstract
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Withdrawal from heroin and methadone. Author(s): Travers R. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1991 October; 159: 582-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1751876&dopt=Abstract
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Withdrawal from methadone maintenance treatment. Reasons for not trying to quit methadone. Author(s): Hiltunen AJ, Eklund C. Source: European Addiction Research. 2002 January; 8(1): 38-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818692&dopt=Abstract
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Withdrawal from methadone maintenance treatment: prognosis and participant perspectives. Author(s): Lenne M, Lintzeris N, Breen C, Harris S, Hawken L, Mattick R, Ritter A. Source: Aust N Z J Public Health. 2001 April; 25(2): 121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357906&dopt=Abstract
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Withdrawal from methadone maintenance. Impact of a tapering network support program. Author(s): Sorensen JL, Trier M, Brummett S, Gold ML, Dumontet R. Source: Journal of Substance Abuse Treatment. 1992; 9(1): 21-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1593661&dopt=Abstract
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CHAPTER 2. NUTRITION AND METHADONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and methadone.
Finding Nutrition Studies on Methadone The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “methadone” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “methadone” (or a synonym): •
A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users. Author(s): Department of Psychiatry, State University of New York Upstate Medical University, 750 East Adams St., Syracuse 13210, USA.
[email protected] Source: Batki, Steven L Gruber, Valerie A Bradley, Julia Moon Bradley, Mark Delucchi, Kevin Drug-Alcohol-Depend. 2002 May 1; 66(3): 283-93 0376-8716
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A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients. Author(s): Veteran's Affairs Medical Center, University & Woodland Aves., Philadelphia, PA 19104, USA.
[email protected] Source: Cornish, J W Herman, B H Ehrman, R N Robbins, S J Childress, A R Bead, V Esmonde, C A Martz, K Poole, S Caruso, F S O'Brien, C P Drug-Alcohol-Depend. 2002 July 1; 67(2): 177-83 0376-8716
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Acute physical dependence in humans: repeated naloxone-precipitated withdrawal after a single dose of methadone. Author(s): Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland. Source: Wright, C Bigelow, G E Stitzer, M L Liebson, I A Drug-Alcohol-Depend. 1991 March; 27(2): 139-48 0376-8716
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An increase in overdose mortality during the first 2 weeks after entering or reentering methadone treatment in Amsterdam. Author(s): Department of Epidemiology, Documentationa nd Health Promotion, Municipal Health Service, Amsterdam, The Netherlands.
[email protected] Source: Buster, M C van Brussel, G H van den Brink, W Addiction. 2002 August; 97(8): 993-1001 0965-2140
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Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Author(s): Department of General Psychiatry, University Hospital of Vienna, Austria. Source: Fischer, G Gombas, W Eder, H Jagsch, R Peternell, A Stuhlinger, G Pezawas, L Aschauer, H N Kasper, S Addiction. 1999 September; 94(9): 1337-47 0965-2140
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Canadian illicit opiate users' views on methadone and other opiate prescription treatment: an exploratory qualitative study. Author(s): Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
[email protected] Source: Fischer, B Chin, A T Kuo, I Kirst, M Vlahov, D Subst-Use-Misuse. 2002 March; 37(4): 495-522 1082-6084
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Combined naloxone/methadone preparations for opiate substitution therapy. Author(s): Department of Psychiatry, University of Vienna, Austria. Source: Loimer, N Presslich, O Grunberger, J Linzmayer, L J-Subst-Abuse-Treat. 1991; 8(3): 157-60 0740-5472
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Combined use of trazodone-naltrexone versus clonidine-naltrexone in rapid withdrawal from methadone treatment. A comparative inpatient study. Author(s): Clinical Psychiatry and Substance Dependence Unit, Institute of Psychiatry and Psychology, Faculty of Medicine 'Agostino Gemelli', Catholic University of the Sacred Heart, 00168, Rome, Italy.
[email protected]
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Source: Pozzi, G Conte, G De Risio, S Drug-Alcohol-Depend. 2000 June 1; 59(3): 287-94 0376-8716 •
Comparison of buprenorphine and methadone in the treatment of opioid dependence. Swiss multicentre study. Author(s): Psychosocial Centre of Fribourg, Fribourg, Switzerland. Source: Uehlinger, C Deglon, J Livoti, S Petitjean, S Waldvogel, D Ladewig, D EurAddict-Res. 1998; 4 Suppl 113-8 1022-6877
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Comparison of buprenorphine and methadone maintenance in opiate addicts. Author(s): Department of General Psychiatry, University Hospital of Psychiatry, Wahringer Gurtel, Vienna, Austria.
[email protected] Source: Eder, H Fischer, G Gombas, W Jagsch, R Stuhlinger, G Kasper, S Eur-AddictRes. 1998; 4 Suppl 13-7 1022-6877
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Comparison of methadone and slow-release morphine maintenance in pregnant addicts. Author(s): Department of General Psychiatry, University Hospital of Vienna, Austria.
[email protected] Source: Fischer, G Jagsch, R Eder, H Gombas, W Etzersdorfer, P Schmidl Mohl, K Schatten, C Weninger, M Aschauer, H N Addiction. 1999 February; 94(2): 231-9 09652140
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Conversion from intrathecal morphine to oral methadone. Author(s): Department of Anesthesiology, Division of Pain Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. Source: Gebhardt, Rodolfo Kinney, Michelle A O Reg-Anesth-Pain-Med. 2002 May-June; 27(3): 319-21 1098-7339
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Effects of “binge” use of intravenous cocaine in methadone-maintained individuals. Author(s): Division on Substance Abuse, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
[email protected] Source: Foltin, R W Fischman, M W Addiction. 1998 June; 93(6): 825-36 0965-2140
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Effects of nicotine on methadone self-administration in humans. Author(s): Department of Psychiatry and Behavioral Sciences, Houston, TX 77030, USA.
[email protected] Source: Spiga, R Schmitz, J Day, J Drug-Alcohol-Depend. 1998 April 1; 50(2): 157-65 0376-8716
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Effects of prolonged exposure to morphine and methadone on in vivo parameters of immune function in rats. Author(s): Laboratory for Medicines and Medical Devices, National Insitute for Public Health and the Environment, Bilthoven, Netherlands.
[email protected] Source: De Waal, E J Van Der Laan, J W Van Loveren, H Toxicology. 1998 August 21; 129(2-3): 201-10 0300-483X
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Emergency therapeutical approach simulating ultrarapid opioid detoxification in methadone withdrawal precipitated by erroneous administration of naltrexone. Author(s): Poison Control Centre, Policlinico Agostino Gemelli, School of Medicine, Catholic University of Rome, Italy. Source: De Giacomo, M Gaspari, R Stefanelli, A Barelli, A Mannelli, P Eur-J-Emerg-Med. 1999 June; 6(2): 153-5 0969-9546
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Fluoxetine for cocaine abuse in methadone patients: preliminary findings. Author(s): Dept. of Psychiatry, UCSF.
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Source: Batki, S L Manfredi, L B Sorensen, J L Jacob, P Dumontet, R Jones, R T NIDARes-Monogr. 1991; 105516-7 1046-9516 •
In contrast to cocaine, prenatal exposure to methadone does not produce detectable alterations in the developing mouse brain. Author(s): Cell Biology Unit, Christian de Duve Institute of Cellular Pathology, Louvain University Medical School, 75, Avenue Hippocrate, B-1200, Brussels, Belgium.
[email protected] Source: Nassogne, M C Gressens, P Evrard, P Courtoy, P J Brain-Res-Dev-Brain-Res. 1998 September 10; 110(1): 61-7 0165-3806
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Methadone and heroin prescription: babies and bath water. Author(s): Alcohol and Drug Service, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
[email protected] Source: Wodak, A Subst-Use-Misuse. 2002 March; 37(4): 523-31 1082-6084
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Methadone in treatment of tenesmus not responding to morphine escalation. Author(s): SAMOT, via Liberta 191, 90145 Palermo, Italy.
[email protected] Source: Mercadante, S Fulfaro, F Dabbene, M Support-Care-Cancer. 2001 March; 9(2): 129-30 0941-4355
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Methadone induces CCR5 and promotes AIDS virus infection. Author(s): Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, USA. Source: Suzuki, Shunji Carlos, Maria P Chuang, Linda F Torres, Jose V Doi, Roy H Chuang, Ronald Y FEBS-Lett. 2002 May 22; 519(1-3): 173-7 0014-5793
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Methadone titration in opioid-resistant cancer pain. Author(s): Mount Vernon Hospital, Middlesex, UK. Source: Scholes, C F Gonty, N Trotman, I F Eur-J-Cancer-Care-(Engl). 1999 March; 8(1): 26-9 0961-5423
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Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. Author(s): Pain Relief and Palliative Care, Societa a Maluto Oncologico Terminale, University of Palermo, Italy.
[email protected] Source: Mercadante, S Casuccio, A Agnello, A Serretta, R Calderone, L Barresi, L J-ClinOncol. 1998 November; 16(11): 3656-61 0732-183X
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Neuronal inhibitory effects of methadone are predominantly opioid receptor mediated in the rat spinal cord in vivo. Author(s): Department of Pharmacology, University College, Gower Street, London, WC1E 6BT, UK.
[email protected] Source: Carpenter, K J Chapman, V Dickenson, A H Eur-J-Pain. 2000; 4(1): 19-26 10903801
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One-year mortality rates following methadone treatment discharge. Author(s): Department of Psychiatry, University of Pennsylvania, Philadelphia, USA.
[email protected] Source: Zanis, D A Woody, G E Drug-Alcohol-Depend. 1998 November 1; 52(3): 257-60 0376-8716
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Oral and intravenous methadone use: some clinical and pharmacokinetic aspects. Author(s): Unite Specialisee en Toxicomanie du Centre Psychosocial, Fribourg, Switzerland. Source: Felder, C Uehlinger, C Baumann, P Powell, K Eap, C B Drug-Alcohol-Depend. 1999 June 1; 55(1-2): 137-43 0376-8716
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Orally delivered methadone as a reinforcer: Effects of the opioid antagonist naloxone. Author(s): Department of Psychiatry and Behavioral Sciences, University of TexasHouston Health Science Center, 77030-3497, USA. Source: Wang, N S Stewart, R B Meisch, R A Drug-Alcohol-Depend. 1999 June 1; 55(1-2): 79-84 0376-8716
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Outpatient comparison of buprenorphine and methadone maintenance. I. Effects on opiate use and self-reported adverse effects and withdrawal symptomatology. Author(s): Addiction Research Center, National Institute on Drug Abuse Baltimore, Maryland 21224. Source: Johnson, R E Fudala, P J Jaffe, J H NIDA-Res-Monogr. 1991; 105585-6 1046-9516
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Outpatient comparison of buprenorphine and methadone maintenance. II. Effects on cocaine usage, retention time in study and missed clinic visits. Author(s): Addiction Research Center, National Institute on Drug Abuse Baltimore, Maryland 20857. Source: Fudala, P J Johnson, R E Jaffe, J H NIDA-Res-Monogr. 1991; 105587-8 1046-9516
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Outpatient maintenance/detoxification comparison of methadone and buprenorphine. Author(s): NIDA, Addiction Research Center, Baltimore, MD. Source: Johnson, R E Fudala, P J Collins, C C Jaffe, J H NIDA-Res-Monogr. 1989; 95384 1046-9516
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Rapid cortical hemoglobin deoxygenation after heroin and methadone injection in humans: a preliminary report. Author(s): Department of Psychiatry, University of Zurich, Switzerland.
[email protected] Source: Stohler, R Dursteler, K M Stormer, R Seifritz, E Hug, I Sattler Mayr, J Muller Spahn, F Ladewig, D Hock, C Drug-Alcohol-Depend. 1999 November 1; 57(1): 23-8 03768716
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Rapid switching from morphine to methadone in cancer patients with poor response to morphine. Author(s): Anesthesia and Intensive Care Unit, La Maddalena Clinic for Cancer, Palermo, Italy.
[email protected] Source: Mercadante, S Casuccio, A Calderone, L J-Clin-Oncol. 1999 October; 17(10): 3307-12 0732-183X
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Retention in treatment of heroin users in Italy: the role of treatment type and of methadone maintenance dosage. Author(s): Department of Epidemiology, Lazio Regional Health Authority, Rome, Italy. Source: D'Ippoliti, D Davoli, M Perucci, C A Pasqualini, F Bargagli, A M Drug-AlcoholDepend. 1998 October 1; 52(2): 167-71 0376-8716
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Retention rate and illicit opioid use during methadone maintenance interventions: a meta-analysis. Author(s): Pharmacology Unit (Institut Municipal d'Investigacio Medica-IMIM), Carrer Doctor Aiguador 80, E-08003, Barcelona, Spain.
[email protected] Source: Farre, Magi Mas, Anna Torrens, Marta Moreno, Victor Cami, Jordi DrugAlcohol-Depend. 2002 February 1; 65(3): 283-90 0376-8716
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Slow metabolism and long half life of methadone in a patient with lung cancer and cirrhosis. Author(s): Pharmacie, Hopital Paul-Guiraud, 54, avenue de la Republique, 94806 Villejuif Cedex.
[email protected]
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Source: Beauverie, P Furlan, V Edel, Y A Ann-Med-Interne-(Paris). 2001 November; 152 Suppl 7: 50-2 0003-410X •
Smoking cessation in methadone maintenance. Author(s): Friends Research Institute, Los Angeles, CA, UCLA, Department of Psychiatry, Los Angeles, CA 90025, USA.
[email protected] Source: Shoptaw, S Rotheram Fuller, E Yang, X Frosch, D Nahom, D Jarvik, M E Rawson, R A Ling, W Addiction. 2002 October; 97(10): 1317-28; discussion 1325 09652140
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Substitution with buprenorphine in methadone- and morphine sulfate-dependent patients. Preliminary results. Author(s): Clinique Liberte, Paris, France. Source: Bouchez, J Beauverie, P Touzeau, D Eur-Addict-Res. 1998; 4 Suppl 18-12 10226877
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Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? Author(s): Pain Therapy and Palliative Care Division, National Cancer Institute, Milan, Italy.
[email protected] Source: Ripamonti, C Groff, L Brunelli, C Polastri, D Stavrakis, A De Conno, F J-ClinOncol. 1998 October; 16(10): 3216-21 0732-183X
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Taste function in methadone-maintained opioid-dependent men. Author(s): Department of Pharmacology, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, PL-02957 Warsaw, Poland. Source: Bogucka Bonikowska, A Baran Furga, H Chmielewska, K Habrat, B Scinska, A Kukwa, A Koros, E Kostowski, W Polanowska, E Bienkowski, P Drug-Alcohol-Depend. 2002 September 1; 68(1): 113-7 0376-8716
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The effects of buprenorphine in methadone-dependent volunteers. Author(s): Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Francis Scott Key Medical Center, Baltimore, MD 21224. Source: Strain, E C Bigelow, G E Preston, K L Liebson, I NIDA-Res-Monogr. 1991; 105584 1046-9516
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The merits of methadone. Source: McCaffery, M Pasero, C Am-J-Nurs. 2000 July; 100(7): 22-3 0002-936X
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Time course of naloxone-precipitated withdrawal after acute methadone exposure in humans. Author(s): Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore. Source: Stitzer, M L Wright, C Bigelow, G E June, H L Felch, L J Drug-Alcohol-Depend. 1991 December; 29(1): 39-46 0376-8716
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Treatment of neonatal abstinence syndrome with breast milk containing methadone. Author(s): Department of Pediatrics, Children's Hospital Medical Center, The University Hospital, Inc., Cincinnati, Ohio, USA. Source: Ballard, Jeanne L J-Perinat-Neonatal-Nurs. 2002 March; 15(4): 76-85 0893-2190
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Tuberculosis chemoprophylaxis using a liquid isoniazid-methadone admixture for drug users in methadone maintenance. Author(s): Department of Medicine, Yale University School of Medicine, New Haven, CT 06520-8025, USA. Source: O'Connor, P G Shi, J M Henry, S Durante, A J Friedman, L Selwyn, P A Addiction. 1999 July; 94(7): 1071-5 0965-2140
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND METHADONE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to methadone. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to methadone and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “methadone” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to methadone: •
A comparative study of hypnotherapy and psychotherapy in the treatment of methadone addicts. Author(s): Manganiello AJ. Source: Am J Clin Hypn. 1984 April; 26(4): 273-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6486078&dopt=Abstract
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Acupuncture in methadone withdrawal. Author(s): Man PL, Chuang MY. Source: Int J Addict. 1980 August; 15(6): 921-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7007260&dopt=Abstract
•
Addiction Severity Index scores of four racial/ethnic and gender groups of methadone maintenance patients. Author(s): Brown LS Jr, Alterman AI, Rutherford MJ, Cacciola JS, Zaballero AR.
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Source: Journal of Substance Abuse. 1993; 5(3): 269-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8312732&dopt=Abstract •
Admissions to methadone maintenance: comparisons between programs and implications for treatment. Author(s): Corty E, Ball JC. Source: Journal of Substance Abuse Treatment. 1987; 4(3-4): 181-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3437483&dopt=Abstract
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An apparent epidemic: methadone poisoning in children. Author(s): Aronow R, Brenner SL, Woolley PV Jr. Source: Clin Toxicol. 1973; 6(2): 175-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4146005&dopt=Abstract
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An innovative approach to methadone detoxification. Author(s): Milkman H, Metcalf D, Reed P. Source: Int J Addict. 1980 November; 15(8): 1199-211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7216560&dopt=Abstract
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Attenuation of precipitated abstinence in methadone-dependent rats by delta 9-THC. Author(s): Hine B, Torrelio M, Gershon S. Source: Psychopharmacol Commun. 1975; 1(3): 275-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1241452&dopt=Abstract
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Behavior modification for addicts on methadone maintenance. Author(s): Cheek FE. Source: Curr Psychiatr Ther. 1976; 16: 223-32. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081&dopt=Abstract
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Bridging the gap: the methadone client in 12-step programs. Author(s): Obuchowsky M, Zweben JE. Source: J Psychoactive Drugs. 1987 July-September; 19(3): 301-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3694335&dopt=Abstract
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Cerebral metabolism in opiate-dependent subjects: effects of methadone maintenance. Author(s): Galynker II, Watras-Ganz S, Miner C, Rosenthal RN, Des Jarlais DC, Richman BL, London E. Source: The Mount Sinai Journal of Medicine, New York. 2000 October-November; 67(56): 381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064488&dopt=Abstract
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Changes in locus-of-control attitudes about drug misuse in a self-help group in a methadone maintenance clinic. Author(s): Nurco DN, Primm BJ, Lerner M, Stephenson P, Brown LS, Ajuluchukwu DC. Source: Int J Addict. 1995 May; 30(6): 765-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7657402&dopt=Abstract
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Comparing Hatha yoga with dynamic group psychotherapy for enhancing methadone maintenance treatment: a randomized clinical trial. Author(s): Shaffer HJ, LaSalvia TA, Stein JP. Source: Alternative Therapies in Health and Medicine. 1997 July; 3(4): 57-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9210777&dopt=Abstract
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Correlates of benzodiazepine abuse in methadone maintenance treatment. A 1 year prospective study in an Israeli clinic. Author(s): Bleich A, Gelkopf M, Schmidt V, Hayward R, Bodner G, Adelson M. Source: Addiction (Abingdon, England). 1999 October; 94(10): 1533-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790905&dopt=Abstract
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Differentiation of long-term methadone patients from their admission cohorts. Author(s): Kotzker E, Steer RA, Schut J. Source: Int J Addict. 1979 February; 14(2): 281-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=447433&dopt=Abstract
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Evaluating outcome criteria used in methadone maintenance programs. Author(s): Cohen M, Howard A, Klein DF, Newfield K. Source: Int J Addict. 1976; 11(2): 283-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1262095&dopt=Abstract
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Group art therapy in a methadone clinic lobby. Author(s): Virshup E. Source: Journal of Substance Abuse Treatment. 1985; 2(3): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4094003&dopt=Abstract
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Health status at entry to methadone maintenance treatment using the SF-36 health survey questionnaire. Author(s): Ryan CF, White JM. Source: Addiction (Abingdon, England). 1996 January; 91(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8822013&dopt=Abstract
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Hyperbaric oxygen therapy for ischaemia of the hand due to intra-arterial injection of methadone and flunitrazepam. Author(s): Adir Y, Halpern P, Nachum Z, Bitterman H.
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Source: Eur J Vasc Surg. 1991 December; 5(6): 677-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1756884&dopt=Abstract •
Insomnia among addicts during supervised withdrawal from opiates: a comparison of oral methadone and electrostimulation. Author(s): Gossop M, Bradley B. Source: Drug and Alcohol Dependence. 1984 March; 13(2): 191-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6609807&dopt=Abstract
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Marijuana use by methadone maintenance patients. Author(s): Saxon AJ, Calsyn DA, Blaes PA, Haver VM, Greenberg DM. Source: Nida Res Monogr. 1991; 105: 306-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876021&dopt=Abstract
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Methadone and chemotherapy in drug addiction. Genocidal or lifesaving? Author(s): Chappel JN. Source: Jama : the Journal of the American Medical Association. 1974 May 6; 228(6): 7258. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4406260&dopt=Abstract
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Methadone Anonymous: A 12-Step Program for Methadone Maintained Heroin Addicts. Author(s): Gilman SM, Galanter M, Dermatis H. Source: Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse. 2001 December; 22(4): 247-256. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466684&dopt=Abstract
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Methadone anonymous: a 12-step program. Reducing the stigma of methadone use. Author(s): McGonagle D. Source: Journal of Psychosocial Nursing and Mental Health Services. 1994 October; 32(10): 5-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7844771&dopt=Abstract
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Methadone dose decreases and anxiety reduction. Author(s): Hall SM, Loeb PC, Kushner M. Source: Addictive Behaviors. 1984; 9(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6377843&dopt=Abstract
•
Methadone maintenance for opioid dependence. Author(s): Annitto WJ.
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Source: Jama : the Journal of the American Medical Association. 2000 August 9; 284(6): 694; Author Reply 694-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10927771&dopt=Abstract •
Methadone maintenance in pregnancy: a reappraisal. Author(s): Brown HL, Britton KA, Mahaffey D, Brizendine E, Hiett AK, Turnquest MA. Source: American Journal of Obstetrics and Gynecology. 1998 August; 179(2): 459-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9731853&dopt=Abstract
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Methadone maintenance treatment and drugs. Author(s): Bilban M, Bilban Jakopin C. Source: Coll Antropol. 2002 June; 26(1): 107-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137290&dopt=Abstract
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Methadone maintenance treatment and St. John's Wort - a case report. Author(s): Eich-Hochli D, Oppliger R, Golay KP, Baumann P, Eap CB. Source: Pharmacopsychiatry. 2003 January; 36(1): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649774&dopt=Abstract
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Methadone maintenance treatment at Sisters of Charity, Buffalo. Author(s): Dever MC, Boyd TJ Jr. Source: Hosp Prog. 1974 February; 55(2): 32-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4811513&dopt=Abstract
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Methadone maintenance-type treatment programs for alcoholics. Author(s): Rogers GA. Source: The American Journal of Psychiatry. 1971 September; 128(3): 366-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5571010&dopt=Abstract
•
Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine. Author(s): Stine SM, Grillon CG, Morgan CA 3rd, Kosten TR, Charney DS, Krystal JH. Source: Psychopharmacology. 2001 March; 154(3): 274-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351934&dopt=Abstract
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Methylphenidate (ritalin) abuse and methadone maintenance. Author(s): Raskind M, Bradford T. Source: Dis Nerv Syst. 1975 January; 36(1): 9-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1109888&dopt=Abstract
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Opioid receptor imaging with positron emission tomography and [(18)F]cyclofoxy in long-term, methadone-treated former heroin addicts.
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Author(s): Kling MA, Carson RE, Borg L, Zametkin A, Matochik JA, Schluger J, Herscovitch P, Rice KC, Ho A, Eckelman WC, Kreek MJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 December; 295(3): 1070-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082442&dopt=Abstract •
Outcomes of an AIDS prevention program for methadone patients. Author(s): Magura S, Siddiqi Q, Shapiro J, Grossman JI, Lipton DS, Marion IJ, Weisenfeld L, Amann KR, Koger J. Source: Int J Addict. 1991 June; 26(6): 629-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1757169&dopt=Abstract
•
Pattern of cocaine use in methadone-maintained individuals applying for research studies. Author(s): Levin FR, Foltin RW, Fischman MW. Source: J Addict Dis. 1996; 15(4): 97-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8943584&dopt=Abstract
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Prenatal administration of methadone in the rat: acoustic startle amplitude and the rest-activity cycle at 30 days of age. Author(s): Zmitrovich AC, Brake SC, Liu PY, Hamowy AS, Hutchings DE. Source: Neurotoxicology and Teratology. 1994 May-June; 16(3): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7935258&dopt=Abstract
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Pre-treatment characteristics, program philosophy and level of ancillary services as predictors of methadone maintenance treatment outcome. Author(s): Saxon AJ, Wells EA, Fleming C, Jackson TR, Calsyn DA. Source: Addiction (Abingdon, England). 1996 August; 91(8): 1197-209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828247&dopt=Abstract
•
Psychophysiological reactions in methadone maintenance patients do not correlate with methadone plasma levels. Author(s): Loimer N, Schmid R, Grunberger J, Jagsch R, Linzmayer L, Presslich O. Source: Psychopharmacology. 1991; 103(4): 538-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2062987&dopt=Abstract
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Self-detoxification attempts among methadone maintenance patients: what methods and what success? Author(s): Noble A, Best D, Man LH, Gossop M, Stang J. Source: Addictive Behaviors. 2002 July-August; 27(4): 575-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188593&dopt=Abstract
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Sex, drugs and HIV counseling and testing: a prospective study of behavior-change among methadone-maintenance clients in New England. Author(s): MacGowan RJ, Brackbill RM, Rugg DL, Swanson NM, Weinstein B, Couchon A, Scibak J, Molde S, McLaughlin P, Barker T, Voigt R. Source: Aids (London, England). 1997 February; 11(2): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9030371&dopt=Abstract
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Suicidality in a sample of methadone maintenance clients. Author(s): Chatham LR, Knight K, Joe GW, Simpson DD. Source: The American Journal of Drug and Alcohol Abuse. 1995 August; 21(3): 345-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7484984&dopt=Abstract
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The clinical effectiveness of electrostimulation vs oral methadone in managing opiate withdrawal. Author(s): Gossop M, Bradley B, Strang J, Connell P. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1984 February; 144: 203-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6608391&dopt=Abstract
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Towards a rehabilitation of methadone maintenance: integration of relapse prevention and aftercare. Author(s): Weddington WW. Source: Int J Addict. 1990-91 August; 25(9A-10A): 1201-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1966683&dopt=Abstract
•
Treatment of methadone withdrawal with cerebral electrotherapy (electrosleep). Author(s): Gomez E, Mikhail AR. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1979 January; 134: 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=760910&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
•
Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON METHADONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to methadone. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “methadone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on methadone, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Methadone ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to methadone. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Comparison of African-american and White Male Drug Addicts in Methadone Maintenance Treatment Programs: the Role of Social Causality in the Development of Addiction by Gilbert, James, Phd from New York University, 1998, 127 pages http://wwwlib.umi.com/dissertations/fullcit/9833857
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A Harm Reduction Intervention Following Methadone Treatment Discharge: Enhanced Outreach Counseling by Zanis, David Anthony, Phd from University of Pennsylvania, 1996, 176 pages http://wwwlib.umi.com/dissertations/fullcit/9628035
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A Self-concept Analysis of Heroin Addicts, Drug-free Ex-addicts, and Methadone Maintenance Patients by Porteus, James Hewins, Edd from University of Northern Colorado, 1972, 82 pages http://wwwlib.umi.com/dissertations/fullcit/7300305
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A Social Ecology of Methadone Maintenance Treatment: Organizational Compliance and Involvement of Injection Drug Users by Kelley, Margaret Sue, Phd from New York University, 1999, 360 pages http://wwwlib.umi.com/dissertations/fullcit/9917054
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A Study of Ex-heroin Addicts in a Methadone Treatment Program and Their Employability. by Pugliese, Anthony Charles, Edd from Rutgers the State University of New Jersey - New Brunswick, 1974, 164 pages http://wwwlib.umi.com/dissertations/fullcit/7427338
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A Study of the Interaction between Counseling and Methadone in the Treatment of Narcotic Addiction. by Weiner, Harvey David, Dsw from University of Pennsylvania, 1974, 189 pages http://wwwlib.umi.com/dissertations/fullcit/7423036
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An Analysis of Employment Patterns among a Cohort of Methadone Maintenance Patients. by Rothenberg, Pearila Brickner, Phd from Columbia University, 1976, 241 pages http://wwwlib.umi.com/dissertations/fullcit/7708264
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An Economic Analysis of the Methadone Maintenance Treatment Program. by Backhaut, Bernard Herman, Phd from City University of New York, 1976, 130 pages http://wwwlib.umi.com/dissertations/fullcit/7618402
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An Examination of the Impact on Drug Addicts of Professional Vs. Paraprofessional Counselors in Effecting Change in Self Concept and Attitude toward the Counselor during Six Months in a Methadone Maintenance Therapeutic Program by Taitz, Yaakov, Phd from New York University, 1980, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8027492
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An Exploratory Study of Heroin Addiction among White, Middle-class Male Addicts Receiving Methadone Maintenance Treatment by Platt, Joshua Paul, Phd from University of Pittsburgh, 1985, 167 pages http://wwwlib.umi.com/dissertations/fullcit/8517994
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An Intense Study by Interview of Methadone Treated African-american Patients (methadone Treatment, Drug Addiction) by Hodges, James Elmer, Phd from The Union Institute, 1991, 186 pages http://wwwlib.umi.com/dissertations/fullcit/9217640
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Assessment of the Emittm Technique As a Screening Test for Opiates and Methadone for a Methadone Maintenance Clinic and Its Calibration by Bayesian Statistics; Purification of Bovine and Human Alkaline Phosphatases and Preliminary Investigations of Cross by Cavanagh, Kevin Thomas; Phd from University of Windsor (canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK41934
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Change in Locus of Control, Anxiety, Depression and Social Behavior As a Function of Time in Methadone Maintenance Therapy by Hanbury, Raymond Francis Jr., Phd from New York University, 1980, 198 pages http://wwwlib.umi.com/dissertations/fullcit/8017503
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Childhood Sexual Abuse and Partner Violence among Women in Methadone Treatment: Mediating and Causal Effects of Mental Health and Substance Use Factors by Engstrom, Malitta Victoria; Phd from Columbia University, 2002, 142 pages http://wwwlib.umi.com/dissertations/fullcit/3048126
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Differential Diagnosis of Women in Drug Treatment: Methadone or Menopause by Tuchman, Ellen Lee; Phd from New York University, 2003, 198 pages http://wwwlib.umi.com/dissertations/fullcit/3073504
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Education Program of a Community Methadone Maintenance Center. by King, Edward Leonard, Jr., Edd from Wayne State University, 1974, 97 pages http://wwwlib.umi.com/dissertations/fullcit/7429821
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Effects of a Rehabilitation Program Including Group-counseling on the Personality Constructs of Internal-external Control of Patients in a Methadone Treatment Program by Mehr, Lois Marilyn, Phd from University of Southern California, 1972, 154 pages http://wwwlib.umi.com/dissertations/fullcit/7300753
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Effects of Personal Costs of Methadone Maintenance, Especially Time Price, on Treatment Attendance by Borisova, Natalia N. Phd from Wayne State University, 2000, 113 pages http://wwwlib.umi.com/dissertations/fullcit/9992163
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Ex-addicts against the Labor Market: a Study of the Labor Market Experience of Men Enrolled in the New York City Methadone Maintenance Treatment Program. by Menzi, Donald Wilder, Phd from New York University, 1977, 184 pages http://wwwlib.umi.com/dissertations/fullcit/7803118
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Exploring the Experiences of Women Enrolled in Methadone Maintenance Treatment by Gibson, Cassandra Crawford; Phd from University of Maryland, Baltimore, 2002, 275 pages http://wwwlib.umi.com/dissertations/fullcit/3048444
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Identification of Factors Associated with the Employment Characteristics of Methadone Clients: Targeting Vocational Services (drug Abuse) by Metzger, David Scott, Phd from Rutgers the State University of New Jersey - New Brunswick, 1987, 165 pages http://wwwlib.umi.com/dissertations/fullcit/8723272
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'liquid Handcuffs': the Phenomenology of Recovering on Methadone Maintenance by Vigilant, Lee Garth; Phd from Boston College, 2001, 333 pages http://wwwlib.umi.com/dissertations/fullcit/3008911
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Locus of Control and Heroin Addiction in a Methadone Maintenance Setting by Heinbach, Henry, Dsw from Yeshiva University, 1996, 203 pages http://wwwlib.umi.com/dissertations/fullcit/9638327
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Medical Methadone Maintenance: the Further Concealment of a Stigmatized Condition by Joseph, Herman, Phd from City University of New York, 1995, 292 pages http://wwwlib.umi.com/dissertations/fullcit/9530884
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Methadone Hydrochloride Effects of Acute Administration on Disposition and Hepatic Functions in Adult and Perinatal Guinea Pigs by Pak, Raphael C. K; Phd from Mcgill University (canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK52066
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Methadone Maintenance and Crime (drug Addiction) by Spunt, Barry J., Phd from Fordham University, 1990, 293 pages http://wwwlib.umi.com/dissertations/fullcit/9025025
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Methadone Maintenance: Issues in Drug Policy. by Klein, Dorothy Anita, Dcrim from University of California, Berkeley, 1979, 468 pages http://wwwlib.umi.com/dissertations/fullcit/8000249
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Methadone Maintenance: a Systematic Analysis of the Relationship between Prior Patient Characteristics, the Clinical Treatment Process, and Rehabilitative Success. by Meints, Jerold Roy, Phd from University of California, Riverside, 1978, 186 pages http://wwwlib.umi.com/dissertations/fullcit/7814063
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Motivation for Drug Abuse Treatment and Retention Rates in Standard and Enhanced Methadone Maintenance Programs by Marin, Mary Elizabeth, Phd from University of California, Los Angeles, 1995, 176 pages http://wwwlib.umi.com/dissertations/fullcit/9608060
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Motivational Enhancement Therapy for Cigarette Smoking in Methadone-maintained Pregnant Women by Haug, Nancy Anne; Phd from University of Maryland Baltimore County, 2002, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3062585
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Object Relations, Alexithymia, Symptoms of Psychological Distress and Methadone Treatment Outcome by Wood, Starr A. Phd from Smith College School for Social Work, 2000, 167 pages http://wwwlib.umi.com/dissertations/fullcit/9974847
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Patterns of Death in a Methadone-maintained Veterans Population by Norman, Reuben Lamar, Jr. Phd from City University of New York, 1994, 164 pages http://wwwlib.umi.com/dissertations/fullcit/9510697
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Patterns of Death in a Methadone-maintained Veterans Population by Norman, Rueben Lamar, Jr., Phd from City University of New York, 1994, 164 pages http://wwwlib.umi.com/dissertations/fullcit/9510697
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Patterns of Multiple Drug Abuse in Methadone-maintained Heroin Addicts by Smith, Thomas M., Phd from Rutgers the State University of New Jersey - New Brunswick, 1986, 119 pages http://wwwlib.umi.com/dissertations/fullcit/8612137
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Policy Translation: the Political Translation of Methadone Maintenance Treatment and Family Doctors in Sweden by Johnson, Bjorn; Phd from Lunds Universitet (sweden), 2003, 276 pages http://wwwlib.umi.com/dissertations/fullcit/f165361
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Rationalities of Risk: Intimate Action in the Age of Aids among Men on Methadone (immune Deficiency) by Fontdevila, Jorge; Phd from Columbia University, 2002, 193 pages http://wwwlib.umi.com/dissertations/fullcit/3037702
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Relationship of Time in Methadone Maintenance Treatment to Drug Use History and Social Participation by Stauder, John Walter, Dsw from The Catholic University of America, 1981, 189 pages http://wwwlib.umi.com/dissertations/fullcit/8129544
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Social Adaptation of Methadone Patients. by Kern, Diane Louise, Dcrim from University of California, Berkeley, 1977, 249 pages http://wwwlib.umi.com/dissertations/fullcit/7812450
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Stage of Change, Self-efficacy, Aids Knowledge, Perceived Risk and Actual Risk for Hiv Acquisition or Transmission among High-risk Methadone Clients (immune
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Deficiency) by Cohen, Sandra E. Edd from Columbia University Teachers College, 1999, 136 pages http://wwwlib.umi.com/dissertations/fullcit/9939471 •
Synthesis and Applications of Deuterated Methadone and Metabolites to Biotransformation and Disposition Studies by Kang, Gun-il; Phd from The University of British Columbia (canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK59243
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Targeting Hiv Risk Prevention Activities among Injection Drug Users in Needle Exchange, Methadone Maintenance, and Detoxification Programs in Philadelphia (pennsylvania) by Mark, Hayley Diana; Phd from University of Pennsylvania, 2002, 117 pages http://wwwlib.umi.com/dissertations/fullcit/3043910
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The Economics of Methadone Maintenance. by Hannan, Timothy Hale, Phd from The University of Wisconsin - Madison, 1974, 298 pages http://wwwlib.umi.com/dissertations/fullcit/7427740
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The Effects of a Behavioral Contingency Management Approach on Treatment Success in a Veterans Administration Medical Center Methadone Maintenance Outpatient Program by Feiner, Arnold Lester, Phd from University of Miami, 1979, 247 pages http://wwwlib.umi.com/dissertations/fullcit/8014167
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The Effects of Conflicting Treatment Approaches on the Operations and Procedures of Two Types of Methadone Treatment Programs: a Study in Institutional Analysis (organizational Theory, Detoxification, Drug Abuse) by Rainone, Gregory Anthony, Phd from Fordham University, 1985, 378 pages http://wwwlib.umi.com/dissertations/fullcit/8521413
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The Effects of Intrauterine Exposure to Heroin and Methadone on Child Motor Development and Learning Potential. by Hale, Lorraine Elisabeth, Edd from New York University, 1978, 129 pages http://wwwlib.umi.com/dissertations/fullcit/7818156
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The Effects of Methadone on Short-term Memory in the Rat by Fratzke, Mark Conrad; Phd from University of Hawaii, 2002 http://wwwlib.umi.com/dissertations/fullcit/f876049
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The Mmpi As a Predictor of Outcome in a Methadone Maintenance Program. by Ottomanelli, Gennaro Anthony, Phd from New York University, 1974, 133 pages http://wwwlib.umi.com/dissertations/fullcit/7412858
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Thietane 1,1-dioxides As Potential Analgetics of the Methadone Type by Leung, Chun-cheung; Phd from The University of British Columbia (canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK40680
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Thietane L,l-dioxide Derivatives As Potential Analgetics of the Methadone Type by Coates, James Everett; Phd from The University of British Columbia (canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK11213
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Treatment Outcome among Methadone Recipients: Influence of Perceived Social Support and Orientation towards Social Support by Smith, Jennifer Loretta; Phd from Mcp Hahnemann University, 2002, 114 pages http://wwwlib.umi.com/dissertations/fullcit/3041286
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Treatment Response to Methadone Maintenance and Its Relationship to Object Relationship Functioning by Nicholson, Barbara Louise, Dsw from Smith College School for Social Work, 1980, 212 pages http://wwwlib.umi.com/dissertations/fullcit/8028591
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND METHADONE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning methadone.
Recent Trials on Methadone The following is a list of recent trials dedicated to methadone.8 Further information on a trial is available at the Web site indicated. •
HIV Counseling Intervention for Methadone-Maintained Patients - 2 Condition(s): Opioid-Related Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: HIV Counseling Intervention for Methadone-Maintained Patients Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061100
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Treatment of Adult ADHD in Methadone Patients - 1 Condition(s): Opioid-Related Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: Treatment of Adult ADHD in Methadone Patients Phase(s): Phase I Study Type: Interventional
8
These are listed at www.ClinicalTrials.gov.
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061087 •
A Study to Assess the Effect of Concomitant Administration of Fluconazole on the Clinical Pharmacokinetics of Methadone Condition(s): Candidiasis; HIV Infections Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: To evaluate the pharmacokinetics and safety of concomitant administration of methadone and fluconazole. Injection drug users constitute the second largest subset of the U.S. population at risk for HIV infection and AIDS-associated mortality. Narcotic addiction is often treated by use of methadone. Fluconazole has been shown to be highly effective in treating symptomatic mucosal candidiasis, but it is unknown whether fluconazole affects methadone metabolism, which could result in symptoms of methadone withdrawal or overdose in patients taking the drugs in combination. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000788
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Effect Of Case Management Following Discharge From Methadone Treatment Condition(s): Opioid-Related Disorders Study Status: This study is no longer recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The purpose of this project is to assess whether enhanced outreach counseling (EOC) is an effective outreach strategy for discharged methadone maintenance patients compared to a standard referral procedure. EOC is a brief (30 minute) face-to-face intervention, followed by six weeks of ongoing telephone counseling/case management designed to help eligible out-of-treatment methadone patients re-enter treatment. Several studies have shown those patients who voluntarily re-enter treatment improve significantly following re-enrollment. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018226
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Herbal Treatment of Hepatitis C in Methadone Maintained Patients Condition(s): Hepatitis C Study Status: This study is no longer recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: Hepatitis C (HCV) is a chronic viral illness leading to progressive liver damage that has emerged as a major public health issue in the United States. While
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HCV affects all population groups, individuals with a history of intravenous drug use form the largest known risk group. Between 90 and 100 percent of long term intravenous drug use will eventually test positive for HCV, and there is substantial risk that even short term experimentation will result in infection. Studies suggest that HCV will be the major cause of cirrhosis and liver cancer in the next century. Currently, approved therapy includes recombinant interferons, which lead to sustained remission in a minority of patients. However, patients abusing other substances, including alcohol, are not eligible for interferon therapy. The need for investigation into other potential therapies is clear. Current practice patterns in the Far East include the use of traditional herbal remedies for symptomatic chronic viral hepatitis. This study is intended to examine the effect of commonly used herbal remedies for the treatment of symptomatic HCV. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010816 •
Motivational Incentives for Enhanced Drug Abuse Recovery: Methadone Clinics - 1 Condition(s): Substance-Related Disorders Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: Motivational Incentives for Enhanced Drug Abuse Recovery: Methadone Clinics. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033020
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A Study of Azidothymidine Plus Methadone in Patients with AIDS and AIDS Related Complex (ARC) Condition(s): HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: To determine if methadone treatment will affect the blood levels of zidovudine (AZT) in patients with AIDS or AIDS-related complex (ARC) who are receiving oral AZT and methadone therapy. In addition, the blood levels of methadone both before and during AZT treatment will be studied, and patients receiving daily oral methadone treatment will be evaluated for signs of narcotic withdrawal during treatment with AZT. The number of deaths due to AIDS in high-risk populations continues to increase. Nationwide approximately 25 percent of AIDS patients are intravenous (IV) drug abusers, and it is very likely that an increasingly larger number of AIDS patients receiving AZT therapy will have had a history of IV drug abuse. The major chemical treatment for IV drug abuse is daily methadone maintenance therapy, and IV drug abusers who are HIV positive represent a large number of patients who
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will undergo long-term treatment with both methadone and AZT. Therefore, the study of potential drug interactions is essential. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001008 •
Effects of Dextromethorphan on Opioid Tolerance in Methadone Patients - 1 Condition(s): Opioid-Related Disorders; Substance-Related Disorders Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Pennsylvania Purpose - Excerpt: To determine if addition of dextromethorphan to a stable dose of methadone in opioid dependent subjects will significantly affect physical and psychological aspects of opioid tolerance. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000352
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Interactions of HIV Protease Inhibitors and Methadone in HIV-Infected Patients Condition(s): HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if it is safe to combine methadone with two HIV protease inhibitors (PIs), ritonavir (RTV) and saquinavir (SQV), in HIVinfected patients not currently taking PIs. This study will measure the interactions between methadone and the PIs. Methadone is used treat addicts and to treat severe pain. In order to find the safest way to use methadone with PIs, it is important to evaluate how they interact. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000906
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Methadone Effects on Zidovudine (ZDV, AZT) Disposition Condition(s): HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Glaxo Wellcome Purpose - Excerpt: To determine whether methadone maintenance alters the pharmacokinetics of zidovudine (AZT). To determine whether any such effect of methadone on disposition of AZT is time dependent and whether a metabolic interaction between AZT and methadone exists. Injection drug users represent an
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increasing proportion of HIV-infected persons. Since daily methadone maintenance is the major chemical treatment for injection drug abuse, it is important to determine the impact of methadone on AZT absorption, distribution, and elimination. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000800 •
METHADONE, BUPRENORPHINE AND FETAL DEVELOPMENT - 1 Condition(s): Methadone Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute on Drug Abuse (NIDA); Johns Hopkins University Purpose - Excerpt: 1. Fetal Neurobehavior of Methadone Maintained Women at Peak vs. Trough Plasma Levels at EGA 30+Weeks Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067184
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Methadone/Buprenorphine Cross-over Study - 4 Condition(s): Opioid-Related Disorders Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA) Purpose - Excerpt: Explore ways to cross patients over from methadone to buprenorphine. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000208
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Pharmacokinetics of LAAM in Methadone Patients - 5 Condition(s): Opioid-Related Disorders; Substance-Related Disorders Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); University of Pennsylvania Purpose - Excerpt: To determine the pharmacokinetics of LAAM in adult males and females transferred from methadone maintenance treatment for opiate dependence. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000356
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Pharmacological Comparison of Buprenorphine and Methadone - 3 Study Status: This study is completed. Sponsor(s): National Institute on Drug Abuse (NIDA); VA-Washington, DC Purpose - Excerpt: To compare agonist and antagonist profile associated with buprenorphine vs. methadone during opiate withdrawal. Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000334
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “methadone” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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•
For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. BOOKS ON METHADONE Overview This chapter provides bibliographic book references relating to methadone. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on methadone include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “methadone” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on methadone: •
Chemical Dependency and AIDS Source: Acquired Immune Deficiency Syndrome and Chemical Dependency. Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. Summary: Although the fear of AIDS has dramatically modified behavior patterns of homosexuals, lifestyles of IV drug abusers has not changed much; consequently, those people have the highest risk of contracting AIDS. Workers in the chemical dependency field work toward abstinence and recovery-oriented treatment but social policy, in the form of methadone maintenance clinics and free needles and syringes, is going in the opposite direction. The use of drugs, while not a causative factor for AIDS, is a co-factor in many cases. Clincal studies indicate that a change to a healthier social and sexual lifestyle can reduce the progression from seropositivity to ARC or AIDS.
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Killing the Ill? Heroin and AIDS in West Germany Source: Drug Policies in Western Europe. Contact: Max - Planck - Institut, Gunterdstalstrabe 73, Freiburg. Summary: This book chapter debates the merits of the Federal Republic of Germany's policy against methadone treatment for heroin users. The writer points out that although methadone treatment has proven extremely successful in other Western nations, allowing heroin addicts to break their injection habits and live healthier, more productive lives, the FRG government remains opposed to the treatment plan. The book chapter says that this not only condemns the Intravenous drug users (IVDU's) to less fulfilling lives and eventual death, it also contributes to the spread of Acquired immunodeficiency syndrome (AIDS). This happens in two ways: One, because more people are using needles, there are more people to share needles; and two, IVDU's on methadone prove more receptive to Human immunodeficiency virus (HIV) prevention information.
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Project BRAVO: A Boroughwide Effort in the Bronx Source: Simple Acts of Kindness; Volunteering in the Age of AIDS. Contact: United Hospital Fund of New York, Publications Program, 55 5th Ave 16th Fl, New York, NY, 10003, (212) 645-2500. Summary: This book chapter describes the development of a volunteer program as a joint effort of by volunteers and municipal hospitals. It focuses on a methadone clinic for Intravenous drug users (IVDU's) who have tested positive for Human immunodeficiency virus (HIV), which uses Persons with AIDS (PWA's) as volunteers. It describes the recruitment, screening, training, support, supervision, and referral and assignment components of the Bronx AIDS Volunteer Organization (BRAVO) Program.
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Counseling Chemically Dependent People With HIV Illness Contact: Haworth Press, Incorporated, Harrington Park Press, Incorporated, 12 W 32 St, New York, NY, 10001, (212) 563-4247. Summary: This book describes clinical counseling of chemically dependent persons with HIV infection. Several case studies illustrate problems in treatment and different solutions to these problems. The first chapter is narrated by a 52-year-old homosexual man who describes his case history of addiction, recovery, and coping with AIDS. The second of 13 chapters gives medical information about HIV. The next three chapters address counseling adolescents, working with inpatients, and providing short-term group work in a hospital setting. Methadone maintenance is the subject of the next chapter, followed by chapters on treatment issues surrounding specific groups such as homosexual men, Native Americans, and prisoners. The final four chapters consider the use of outpatient psychotherapy, residential treatment, the harm-reduction model of HIV prevention, and countertransference in professionals with chemically dependent clients with HIV infection.
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Drug dependency in pregnancy: Managing withdrawal Source: [Sacramento, CA]: Maternal and Child Health Branch, California Department of Health Services. 1992. 322 pp.
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Contact: Available from Publications Section, California Department of General Services, P.O. Box 1015, North Highland, CA 95660. Telephone: (916) 973-3700. $12.90; make check payable to the State of California. Summary: This book is about the medical management of withdrawal from drugs in the pregnant addicted woman. It discusses drug use in the perinatal patient and the subsequent exposure and risk to the woman, fetus, and the newborn. It emphasizes safe, managed drug withdrawal to enhance maternal and infant outcomes. Chapters cover methadone maintenance, withdrawal in the pregnant alcoholic, benzodiazepines and other sedatives, cocaine, and smoking cessation. Other chapters focus on fetal and neonatal issues, and legal, ethical, and advocacy issues. •
AIDS Outreach in the Community: National Institute on Drug Abuse Directory on Community Outreach Demonstration Projects and National Resource Organizations Contact: ROW Sciences, Incorporated, Drug Use and AIDS Community Education Technical Assistance, Project, 5515 Security Ln Ste 500, Rockville, MD, 20852, (301) 7706070. Summary: This directory provides a State-by-State list of recipients of grants and contracts from the National Institute on Drug Abuse (NIDA) to conduct AIDS comprehensive community grants and target outreach demonstration projects. Entries list organization names, addresses and telephone numbers; principal and coinvestigators; project directors; training coordinators; model numbers; NIDA contract numbers; Federal Project Officers; and Row Sciences contacts. A second list arranges the AIDS targeted outreach demonstration contracts by model. Models include: 1) Outreach to sexual partners and prostitutes; 2) outreach to emergency rooms and detoxification units; 3) indigenous leader outreach; 4) increasing capability or methadone maintenance programs; 5) outreach to therapeutic community contacts and clients; 6) AIDS outreach/pregnant women and their children; 7) AIDS outreach for arrested drug abusers; and 8) AIDS outreach to public housing projects. A third lists cites national organizations that provide services, materials, and information related to HIV prevention and education and Federal programs under the U.S. Department of Health and Human Services and the Public Health Service, and private and professional organizations.
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Ohio AIDS Information and Health Care Resources Directory Contact: Ohio Department of Health, Division of Preventive Medicine, HIV/STD Prevention Program, 246 N High St Box 118, Columbus, OH, 43215-2412, (614) 644-1838, http://www.odh.state.oh.us/ODHPrograms/HIVSTD/hivstd1.htm. Summary: This directory provides sources of information about Human immunodeficiency virus (HIV) infection and Acquired immunodeficiency syndrome (AIDS), with emphasis on resources in Ohio. The listed resources deal with the prevention and treatment of various stages of HIV infection. Information sources include local health departments and local AIDS task forces. The resources are grouped into the following categories: Counseling and testing sites, task forces and related organizations, telephone sources of AIDS information, national hotlines and information resources, and licensed Ohio methadone treatment programs. Information is also given on Ohio's AIDS waiver program and the Azidothymidine (AZT) emergency fund. A county-by-county listing gives the addresses and telephone numbers of health departments, medical services, social services, legal referrals, support groups, blood
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banks, and related organizations. Members of the AIDS Activities Unit and the AIDS Advisory Committee of the Ohio Department of Health are also listed. •
Effects of Substance Abuse Treatment on AIDS Risk Behaviors Contact: Haworth Press, 10 Alice Street, Binghamton, NY, 13904-9981, (800) 342-9678. Summary: This monograph contains one editorial, six research articles, and one discussion article concerning the role of drug abuse treatment as a potentially powerful means of preventing the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS): (1) Editorial: The Problem of HIV/AIDS as Related to Drug Abuse: An Introduction; (2) Drug Abuse Treatment as HIV Prevention: Changes in Social Drug Use Patterns Might Also Reduce Risk; (3) Stimulant Abuse Treatment as HIV Prevention; (4) AIDS Risk Behavior in Opioid Dependent Patients Treated with Community Reinforcement Approach and Relationships with Psychiatric Disorders; (5) Assessment of HIV Risk; (6) Does Intensive Outpatient Cocaine Treatment Reduce AIDS Risky Behavior?; (7) Changes in HIV Risk Behaviors Among Cocaine-Using Methadone Patients; and (8) HIV/AIDS and Drug Abuse: Epidemiology and Prevention. The monograph also includes a selected guide to current reference sources on topics discussed in the monograph.
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Epidemiology of HIV Infection Among Drug Users in Amsterdam Contact: Department of Public Health and Environment, Drugs Department of the Municipal Health Service, of Amsterdam, Amsterdam. Summary: This monograph discusses a study started at the end of 1985 to investigate the incidence and prevalence of HIV infection among drug users in Amsterdam, in relation to changes in drug use and sexual behavior. The voluntary participants were injection (IDU) and non-injection drug users recruited from methadone outpatient clinics and sexually transmitted disease (STD) clinics for drug-using sex workers. They responded to a questionnaire concerning their clinical symptoms, medical history, lifestyle, use of oral drugs, IV-drug use, and sex work. The chapters of the monograph are presented as separate articles discussing the following aspects of the study: 1) prevalence and risk factors of HIV infection among drug users; 2) HIV and STD's in drug-using sex workers and the potential for heterosexual transmission, in relation to sexual practices and condom use with clients; 3) heterosexual behavior of IV drug users, and the implications for HIV transmission; and 4) changes in IV drug use over time, in relation to knowledge of HIV antibody status. Two chapters trace the relationship between risk reduction and lower incidences of HIV in the study population. The estimated incidence of hepatitis B among drug users in Amsterdam and the incidence of hepatitis C in the study cohort are examined as surrogate markers for HIV infection. The final chapter discusses the findings of the study in relation to current epidemiologic data and preventive strategies.
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Drug Abuse Treatment in Prisons and Jails Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. Summary: This monograph presents a collection of papers examining treatment of drug abuse and dependence among incarcerated populations. It is based on the papers from a technical review on "Drug Abuse Treatment in Prisons and Jails", sponsored by the National Institute on Drug Abuse (NIDA) in 1990. The papers discuss issues of program effectiveness, voluntary participation versus programs based on legal sanctions, and
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evaluation methods. Models, designs and evaluations of prerelease and aftercare programs are analyzed, including Federal initiatives, a Wisconsin demonstration program, and programs in Delaware, Florida, and Oregon. Other papers address the following topics: HIV-1 infection in the correctional setting, evaluation of in-jail methadone maintenance, and management of the drug-abusing offender. •
Cocaine, AIDS and Intravenous Drug Use Contact: Haworth Press, Incorporated, Harrington Park Press, Incorporated, 12 W 32 St, New York, NY, 10001, (212) 563-4247. Summary: This monograph presents the text of seven clinical papers on the connection between cocaine, injection drug use, and HIV/AIDS. The papers start off with one that looks at present trends and future directions in pharmacotherapeutic treatment for cocaine addiction. The second looks at how methadone treatment changes cocaine use, while the third studies cardiovascular evaluation after withdrawal from chronic abuse of alcohol, or alcohol and cocaine. In the fourth paper, the monograph looks at drug treatment programs aimed at preventing HIV transmission. The fifth examines a pilot syringe exchange program in Tacoma, WA. The sixth paper explores new approaches to HIV prevention for injecting drug users (IDUs), while the final paper studies why female sex partners of IDUs continue to remain at high risk for HIV.
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Behavioral Treatments for Drug Abuse and Dependence Contact: National Clearinghouse for Alcohol and Drug Information, Substance Abuse and Mental Health Service Administration, PO Box 2345, Rockville, MD, 20852-2345, (301) 468-2600, http://www.health.org. US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. Summary: This monograph reviews technical papers on the application of behavior treatment; methadone treatment; behavioral interventions; cure reactivity; cocaine dependence; cognitive therapy; harm reduction; multisystemic treatment of serious juvenile offenders; dialectical behavior therapy; substance abuse research; and clinical trials.
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AIDS Prevention in the Netherlands: Intravenous Drug Users As a Target Group Source: AIDS and Prevention and Control, Invited Presentations and Papers From the World Summit of Ministers of Health on Programmes for AIDS Prevention; London, January 26-27, 1988. Contact: Pergamon Press, 660 White Plains Rd, Tarrytown, NY, 10591, (914) 524-9200. Summary: This presentation was given at the World Summit of Ministers of Health on Programmes for AIDS Prevention held in London, January 26-27, 1988. The summit was jointly organized by the World Health Organization and the United Kingdom Government. With the cooperation of drug users and health care and social workers, new Acquired immunodeficiency syndrome (AIDS) prevention strategies have been incorporated into municipal programs for intravenous drug users in Amsterdam, Netherlands. The program has four objectives: outreach and regular contact with drug addicts on street corners and at police stations; harm reduction through the provision of information on safer and unsafe sexual practices and distribution of condoms; easy access to health care facilities for drug-free treatment and methadone distribution; and counseling.
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The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “methadone” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:9 •
Community implications of methadone use in treating heroin addiction; a technical guide. Author: Public Technology, inc.; Year: 1974; Washington, 1973
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Federal and state laws pertaining to methadone Author: Cobb, J. C.; Year: 1975; Rockville, Md.: National Institute on Drug Abuse, 1975
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Medical evaluation of long-term methadone-maintained clients Author: Kleber, Herbert D.; Year: 1986; Rockville, Md.: U.S. Dept. of Health and Human Services, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute on Drug Abuse, 1980 printing
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Methadone: benefits and shortcomings Author: Bourne, Peter G.,; Year: 1977; Washington: Drug Abuse Council, 1975
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Methadone and pregnancy. Author: Student Association for the Study of Hallucinogens.; Year: 1971; Rockville, Md., National Institute on Drug Abuse; [for sale by the Supt. of Docs., U. S. Govt. Print. Off., Washington, 1974]
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Methadone maintenance treatment in New York City Author: Todd, Suzanne W.; Year: 1977; New York: Community Service Society of New York, c1975
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Methadone maintenance, edited by Stanley Einstein. Author: Einstein, Stanley.; Year: 1974; New York, Dekker, 1971; ISBN: 0824711653 http://www.amazon.com/exec/obidos/ASIN/0824711653/icongroupinterna
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Methadone maintenance: a technological fix. Author: Nelkin, Dorothy.; Year: 1973; New York, Braziller [c1973]; ISBN: 0807606812 http://www.amazon.com/exec/obidos/ASIN/0807606812/icongroupinterna
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Methadone maintenance: the experience of four programs. Author: Danaceau, Paul.; Year: 1973; [Washington] 1973
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Methadone program Author: New York (State). Legislature. Legislative Commission on Expenditure Review.; Year: 1981; Albany, N.Y.: The Legislature, State of New York, [1981?]
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Methadone treatment in narcotic addiction: program management, findings, and prospects for the future Author: Newman, Robert G.,; Year: 1977; New York: Academic Press, 1977; ISBN: 0125170505 http://www.amazon.com/exec/obidos/ASIN/0125170505/icongroupinterna
9
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Methadone treatment manual. Author: National Institute of Law Enforcement and Criminal Justice.; Year: 1973; Washington, For sale by the Supt. of Docs., U. S. Govt. Print. Off., 1963
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Methadone use and abuse - 1972 Author: United States. Congress. Senate. Committee on the Judiciary. Subcommittee to Investigate Juvenile Delinquency.; Year: 1975; Washington, U. S. Govt. Print. Off., 1973
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Methadone: experiences and issues. Edited by Carl D. Chambers [and] Leon Brill. Author: Chambers, Carl D.; Year: 1973; New York, Behavioral Publications, 1973; ISBN: 0877050724 http://www.amazon.com/exec/obidos/ASIN/0877050724/icongroupinterna
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More effective action needed to control abuse and diversion in methadone treatment programs: Food and Drug Administration, Department of Health, Education, and Welfare, Drug Enforcement Administration, Department of Justice: report to Congress Author: United States. General Accounting Office.; Year: 1975; Washington: U. S. General Accounting Office, 1976
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Outpatient methadone treatment manual. Author: United States. Special Action Office for Drug Abuse Prevention.; Year: 1968; [Washington]: Executive Office of the President, Special Action Office for Drug Abuse Prevention, 1974
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Oversight --methadone maintenance program, Buffalo, N. Y. Hearing... Ninety-second Congress, second session on methadone and the method of treatment for heroin addicts in the Buffalo, N. Y. area, March 23, 1972. Author: United States. Congress. House. Committee on Interstate and Foreign Commerce. Subcommittee on Public Health and Environment.; Year: 1973; Washington, U. S. Govt. Print. Off., 1972
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Psychotherapy for methadone maintained opiate addicts: a report of two studies. Author: National Institute on Drug Abuse.; Year: 1974; Rockville, Md.: U.S. Dept. of Health and Human Services, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, 1983
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Regulation of methadone and other narcotic drugs in treatment programs. Hearings... Ninety-third Congress, first session on H. R. 4872, H. R. 623, H. R. 4633, H. R. 7643, H. R. 8685 and S. 1115,... June 18 and 27, 1973. Author: United States. Congress. House. Committee on Interstate and Foreign Commerce. Subcommittee on Public Health and Environment.; Year: 1973; Washington, U. S. Govt. Print. Off., 1973
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Security controls for methadone distribution need improving: Department of Justice, Department of Health, Education and Welfare Author: United States. General Accounting Office.; Year: 1976; [Washington: U. S. General Accounting Office, 1975]
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The economics of methadone maintenance Author: Hannan, Timothy H.; Year: 1975; Lexington, Mass.: Heath, c1975; ISBN: 0669992593 http://www.amazon.com/exec/obidos/ASIN/0669992593/icongroupinterna
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Therapeutic effectiveness of methadone maintenance programs in the management of drug dependence of morphine type in the USA [by] Stephen S. Wilmarth and Avram Goldstein. Author: Wilmarth, Stephen S.; Year: 1974; Geneva, World Health Organization, 1974; ISBN: 9241700033 http://www.amazon.com/exec/obidos/ASIN/9241700033/icongroupinterna
Chapters on Methadone In order to find chapters that specifically relate to methadone, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search
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to book chapters and methadone using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “methadone” (or synonyms) into the “For these words:” box.
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CHAPTER 7. MULTIMEDIA ON METHADONE Overview In this chapter, we show you how to keep current on multimedia sources of information on methadone. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on methadone is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “methadone” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “methadone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on methadone: •
Points to Change Contact: Gay Mens Health Crisis, 119 W 24th St Tisch Bldg, New York, NY, 10011-1995, (212) 367-1205, http://www.gmhc.org. Summary: This videorecording focuses on the philosophy and practice of ear point acupuncture. Practitioners and patients discuss acupuncture's applicability in a variety of community settings, including drug treatment, needle exchange, and AIDS services. The film features Michael Smith, M.D., D.Ac., Director of the Substance Abuse Institute, Lincoln Hospital in Bronx, NY, relating theories of acupuncture to drug treatment. Other practitioners point out that acupuncture helps them be more patient and provides a nonverbal way of interacting with clients, allowing them to connect with less burnout. They describe it as a person-centered, drug-free approach with a range of uses in drug abuse treatment, including: stress relief; relapse prevention; and symptom alleviation in methadone detoxification. Richard Elovich, Director of Substance Use Counseling and Education (SUCE), states that SUCE's HIV Services runs a successful acupuncture clinic.
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In addition to providing therapeutic benefits, the service opens the door to those who come for acupuncture but eventually seek out other assistance. •
Substance Abuse, Part II - Prevention & Beyond: A National Conference on HIV Infection and AIDS Among Racial and Ethnic Populations Summary: This videorecording presents the second part of a workshop on substance abuse, taped at a conference on HIV/AIDS among racial and ethnic populations. An intervention specialist from Miami, FL, opens the session with a description of her project on "cocaine babies". Under Florida law, babies testing positive for drugs at birth are removed from their mother; the mother must enter drug treatment and the babies are cared for by other relatives or foster care. However, many questions have arisen, such as what to do with other children in the family. The next speaker is from the Veteran's Administration (VA), and outlines the VA's drug and alcohol treatment programs. He relates how intravenous drug use has increased rates of HIV, with higher rates among veterans than in the general population. A physician with a methadone treatment center in Brooklyn, NY, addresses problems facing minority intravenous drug users (IVDUs). He claims that drug abuse is a multifactorial disease and should be treated with a comprehensive approach including counseling and treatment. The final speaker represents the Asian American Drug Use Program in Los Angeles, CA. He sees a waning public policy effort for fighting drug abuse. Outlining Asian and Pacific Islander mores, he reflects on the intense denial concerning drug abuse in those cultures.
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Choices: HIV Testing for Women and Children Contact: New York Department of Health, Corning Tower Rm 1084, Empire State Plz, Albany, NY, 12237, (518) 474-5370. Summary: This videorecording uses actresses to portray case studies of women who faced the decision of whether or not to take the test for Human immunodeficiency virus (HIV) antibodies. The actresses use the words of actual women who told their stories to the sponsoring agency as they discuss feelings of fear, anxiety, denial, and anger. While most have been tested, one woman tells how her fear has kept her from taking the test or having her infant son tested. Many of the infected women contracted the virus through IV-needle sharing, or through sex with a husband who abused drugs. They touch on topics of safer sexual conduct, pregnancy, counseling, and methadone treatment, and discuss difficulties in getting treatment for their children.
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “methadone” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on methadone: •
AIDS: Kids, Prostitutes and Drug Users Contact: National Public Radio, 2025 M St NW, Washington, DC, 20036, (202) 822-2000. Summary: This sound recording deals with children with Acquired immunodeficiency syndrome (AIDS), sex workers, and Intravenous drug users (IVDU's), in Newark, NJ.
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Female sex workers in Newark have one of the highest rates of infection with the Human immunodeficiency virus (HIV) in the United States. Several sex workers are interviewed, and their use of drugs and condoms is discussed. The lack of definitive research on the likelihood of a female sex worker transmitting HIV to a client is explained. IVDU's are also interviewed. The use of peer counselors to encourage them to seek and continue treatment, including methadone programs, is described. The children of IVDU's are frequently born addicted to drugs and/or infected with HIV. Children's Hospital in Newark has a special ward and a team of health professionals for treating these children. Various members of the staff are interviewed. They describe common childhood opportunistic infections and the devastating effects of HIV on normal development in many cases. Several vivid case studies are discussed, including the foster mother of three children with AIDS. The high rates of infection in Black and Hispanic children are also analyzed.
Bibliography: Multimedia on Methadone The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in methadone (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on methadone (for more information, follow the hyperlink indicated): •
Getting off heroin with methadone [videorecording]. Videorecording; [Toronto, Ont.]: Elan Productions, 1995
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Methadone [videorecording]: curse or cure? Source: [presented by] Filmakers Library, Inc; Year: 1994; Format: Videorecording; New York, N.Y.: Filmakers Library, [1994]
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Methadone [videorecording]: where we are Source: produced by Issembert Productions [and] NIDA; Year: 1993; Format: Videorecording; [Rockville, Md.]: National Institute on Drug Abuse, [1993]
Year:
1995;
Format:
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CHAPTER 8. PERIODICALS AND NEWS ON METHADONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover methadone.
News Services and Press Releases One of the simplest ways of tracking press releases on methadone is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “methadone” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to methadone. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “methadone” (or synonyms). The following was recently listed in this archive for methadone: •
Methadone enhances HIV infection of human immune cells Source: Reuters Industry Breifing Date: January 15, 2002
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Methadone maintenance at home may work for some addicts Source: Reuters Medical News Date: January 14, 2002
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Safe and effective IV fentanyl-to-methadone conversion ratio described Source: Reuters Medical News Date: October 19, 2001
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Lopinavir-ritonavir may cause opiate withdrawal in methadone-treated patients Source: Reuters Industry Breifing Date: September 24, 2003
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Effective methadone dose does not harm newborns Source: Reuters Health eLine Date: September 17, 2003
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Using methadone for pain may boost accidental death Source: Reuters Health eLine Date: July 01, 2003
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Methadone care for US heroin addicts found lacking Source: Reuters Health eLine Date: August 20, 2002
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Methadone therapy does not reduce HIV-related risk behaviors Source: Reuters Medical News Date: May 29, 2001
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Methadone stimulates HIV infection of immune cells Source: Reuters Health eLine Date: May 17, 2001
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Methadone stimulates in vitro infection in certain HIV strains Source: Reuters Medical News Date: May 16, 2001
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Liver transplant should not prevent methadone use Source: Reuters Health eLine Date: February 27, 2001
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OraSure screening assay for barbiturates, methadone approved Source: Reuters Industry Breifing Date: January 26, 2001
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New rules issued for methadone programs Source: Reuters Health eLine Date: January 17, 2001
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Roxane's Orlaam, Reckitt and Colman's Subutex may offer alternative to methadone Source: Reuters Industry Breifing Date: November 02, 2000
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Levomethadyl acetate and buprenorphine rival methadone in treating addiction Source: Reuters Medical News Date: November 01, 2000
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Methadone decreases the absorption rate of didanosine and stavudine Source: Reuters Medical News Date: September 25, 2000
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Longer methadone treatment best for heroin addicts Source: Reuters Health eLine Date: March 10, 2000
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Office-based methadone prescribing advocated for US; abbreviated therapy not effective Source: Reuters Medical News Date: March 08, 2000
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Heroin addicts benefit from better access to methadone Source: Reuters Health eLine Date: March 08, 2000
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Methadone eases recovery after prostate surgery Source: Reuters Medical News Date: October 15, 1999
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Methadone eases pain after prostate surgery Source: Reuters Health eLine Date: October 14, 1999
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High methadone dosage for drug users does not eliminate risk of HIV infection Source: Reuters Medical News Date: September 20, 1999
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Methadone equivalent shows promise for cocaine addiction Source: Reuters Medical News Date: August 26, 1999
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Site rotation, dexamethasone reduce local toxicity of subcutaneous methadone Source: Reuters Medical News Date: August 20, 1999
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HHS proposes accreditation of methadone programs Source: Reuters Medical News Date: July 23, 1999
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Nevirapine interacts with methadone and may induce opiate withdrawal Source: Reuters Medical News Date: June 03, 1999
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Higher methadone doses achieve better outcomes in opioid-dependent patients Source: Reuters Medical News Date: March 18, 1999
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High-dose methadone better than low Source: Reuters Health eLine Date: March 17, 1999
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Number of German methadone overdoses increasing Source: Reuters Medical News Date: March 08, 1999
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Enhanced standard methadone program comparable to more expensive program Source: Reuters Medical News Date: January 19, 1999
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NIH panel backs methadone treatment Source: Reuters Health eLine Date: December 08, 1998
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Call for greater use of methadone substitute Source: Reuters Health eLine Date: September 29, 1998
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Methadone treatment increases zidovudine levels in HIV-infected subjects Source: Reuters Medical News Date: August 20, 1998
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Methadone effective for some patients with severe refractory headache Source: Reuters Medical News Date: August 20, 1998
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NIH Panel Recommends Wider Use Of Methadone For Heroin Addicts Source: Reuters Medical News Date: November 20, 1997
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Feds Urge Wider Methadone Access Source: Reuters Health eLine Date: November 20, 1997
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Drug Czar Promotes Methadone Maintenance For Heroin Addicts Source: Reuters Medical News Date: October 06, 1997
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Methadone Useful In Refractory Chronic Daily Headache Source: Reuters Medical News Date: September 18, 1997 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “methadone” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.
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Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “methadone” (or synonyms). If you know the name of a company that is relevant to methadone, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “methadone” (or synonyms).
Academic Periodicals covering Methadone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to methadone. In addition to these sources, you can search for articles covering methadone that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for methadone. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with methadone. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to methadone: Levomethadyl •
Systemic - U.S. Brands: Orlaam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202766.html
Narcotic Analgesics for Pain Relief •
Systemic - U.S. Brands: Astramorph PF; Buprenex; Cotanal-65; Darvon; DarvonN; Demerol; Dilaudid; Dilaudid-5; Dilaudid-HP; Dolophine; Duramorph; Hydrostat IR; Kadian; Levo-Dromoran; M S Contin; Methadose; MS/L; MS/L Concentrate; MS/S; MSIR; Nubain; Numorphan; OMS Concentrate; http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202390.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “methadone” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “methadone” (or synonyms) into the “For these words:” box. The following is a sample result: •
HIV - Related Knowledge and Behaviors Among Clients in Methadone Maintenance Programs in Detroit Contact: Michigan Department of Public Health, HIV/AIDS Prevention and Intervention Section, PO Box 30195, Lansing, MI, 48909, (517) 335-8371. City of Detroit Department of Human Services, Gratiot Clinic, 3506 Gratiot, Detroit, MI, 48207, (313) 852-4846, http://www.ci.detroit.mi.us/humanservices/default.htm. Summary: This report describes a survey used to investigate knowledge about Human immunodeficiency virus (HIV) and Acquired immunodeficiency syndrome (AIDS) among Intravenous drug users (IVDU's) at a methadone maintenance program. The findings indicate a lower awareness of HIV transmission through sexual intercourse and IV-needle sharing than among the general population and a high incidence of multiplerisk behaviors. The report calls for continuing efforts to educate IVDU's about HIV transmission and to promote safer sexual conduct, particularly condom use.
•
A Comparative Analysis of Two Methods of AIDS Education in a Population of Methadone and Non-Methadone Taking Substance Abusers: Preliminary Report Contact: Greenwich House, 27 Barrow St, New York, NY, 10014, (212) 242-4140. Summary: This report of a study, using a longitudinal, quasi-experimental pre- and post-test design, determines the comparative effectiveness of facilitative (participatory) and didactic (lecture) methods of delivering an AIDS education and HIV prevention program to methadone taking and non-methadone taking injecting drug users (IDUs). Both education programs include role playing, videos, and published materials. The study also yielded baseline information about knowledge and opinions on AIDS, and sexual and drug-taking practices among this population. The measurements were taken immediately preceding education intervention, immediately following educational intervention, and three months following educational intervention. The data were analyzed by nine independent variables: type of educational intervention, methadone use or non-use, sex, age, race, sexual orientation, level of education, marital status, and household income. Knowledge, opinion, and safer sexual and drug-taking practices were the dependent variables. An AIDS knowledge scale encompassed three subscales:
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general AIDS knowledge, sex-related AIDS knowledge, and drug-related AIDS knowledge. The findings indicate that overall knowledge levels were increased as a result of either type of AIDS educational intervention; the intervention had an increasing impact as the general educational level increased. However, the facilitative approach produced a higher increase in all AIDS knowledge scales, for reasons not yet determined. Despite an original hypothesis, methadone users appeared to experience a slightly higher increase in the total AIDS knowledge scale. •
State Methadone Treatment Guidelines Contact: US Department of Health and Human Services, Public Health Service, Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment, 5600 Fisher Lane, Rockwall 2, Rockville, MD, 20852, (301) 443-7730. Summary: This treatment protocol on state methadone treatment guidelines serves as a blueprint for state policy officials and methadone maintenance treatment providers. The protocol presents the effective, state-of-the-art therapeutic techniques for methadone maintenance treatment. The first chapter presents an overview of current treatment realities and future treatment trends. Chapter two reviews the social transformation that occurred within the United States during the past century that placed disparate groups at risk for dependence on narcotics. Chapter 3 reviews some of the major issues facing treatment providers in methadone maintenance. Chapter four focuses on admission policies and procedures. Chapter 5 explores dose determination and the basic principles of managing pain and addresses the common misconceptions regarding approaches to adequate pain management for methadone patients. Chapter 6 examines urine screening programs. Chapter 7 discusses the general principles regarding clinical indications for take-home medication and for monitoring patients who receive take-home medication. Chapter 8 addresses multiple substance use within the context of methadone maintenance treatment. Chapter 9 discusses the issues relevant to methadone maintenance during pregnancy. Chapter 10 highlights HIV and other infectious diseases. Chapter 11 addresses patient retention and treatment duration. The 12th chapter contains a portrait of useful elements of community cooperation, providing a broad perspective on developing successful community education and relations practices. The protocol concludes with an epilogue that provides a historical overview of the development of methadone as a successful treatment strategy.
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “methadone” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category.
13 14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 7918 179 95 600 40 8832
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “methadone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
15
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
16
The HSTAT URL is http://hstat.nlm.nih.gov/.
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Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 18 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 19
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on methadone can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to methadone. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to methadone. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “methadone”:
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Other guides Amphetamine Abuse http://www.nlm.nih.gov/medlineplus/amphetamineabuse.html Club Drugs http://www.nlm.nih.gov/medlineplus/clubdrugs.html Prescription Drug Abuse http://www.nlm.nih.gov/medlineplus/prescriptiondrugabuse.html
Within the health topic page dedicated to methadone, the following was listed: •
General/Overviews Drug Abuse: How to Break the Habit http://familydoctor.org/healthfacts/357/ http://familydoctor.org/healthfacts/357/ Drug Addiction Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00183
•
Treatment Buprenorphine Approval Expands Options for Addiction Treatment Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N4/Buprenorphine.html Office-Based Therapy for Opiate Addiction Successful: Option Can Increase Number of Patients Seeking Treatment Source: National Institute on Drug Abuse http://www.nih.gov/news/pr/sep2003/nida-03.htm Principles of Drug Addiction Treatment: A Research-Based Guide Source: National Institute on Drug Abuse http://www.nida.nih.gov/PODAT/PODATindex.html Subutex and Suboxone Approved to Treat Opiate Dependence Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01165.html Treatment Medications Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/treatmed.html Treatment Methods Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/treatmeth.html Types of Treatment (Drug Addiction) Source: Office of National Drug Control Policy http://www.whitehousedrugpolicy.gov/treat/treatment.html
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Specific Conditions/Aspects Alcohol or Drug Abuse Recovery: Your Doctor Can Help Source: American Academy of Family Physicians http://familydoctor.org/handouts/152.html Hallucinogens and Dissociative Drugs: Including LSD, PCP, Ketamine, Dexteromethorpban Source: National Institute on Drug Abuse http://www.nida.nih.gov/ResearchReports/hallucinogens/hallucinogens.html Inhalant Abuse Source: National Institute on Drug Abuse http://www.nida.nih.gov/ResearchReports/Inhalants/Inhalants.html Inhalants Source: National Institute on Drug Abuse http://www.nida.nih.gov/Infofax/inhalants.html New Insights Into Relapse Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N3/DirRepVol17N3.html Oops: How Casual Drug Use Leads to Addiction Source: National Institute on Drug Abuse http://www.nida.nih.gov/Published_Articles/Oops.html PCP (Phencyclidine) Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/pcp.html Prescription Drugs: Abuse and Addiction Source: National Institute on Drug Abuse http://www.drugabuse.gov/ResearchReports/Prescription/prescription8.html Principles of HIV Prevention in Drug-Using Populations: Frequently Asked Questions: Effectiveness of Strategies Source: National Institute on Drug Abuse http://www.nida.nih.gov/POHP/FAQ_2.html Principles of HIV Prevention in Drug-Using Populations: Frequently Asked Questions: Prevention Strategies Source: National Institute on Drug Abuse http://www.nida.nih.gov/POHP/FAQ_1.html Substance Abuse Issues in Cancer (PDQ) Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/supportivecare/substanceabuse/patient / Viral Hepatitis and Injection Drug Users Source: National Center for HIV, STD, and TB Prevention http://www.cdc.gov/idu/hepatitis/viral_hep_drug_use.htm
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Children Common Inhalants Source: American Academy of Pediatrics http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZDARS2B7C &sub_cat=23 Preventing Substance Abuse Source: American Academy of Pediatrics http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZXK31WR7C &sub_cat=466 Sara's Quest Challenge Source: National Institute on Drug Abuse http://www.sarasquest.org/Quest/SQuesttext.html Talking to Your Child About Drugs Source: Nemours Foundation http://kidshealth.org/parent/emotions/behavior/talk_about_drugs.html
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From the National Institutes of Health Commonly Abused Drugs Source: National Institute on Drug Abuse http://www.nida.nih.gov/DrugsofAbuse.html Understanding Drug Abuse and Addiction Source: National Institute on Drug Abuse http://www.nida.nih.gov/Infofax/understand.html
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Journals/Newsletters NIDA Notes Index Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_Notes/NNindex.html
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Latest News Anti-drug Ads Get Teens' Attention Source: 09/24/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14081 .html More News on Drug Abuse http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/alphanews_d.html#D rugAbuse Most Substance Abuse Programs Ignore the Elderly Source: 10/17/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14340 .html Office-Based Therapy for Opiate Addiction Successful: Option Can Increase Number of Patients Seeking Treatment Source: 09/03/2003, National Institute on Drug Abuse http://www.nih.gov/news/pr/sep2003/nida-03.htm
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Severe Childhood ADHD May Predict Alcohol, Substance Use Problems in Teen Years Source: 08/17/2003, National Institute on Alcohol Abuse and Alcoholism http://www.nih.gov/news/pr/aug2003/niaaa-17.htm U.N. Sounds Alarm Over Brain-Killing Drugs Source: 09/23/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14059 .html •
Law and Policy Global Issues: Narcotics Source: United States Information Agency http://usinfo.state.gov/gi/global_issues/narcotics.html
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Men Substance Abuse Facilities Offering Special Programs or Services for Women Source: Substance Abuse and Mental Health Services Administration http://www.samhsa.gov/oas/2k2/FemServices/FemServices.htm Treatment Methods for Women Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/treatwomen.html
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Organizations American Council for Drug Education http://www.acde.org/ Drug Enforcement Administration http://www.usdoj.gov/dea/ Higher Education Center for Alcohol and Other Drug Prevention Source: Dept. of Education http://www.edc.org/hec/ National Clearinghouse for Alcohol and Drug Information Source: Dept. of Health and Human Services, Substance Abuse and Mental Health Services Administration http://www.health.org/ National Institute on Drug Abuse http://www.nida.nih.gov/ Office of National Drug Control Policy http://www.whitehousedrugpolicy.gov/ Partnership for a Drug-Free America http://drugfreeamerica.com/Home/Default.asp?ws=PDFA&vol=1&grp=Home Substance Abuse and Mental Health Services Administration http://www.samhsa.gov/
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Prevention/Screening Preventing Drug Use Among Children and Adolescents: A Research-Based Guide Source: National Institute on Drug Abuse http://www.nida.nih.gov/Prevention/Prevopen.html
•
Research Adolescent Treatment Programs Reduce Drug Abuse, Produce Improvements Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_Notes/NNVol17N1/Adolescent.html
Other
Childhood Sex Abuse Increases Risk for Drug Dependence in Adult Women Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_Notes/NNVol17N1/Childhood.html Chronic Solvent Abusers Have More Brain Abnormalities and Cognitive Impairments Than Cocaine Abusers Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N4/Chronic.html Depression, PTSD, Substance Abuse Increase in Wake of September 11 Attacks Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N4/Depression.html Family-Based Treatment Programs Can Reduce Adolescent Drug Abuse Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N4/Family.html Few Middle Schools Use Proven Prevention Programs Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N6/MiddleSchool.html Grouping High-Risk Youths for Prevention May Harm More Than Help Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N5/Grouping.html NIDA Addiction Research News http://www.nih.gov/news/pr/mar2003/nida-06.pdf Severe Childhood ADHD May Predict Alcohol, Substance Use Problems in Teen Years Source: National Institute on Alcohol Abuse and Alcoholism http://www.nih.gov/news/pr/aug2003/niaaa-17.htm Shortened Family Prevention Programs Yield Long-Lasting Reductions in Adolescent Drug Abuse Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_Notes/NNVol17N2/Shortened.html Youths' Opportunities To Experiment Influence Later Use of Illegal Drugs Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N5/Youths.html
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•
Statistics 2002 Monitoring the Future Survey Shows Decrease in Use of Marijuana, Club Drugs, Cigarettes and Tobacco Source: National Institute on Drug Abuse http://www.nih.gov/news/pr/dec2002/nida-16.htm 22 Million in U.S. Suffer from Substance Dependence or Abuse Source: Dept. of Health and Human Services http://www.hhs.gov/news/press/2003pres/20030905.html FASTATS: Illegal Drug Use Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/druguse.htm Gender and Ethnic Patterns in Drug Use Among High School Seniors Source: National Institute on Drug Abuse http://www.drugabuse.gov/NIDA_notes/NNVol18N2/tearoff.html High School and Youth Trends Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/HSYouthtrends.html Highlights - 2001 National Household Survey on Drug Abuse Source: Substance Abuse and Mental Health Services Administration http://www.samhsa.gov/oas/nhsda/2k1nhsda/vol1/highlights.htm Inhalant Abuse Among Young People Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N4/tearoff.html Teen Drug Use Declined in 2002, Report Shows Source: National Institute on Drug Abuse http://www.nida.nih.gov/NIDA_notes/NNVol17N5/Teen.html Treatment Admissions for Injection Drug Abuse Source: Substance Abuse and Mental Health Services Administration http://www.samhsa.gov/oas/2k2/ivdrugTX/ivdrugTX.htm
•
Teenagers Dealing with Addiction Source: Nemours Foundation http://kidshealth.org/teen/your_mind/problems/addictions.html Don't Harm Yourself Source: National Institute on Drug Abuse http://www.nida.nih.gov/dontharm/page1/dontharm1.html Dual Diagnosis in Adolescence Source: National Alliance for the Mentally Ill http://www.nami.org/Content/ContentGroups/Helpline1/Dual_Diagnosis_in_A dolescence.htm Family Guide to Keeping Youth Mentally Healthy and Drug Free Source: Substance Abuse and Mental Health Services Administration http://family.samhsa.gov/
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Get It Straight! Here's How the Pages Shake Down Source: Drug Enforcement Administration http://www.usdoj.gov/dea/pubs/straight/toc.htm Helping Kids Keep Themselves Out of Hot Water Source: Center for Mental Health Services http://www.family.samhsa.gov/teach/pressure/summer.aspx NIDA for Teens Source: National Institute on Drug Abuse http://www.teens.drugabuse.gov/ Substance Use and Sexual Health among Teens and Young Adults in the U.S. http://www.kff.org/content/2002/3213/CASAFactSheet.pdf •
Women Substance Abuse Facilities Offering Special Programs or Services for Women Source: Substance Abuse and Mental Health Services Administration http://www.samhsa.gov/oas/2k2/FemServices/FemServices.htm Treatment Methods for Women Source: National Institute on Drug Abuse http://www.nida.nih.gov/infofax/treatwomen.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on methadone. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Prevention and Treatment : Methadone Contact: Canadian Public Health Association, Canadian HIV/AIDS Clearinghouse, 4001565 Carling Ave Ste 400, Ottawa, (613) 725-3434, http://www.cpha.ca. Summary: This fact sheet discusses the need for methadone maintenance treatment (MMT) to be made available to incarcerated persons who are injection drug users (IDUs) in an effort to prevent the transmission of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and the hepatitis C virus (HCV) in Canadian correctional facilities. The fact sheet identifies countries in which correctional systems offer prisoners MMT. In Canada, MMT has been made available
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only recently as a result of legal action. In Canada, federal and provincial prison systems have adopted a policy of making MMT available only to those persons who had received MMT before entering the prison system; there has been no provision made for opiate-dependent persons who had not been on MMT prior to becoming incarcerated. The fact sheet recommends that MMT should be available to opiate-dependent people regardless of whether they are outside or inside prison, and, in addition, opiatedependent prisoners should have other treatment options. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to methadone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Associations and Methadone The following is a list of associations that provide information on and resources relating to methadone: •
American Association for the Treatment of Opioid Dependence, Inc Telephone: (212) 566-5555 Fax: (212) 349-2944 Email:
[email protected] Web Site: www.aatod.org
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Background: The American Association for the Treatment of Opioid Dependence, Inc. was founded in 1984 to promote the growth and development of opioid treatment services. The Association currently represents 20 states and the District of Columbia, providing treatment to individuals in approximately 700 programs. Committed to enhancing the quality of patient care, the American Association for the Treatment of Opioid Dependence, in conjunction with the American Society of Addiction Medicine, developed clinical guidelines to assist individual practitioners and policy makers in the development of effective opioid treatment services. In addition, the Association focuses on federal, state, and program specific treatment policies; advocates on behalf of affected individuals and their families; engages in professional and public education; and promotes the coordination of and communication among opioid treatment programs. The Association also convenes a National Conference every 18 months for researchers, treatment personnel, and policy makers. The Association also provides a variety of materials including fact sheets and brochures, and maintains a website with information about opioid treatment for patients and practitioners, national advisories and policy statements, news from the states, and Conference/Symposium registration materials.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to methadone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with methadone. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about methadone. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “methadone” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given
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the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “methadone”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “methadone” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “methadone” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 313
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 315
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
316 Methadone
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on methadone: •
Basic Guidelines for Methadone Methadone overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002679.htm
•
Signs & Symptoms for Methadone Bluish colored fingernails and lips Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Constipation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003125.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm
318 Methadone
Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Muscle spasticity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weak pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003078.htm •
Diagnostics and Tests for Methadone Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm
•
Background Topics for Methadone Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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METHADONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abacavir: A nucleoside analog reverse transcriptase inhibitor (NARTIs) developed by Glaxo Wellcome. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acclimation: Adaptation of animals or plants to new climate. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH]
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Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alcohol Withdrawal Delirium: Temporary state of mental confusion because of active uncontrolled imagination and faulty judgment. Among the causes are intoxications. [NIH] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]
Alfentanil: A short-acting opioid anesthetic and analgesic derivative of fentanyl. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU]
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Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Ambulant: Walking or able to walk. [EU] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amniotic Band Syndrome: A disorder present in the newborn infant in which constriction rings or bands, causing soft tissue depressions, encircle digits, extremities, or limbs and sometimes the neck, thorax, or abdomen. They may be associated with intrauterine amputations. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH]
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Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic,
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or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat
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schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Art Therapy: The use of art as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH]
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Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-aminoacids is obtained by the hydrolysis of proteins. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance
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whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomedical Engineering: Application of principles and practices of engineering science to biomedical research and health care. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Banks: Centers for collecting, characterizing, and storing human blood. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH]
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Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bombesin: A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU]
Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and
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kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [NIH] Cadaver: A dead body, usually a human body. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogenicity: The ability to cause cancer. [NIH] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both
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genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Degranulation: The process of losing secretory granules (secretory vesicles). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by exocytosis. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Depressants: A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents). [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary
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process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Child Development: The continuous sequential physiological and psychological maturing of the child from birth up to but not including adolescence. It includes healthy responses to situations, but does not include growth in stature or size (= growth). [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is
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important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic prostatitis: Inflammation of the prostate gland, developing slowly and lasting a long time. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Competence: The capability to perform acceptably those duties directly related to patient care. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning:
The production of a number of genetically identical individuals; in genetic
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engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] CNS: Central nervous system. The brain and spinal cord. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU]
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Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Community Health Services: Diagnostic, therapeutic and preventive health services provided for individuals in the community. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques
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for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried
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by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [NIH] Cost-Benefit Analysis: A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. Cost effectiveness compares alternative ways to achieve a specific set of results. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Criterion: A standard by which something may be judged. [EU] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as
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cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, ... New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial
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relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]
Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Designer Drugs: Drugs designed and synthesized, often for illegal street use, by modification of existing drug structures (e.g., amphetamines). Of special interest are MPTP (a reverse ester of meperidine), MDA (3,4-methylenedioxyamphetamine), and MDMA (3,4methylenedioxymethamphetamine). Many drugs act on the aminergic system, the physiologically active biogenic amines. [NIH] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] DEXA: A method (dual energy X-ray absortiometry) used to estimate total body fat and percent of body fat. Potential disadvantages include whole body radiation and the long time required for scanning while the subject lies on a hard table. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dexmedetomidine: A selective inhibitor of receptors, adrenergic alpha-2 that has analgesic and sedative properties. Medetomidine is the other racemic form. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of
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attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. [NIH] Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to didanosine (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention
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of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disopyramide: Alpha-(2-(Bis(l-methylethyl)amino)ethyl)-alpha-phenyl-2-pyridine acetamide. A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy;
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superior in the anatomy of quadrupeds. [EU] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ego: The conscious portion of the personality structure which serves to mediate between the demands of the primitive instinctual drives, (the id), of internalized parental and social prohibitions or the conscience, (the superego), and of reality. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures
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that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent
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naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enhancers: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
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Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Etorphine: A narcotic analgesic morphinan used as a sedative in veterinary practice. [NIH] Euphoria: An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Father-Child Relations: Interaction between the father and the child. [NIH] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue
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development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Fractures: Fractures of the femur. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Flunitrazepam: Benzodiazepine with pharmacologic actions similar to those of diazepam. The United States Government has banned the importation of this drug. Steps are being taken to reclassify this substance as a Schedule 1 drug with no accepted medical use. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH]
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Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]
Forearm: The part between the elbow and the wrist. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]
Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-Glutamyltransferase: An enzyme that catalyzes reversibly the transfer of a glutamyl group from a glutamyl-peptide and an amino acid to a peptide and a glutamylamino acid. EC 2.3.2.2. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
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[NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH]
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Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanfacine: A centrally acting antihypertensive agent. The drug lowers both systolic and diastolic blood pressure by activating the central nervous system alpha-2 adrenoreceptors, which results in reduced sympathetic outflow leading to reduced vascular tone. Its adverse reactions include dry mouth, sedation, and constipation. [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Halfway Houses: Specialized residences for persons who do not require full hospitalization, and are not well enough to function completely within the community without professional supervision, protection and support. [NIH] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations.. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH]
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Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatoma: A liver tumor. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heroin Dependence: Strong dependence, both physiological and emotional, upon heroin. [NIH]
Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] HIV: Human immunodeficiency virus. Species of lentivirus, subgenus primate lentiviruses,
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formerly designated T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). It is acknowledged to be the agent responsible for the acute infectious manifestations, neurologic disorders, and immunologic abnormalities linked to the acquired immunodeficiency syndrome. [NIH] HIV Protease: Enzyme of the human immunodeficiency virus that is required for posttranslational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. EC 3.4.23.- [NIH] HIV Protease Inhibitors: Inhibitors of HIV protease, an enzyme required for production of proteins needed for viral assembly. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydromorphone: An opioid analgesic made from morphine and used mainly as an analgesic. It has a shorter duration of action than morphine. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxytryptophol: 5-Hydroxy-indole-3-ethanol. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased
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tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypnotherapy: Sleeping-cure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibogaine: One of several indole alkaloids extracted from Tabernanthe iboga, Baill. It has a complex pharmacological profile and interacts with multiple systems of neurotransmission. Ibogaine has psychoactive properties and appears to modulate tolerance to opiates. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Illusions: The misinterpretation of a real external, sensory experience. [NIH] Imagination: A new pattern of perceptual or ideational material derived from past experience. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: (antigens). [NIH]
The activity of the immune system against foreign substances
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
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Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]
Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH]
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Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Instillation: . [EU] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intercostal: Situated between the ribs. [EU] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interindividual: Occurring between two or more individuals. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH]
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Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH]
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Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]
Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lethal: Deadly, fatal. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: circulation. [NIH]
Services offered to the library user. They include reference and
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery.
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Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobule: A small lobe or subdivision of a lobe. [NIH] Local Government: Smallest political subdivisions within a country at which general governmental functions are carried-out. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH]
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Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysergic acid: A compound close in chemical structure to LSD-25 but without hallucinogenic effects; one of the direct chemical predecessors of LSD-25. Sometimes LSD-25 is erroneously called by this name. [NIH] Lysergic Acid Diethylamide: Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Mazindol: Tricyclic anorexigenic agent unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]
Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: illnesses. [NIH]
Recording of pertinent information concerning patient's illness or
MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH]
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Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Health Services: Organized services to provide mental health care. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions
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which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]
Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA,
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can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis:
A general and nonspecific reversible depression of neuronal excitability,
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produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle Sharing: Usage of a single needle among two or more people for injecting drugs. Needle sharing is a high-risk behavior for contracting infectious disease. [NIH] Needle-Exchange Programs: Organized services for exchange of sterile needles and syringes used for injections as a potential means of reducing the transmission of infectious diseases. [NIH] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Abstinence Syndrome: Fetal and neonatal addiction and withdrawal as a result of the mother's dependence on drugs during pregnancy. Withdrawal or abstinence symptoms develop shortly after birth. Symptoms exhibited are loud, high-pitched crying, sweating, yawning and gastrointestinal disturbances. [NIH] Neonatal period: The first 4 weeks after birth. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system).
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[EU]
Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]
Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide
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activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonmalignant: Not cancerous. [NIH] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nursing Staff: Personnel who provide nursing service to patients in an organized facility, institution, or agency. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or
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images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ownership: The legal relation between an entity (individual, group, corporation, or-profit, secular, government) and an object. The object may be corporeal, such as equipment, or completely a creature of law, such as a patent; it may be movable, such as an animal, or immovable, such as a building. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH]
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Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Pain Threshold: experienced. [NIH]
Amount of stimulation required before the sensation of pain is
Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Parent-Child Relations: The interactions between parent and child. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a
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registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU]
Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity
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by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenazopyridine: A local anesthetic that has been used in urinary tract disorders. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity. [NIH]
Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physicochemical: Pertaining to physics and chemistry. [EU] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental tissue: The tissue intervening between fetal blood and maternal blood in the placenta; it acts as a selective membrane regulating the passage of substances from the maternal to the fetal blood. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU]
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Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polyproteins: Proteins which are synthesized as a single polymer and then cleaved into several distinct proteins. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH]
Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH]
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Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Health Services: Services designed for promotion of health and prevention of disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones,
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in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU]
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Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychophysics: The science dealing with the correlation of the physical characteristics of a stimulus, e.g., frequency or intensity, with the response to the stimulus, in order to assess the psychologic factors involved in the relationship. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Assistance: Financial assistance to impoverished persons for the essentials of living through federal, state or local government programs. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Housing: Housing subsidized by tax funds, usually intended for low income persons or families. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse:
The rhythmical expansion and contraction of an artery produced by waves of
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pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH]
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Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Adrenergic: Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference point: The midpoint of a line connecting the centers of the two end faces of the acoustic test fixture. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Refractory cancer: Cancer that has not responded to treatment. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [EU] Reinforcement Schedule: A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication
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and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory Muscles: These include the muscles of the diaphragm and the intercostal muscles. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Rifabutin: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk-Taking: Undertaking a task involving a challenge for achievement or a desirable goal in which there is a lack of certainty or a fear of failure. It may also include the exhibiting of certain behaviors whose outcomes may present a risk to the individual or to those associated with him or her. [NIH] Ritalin: Drug used to treat hyperactive children. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Role Playing: The adopting or performing the role of another significant individual in order to gain insight into the behavior of that person. [NIH] Saccharin: Flavoring agent and non-nutritive sweetener. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH]
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Salivary glands: Glands in the mouth that produce saliva. [NIH] Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Semen:
The thick, yellowish-white, viscid fluid secretion of male reproductive organs
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discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skilled Nursing Facilities: Extended care facilities which provide skilled nursing care or rehabilitation services for inpatients on a daily basis. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH]
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Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and
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types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirochete: Lyme disease. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [NIH] Steady state: Dynamic equilibrium. [EU] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]
Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU]
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Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Supraspinal: Above the spinal column or any spine. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of
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disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU]
Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis
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sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Therapeutic Community: Psychotherapeutic technique which emphasizes socioenvironmental and interpersonal influences in the resocialization and rehabilitation of the patient. The setting is usually a hospital unit or ward in which professional and nonprofessional staff interact with the patients. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH]
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Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tractus: A part of some structure, usually that part along which something passes. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy,
382 Methadone
effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trimeprazine: A phenothiazine derivative that is used as an antipruritic. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urine Testing: Checking urine to see if it contains glucose (sugar) and ketones. Special strips of paper or tablets (called reagents) are put into a small amount of urine or urine plus water. Changes in the color of the strip show the amount of glucose or ketones in the urine. Urine testing is the only way to check for the presence of ketones, a sign of serious illness. However, urine testing is less desirable then blood testing for monitoring the level of glucose in the body. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond
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to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH]
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Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vital Statistics: Used for general articles concerning statistics of births, deaths, marriages, etc. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Waiting Lists: Prospective patient listings for appointments. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yawning: An involuntary deep inspiration with the mouth open, often accompanied by the act of stretching. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-
Dictionary 385
terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
387
INDEX A Abacavir, 181, 319 Abdomen, 319, 321, 327, 352, 355, 365, 377, 380 Aberrant, 319, 332 Acceptor, 319, 363, 381 Acclimation, 43, 319 Acetylcholine, 319, 331, 361 Acoustic, 252, 319, 372 Acute renal, 213, 319 Adaptation, 51, 206, 258, 319, 330, 359, 367 Adenocarcinoma, 319, 348 Adenosine, 319, 366 Adjunctive Therapy, 319, 324 Adjustment, 65, 85, 319 Adjuvant, 20, 22, 60, 136, 319, 345 Adolescence, 305, 319, 330 Adrenal Cortex, 319, 335, 343, 368 Adrenal Medulla, 320, 329, 342, 362 Adrenergic, 19, 84, 320, 322, 324, 339, 342, 372, 378, 384 Adverse Effect, 3, 195, 243, 320, 332, 340, 375 Afferent, 33, 320 Affinity, 69, 320, 332, 337, 338, 372, 376 Agoraphobia, 320, 350, 364 Akathisia, 320, 324 Albumin, 320, 366 Alcohol Withdrawal Delirium, 131, 320 Aldehyde Dehydrogenase, 320, 339 Alfentanil, 73, 320 Algorithms, 67, 320, 326 Alimentary, 320, 364 Alkaline, 256, 321, 328 Alkaloid, 49, 51, 321, 327, 332, 359, 361, 364, 384 Allergen, 321, 337 Alternative medicine, 284, 321 Amantadine, 49, 120, 185, 321, 357 Ambulant, 126, 321 Ameliorated, 76, 321 Ameliorating, 3, 20, 321 Amenorrhea, 321, 327 Amino acid, 68, 321, 323, 324, 325, 338, 339, 345, 346, 358, 365, 368, 369, 375, 378, 381, 382 Amino Acid Sequence, 321, 323, 368 Ammonia, 321, 378, 382
Amnestic, 18, 321, 345, 358 Amniotic Band Syndrome, 202, 321 Amniotic Fluid, 321, 356 Amphetamine, 18, 39, 217, 219, 300, 321, 337, 356 Anaesthesia, 134, 154, 182, 194, 214, 221, 233, 236, 322, 351 Anal, 47, 77, 322, 355 Analog, 319, 322, 338, 344, 353, 374, 377 Analogous, 69, 94, 322, 381 Anaphylatoxins, 322, 333 Anatomical, 22, 51, 79, 322, 325, 330, 351 Anemia, 322, 385 Anesthesia, 67, 94, 134, 233, 243, 322, 353, 358 Anesthetics, 322, 325, 329, 342 Angina, 322, 353 Angina Pectoris, 322, 353 Animal model, 31, 50, 92, 100, 101, 322 Antagonism, 12, 18, 80, 322, 332, 356 Anti-Anxiety Agents, 322, 368, 370, 381 Antibacterial, 322, 353, 363, 377 Antibiotic, 322, 327, 365, 368, 373, 377 Antibiotic Prophylaxis, 322, 368 Antibodies, 25, 59, 170, 215, 278, 323, 347, 351, 355, 366, 375 Antibody, 25, 46, 135, 208, 272, 320, 323, 333, 347, 349, 350, 351, 356, 371, 376 Anticholinergic, 323, 339 Anticoagulant, 323, 369 Anticonvulsant, 60, 323, 355, 383 Antidepressant, 13, 62, 68, 97, 323, 328, 344, 350, 383 Antidepressive Agents, 323, 370 Antiemetic, 323, 324, 330 Antifungal, 323, 344, 353 Antigen, 320, 323, 333, 349, 350, 351, 356, 371 Antigen-Antibody Complex, 323, 333 Antihypertensive, 323, 347 Anti-inflammatory, 323, 325, 337, 338, 346 Anti-Inflammatory Agents, 323, 325 Antimetabolite, 323, 344, 373 Antipruritic, 323, 382 Antipsychotic, 24, 323, 330, 332, 360, 381 Antipyretic, 324, 338 Antispasmodic, 324, 363 Antitussive, 324, 338, 363
388 Methadone
Antiviral, 96, 321, 324, 352, 360, 373 Anus, 322, 324, 327, 333 Anxiety, 11, 237, 250, 256, 278, 320, 322, 324, 345, 350, 355, 362, 364 Anxiolytic, 324, 328, 358 Aperture, 324, 371 Aphasia, 321, 324 Apoptosis, 15, 148, 324 Applicability, 7, 93, 277, 324 Aqueous, 324, 325, 336, 341 Arginine, 322, 324, 361 Aromatic, 94, 324 Arrhythmia, 324, 383 Art Therapy, 249, 324 Arterial, 48, 249, 324, 349, 369, 379 Arteries, 324, 327, 334, 358 Arterioles, 324, 327, 328 Artery, 324, 325, 335, 338, 370 Aseptic, 19, 325, 363 Aspartate, 35, 60, 69, 115, 325, 338, 353, 366 Aspartic, 325, 341, 349 Aspirin, 196, 325 Assay, 56, 76, 105, 141, 236, 282, 325, 350, 371 Atmospheric Pressure, 176, 325, 349 Atrium, 325, 383 Attenuation, 20, 35, 185, 248, 325 Atypical, 24, 325, 332 Auricular, 6, 325 Autonomic, 81, 319, 324, 325, 362, 365 Autoradiography, 51, 52, 325 Axons, 325, 352 B Baclofen, 5, 50, 325 Bacteria, 322, 323, 325, 344, 346, 347, 358, 363, 373, 375, 377, 381, 383 Bacterial Infections, 325, 329, 347, 373 Bacterial Physiology, 319, 325 Bactericidal, 325, 343 Bacteriuria, 325, 382 Barbiturates, 215, 282, 325, 374 Basal Ganglia, 40, 324, 325, 331, 362 Base, 14, 67, 75, 325, 336, 337, 353, 379 Basophils, 326, 329, 346, 354 Behavior Therapy, 47, 87, 101, 109, 273, 326 Benign, 326, 347 Benzene, 326 Benzodiazepines, 7, 11, 123, 156, 210, 215, 225, 232, 271, 326, 328 Bile, 326, 345, 355, 356, 377
Bile Pigments, 326, 356 Binding Sites, 111, 124, 190, 326 Bioavailability, 61, 142, 210, 326, 351 Biochemical, 52, 323, 326, 344, 354, 365, 375 Biological response modifier, 326, 352 Biomedical Engineering, 71, 326 Biopsy, 67, 326, 365 Biotechnology, 111, 112, 274, 284, 293, 326 Bladder, 67, 326, 333, 335, 353, 354, 369, 382 Blastocyst, 326, 334, 366 Blood Banks, 272, 326 Blood Coagulation, 326, 327, 328, 380 Blood Glucose, 92, 327, 348 Blood Platelets, 327, 375 Blood pressure, 318, 323, 327, 329, 330, 349, 350, 359, 376 Blood vessel, 327, 328, 329, 330, 331, 334, 342, 343, 355, 365, 376, 377, 380, 383 Body Composition, 53, 327 Body Fluids, 327, 376 Bombesin, 15, 148, 327 Bone Marrow, 326, 327, 350, 355, 359, 385 Bone scan, 327, 374 Bowel, 230, 322, 327, 338, 352, 354, 377 Bowel Movement, 327, 338, 377 Bradykinin, 327, 361, 366 Brain Stem, 40, 327, 330 Branch, 270, 315, 327, 361, 364, 370, 376, 379, 380 Breakdown, 327, 338, 345 Broad-spectrum, 327, 363, 373 Bromocriptine, 49, 125, 327 Bupivacaine, 154, 327 Bupropion, 49, 108, 127, 328 Buspirone, 23, 42, 328 Butorphanol, 68, 77, 328 C Cadaver, 142, 328 Calcium, 21, 77, 328, 333, 353, 364, 383 Calcium channel blocker, 328, 383 Candidiasis, 262, 328, 344 Candidosis, 328 Cannabidiol, 18, 328 Cannabinoids, 18, 215, 328 Cannabinol, 328 Cannabis, 120, 127, 185, 328, 379 Capillary, 105, 129, 140, 150, 215, 219, 327, 328, 383 Carbon Dioxide, 328, 337, 350, 366, 373 Carcinogenesis, 15, 328
Index 389
Carcinogenic, 326, 328, 352, 377 Carcinogenicity, 328, 366 Carcinogens, 328, 384 Carcinoma, 328, 329 Cardia, 163, 329 Cardiac, 19, 225, 329, 339, 341, 342, 353, 358, 359, 377 Cardiorespiratory, 329, 358 Cardiovascular, 8, 32, 68, 273, 321, 329, 375, 380 Cardiovascular disease, 8, 329 Carrier Proteins, 329, 366, 371 Case report, 179, 202, 251, 329, 331 Case series, 329, 331 Catecholamine, 323, 329, 339, 366 Catheter, 19, 329, 354 Causal, 38, 256, 329 Cell Death, 324, 329 Cell Degranulation, 20, 329 Cell Size, 329, 344 Central Nervous System Depressants, 42, 329 Central Nervous System Infections, 329, 347 Centrifugation, 330, 358 Cerebellum, 330, 335, 345, 367, 372 Cerebral, 48, 76, 78, 128, 248, 253, 325, 327, 330, 334, 336, 342, 343, 345, 364, 370, 379 Cerebral hemispheres, 325, 327, 330, 379 Cerebrospinal, 19, 207, 330 Cerebrospinal fluid, 19, 207, 330 Cerebrovascular, 40, 185, 329, 330 Cerebrum, 330, 335, 379 Chemical Warfare, 330, 336 Chemical Warfare Agents, 330, 336 Chemoreceptor, 324, 330 Chemotactic Factors, 330, 333 Chemotherapeutic agent, 330, 338 Chemotherapy, 159, 250, 330 Child Development, 77, 330 Chin, 127, 240, 330, 357 Chlorpromazine, 124, 330 Choline, 71, 330 Cholinergic, 198, 324, 331, 361 Chorea, 324, 331 Chromaffin System, 331, 341 Chromatin, 324, 331, 342, 361 Chromosomal, 50, 331 Chromosome, 331, 354 Chronic prostatitis, 67, 331 Circulatory system, 331, 341 Cirrhosis, 54, 217, 243, 263, 331
Clathrin, 331, 332, 342 Clear cell carcinoma, 331, 337 Clinical Competence, 99, 331 Clinical Medicine, 331, 368 Clinical Protocols, 67, 93, 331 Clinical study, 19, 34, 50, 331, 334 Clone, 36, 331 Cloning, 326, 331 Clozapine, 24, 332 CNS, 15, 39, 72, 91, 332 Coagulation, 326, 332, 348, 366 Coated Vesicles, 331, 332, 342 Coca, 332 Codeine, 35, 119, 201, 214, 332, 338, 363 Cofactor, 332, 369, 380 Cognition, 18, 149, 332, 360 Cognitive Therapy, 273, 332 Collagen, 321, 332, 345, 367 Colloidal, 320, 332, 341, 375 Colon, 333, 353, 354 Combination Therapy, 55, 333 Community Health Services, 29, 333 Comorbidity, 11, 23, 37, 96, 204, 228, 333 Complement, 14, 48, 52, 89, 322, 333, 366 Complementary and alternative medicine, 247, 254, 333 Complementary medicine, 247, 333 Complete remission, 333, 372 Compliance, 14, 54, 94, 101, 106, 115, 121, 234, 256, 333 Computational Biology, 293, 333 Computed tomography, 334, 374 Conception, 334, 344 Concomitant, 93, 262, 334 Condoms, 273, 279, 334 Conduction, 225, 334 Congestion, 324, 334 Conjugated, 334, 336 Consciousness, 320, 322, 334, 336, 337, 339, 370 Constipation, 3, 209, 317, 324, 334, 347 Constriction, 92, 321, 334 Consultation, 31, 334 Consumption, 9, 59, 69, 107, 119, 143, 153, 217, 334, 362, 373 Contamination, 54, 133, 334, 348 Continuous infusion, 174, 334 Contraindications, ii, 334 Control group, 64, 103, 334, 371 Controlled clinical trial, 58, 66, 72, 107, 110, 150, 334 Controlled study, 12, 17, 101, 119, 334
390 Methadone
Convulsions, 323, 334, 350 Coordination, 308, 330, 334 Coronary, 322, 329, 334, 335, 358 Coronary heart disease, 329, 334 Coronary Thrombosis, 335, 358 Corpus, 335, 355, 365, 368 Corpus Luteum, 335, 355, 368 Cortex, 335, 343, 372 Cortical, 81, 206, 243, 335, 343, 374 Cortices, 78, 335 Cortisol, 92, 117, 251, 320, 335 Cortisone, 335, 337 Cost-benefit, 30, 106, 335 Cost-Benefit Analysis, 30, 335 Cranial, 330, 335, 347, 365 Craniocerebral Trauma, 335, 347 Criterion, 47, 335 Cross-Sectional Studies, 85, 335 Cues, 48, 64, 335 Curative, 335, 361, 380 Cutaneous, 328, 335 Cyclic, 335, 347, 362 Cystitis, 66, 335 Cytochrome, 11, 59, 72, 91, 92, 114, 117, 136, 171, 172, 175, 179, 335, 336, 373 Cytochrome b, 336, 373 Cytokine, 43, 336 Cytoplasm, 324, 326, 336, 342, 346, 359, 361 D Data Collection, 44, 106, 336, 345 Decidua, 336, 366 Decontamination, 54, 206, 336 Degenerative, 336, 348, 359 Delavirdine, 12, 336, 362 Deletion, 324, 336 Delirium, 213, 324, 336 Delivery of Health Care, 336, 347 Delusions, 336, 370 Dementia, 324, 336 Demethylation, 140, 175, 337 Dendrites, 337, 361 Density, 51, 90, 330, 337, 344, 363, 376 Dentists, 191, 337 Depolarization, 337, 339 Depressive Disorder, 62, 96, 110, 158, 337, 354 Deprivation, 82, 337 Dermis, 337, 378, 381 DES, 170, 322, 337 Desensitization, 21, 133, 337 Designer Drugs, 219, 337
Desipramine, 49, 138, 153, 170, 337 DEXA, 177, 337 Dexamethasone, 283, 337 Dexmedetomidine, 20, 337 Dextroamphetamine, 321, 337, 358 Dextromethorphan, 52, 61, 69, 77, 116, 240, 264, 338 Diabetes Mellitus, 338, 348 Diagnostic procedure, 284, 338 Diaphragm, 338, 348, 373 Diastolic, 338, 347, 349 Diastolic blood pressure, 338, 347 Diclofenac, 142, 194, 338 Diclofenac Sodium, 338 Didanosine, 172, 282, 338 Dideoxyadenosine, 338 Digestion, 320, 326, 327, 338, 352, 355, 377, 383 Digestive system, 267, 338 Dilatation, 338, 368, 383 Dimethyl, 150, 219, 338, 353 Dipyridamole, 124, 338 Direct, iii, 8, 18, 33, 58, 76, 80, 88, 287, 331, 332, 338, 339, 349, 356, 364, 372, 379 Discrimination, 12, 18, 25, 35, 39, 40, 95, 339 Disease Progression, 53, 339, 384 Disinfectant, 339, 343 Disopyramide, 124, 143, 339 Disorientation, 336, 339 Disposition, 52, 72, 91, 92, 144, 153, 171, 182, 257, 259, 264, 339 Dissociation, 320, 339, 353 Distal, 339, 369 Distention, 67, 339 Disulfiram, 35, 107, 110, 144, 339 Dopa, 69, 339, 354 Dopamine Agonists, 94, 95, 339 Dorsal, 52, 339, 367 Dose-dependent, 135, 340, 385 Double-blind, 42, 43, 60, 76, 108, 116, 119, 126, 144, 145, 206, 240, 340 Drive, ii, vi, 17, 239, 340 Drug Combinations, 45, 340 Drug Interactions, 10, 19, 35, 45, 59, 70, 72, 91, 93, 104, 182, 264, 288, 340 Drug Monitoring, 104, 129, 150, 157, 181, 191, 204, 205, 207, 219, 228, 229, 231, 340 Drug Resistance, 34, 43, 340 Drug Tolerance, 340, 380 Drug Toxicity, 118, 340 Dynorphins, 340, 363
Index 391
Dyskinesia, 324, 340 Dysphoric, 337, 340 Dystonia, 324, 340 E Effector, 319, 333, 340 Ego, 340, 371 Elasticity, 59, 340 Elective, 215, 340 Electrolyte, 336, 341, 367, 376 Electrophoresis, 105, 129, 150, 215, 219, 341 Embryo, 326, 341, 351 Empirical, 33, 56, 57, 65, 70, 92, 97, 110, 341 Emulsion, 325, 341 Encephalitis, 40, 341 Encephalitis, Viral, 341 Endocarditis, 328, 341 Endocrine Glands, 341 Endocrine System, 53, 341, 360 Endocytosis, 49, 341 Endogenous, 15, 33, 49, 76, 79, 80, 87, 100, 101, 327, 339, 341, 342, 363 Endometrium, 336, 341, 357 Endopeptidases, 341, 369 Endorphin, 123, 124, 341 Endoscopic, 342, 358 Endosomes, 49, 341, 342 Endothelium, 342, 361 Endothelium-derived, 342, 361 Endotoxins, 333, 342 Enhancers, 102, 342 Enkephalins, 49, 342, 361, 363 Environmental Health, 292, 294, 342 Enzymatic, 321, 328, 333, 338, 342, 348 Enzyme Inhibitors, 342, 366 Eosinophils, 329, 342, 346, 354 Epidemic, 14, 35, 39, 46, 53, 110, 127, 167, 248, 342 Epidemiological, 55, 152, 342 Epidural, 134, 152, 342 Epinephrine, 320, 339, 342, 361, 362, 372, 382 Epithelial, 319, 336, 342, 348 Epithelial Cells, 342, 348 Ergot, 327, 342, 356 Escalation, 5, 22, 182, 242, 342 Esophagus, 338, 342, 377, 380 Estradiol, 104, 343 Estrogen, 343, 368 Ethanol, 5, 39, 41, 52, 60, 132, 343, 349 Ethinyl Estradiol, 104, 343
Etorphine, 49, 343 Euphoria, 20, 343 Evacuation, 334, 343, 354, 371 Evoke, 343, 377 Excitation, 330, 343, 344, 361 Excitatory, 52, 68, 325, 343, 346 Exhaustion, 322, 343 Exocytosis, 329, 343 Exogenous, 17, 70, 79, 341, 343 Extracellular, 341, 343, 358, 376 Extracellular Space, 343, 358 Extracorporeal, 154, 343 Extraction, 168, 190, 219, 343 Extrapyramidal, 320, 321, 324, 339, 343 Exudate, 343, 363 F Facial, 33, 343 Family Planning, 293, 343 Fat, 327, 335, 337, 343, 354, 376 Father-Child Relations, 31, 343 Fathers, 30, 98, 343 Fatigue, 42, 343 Fatty acids, 320, 343, 356 Feces, 334, 344, 377 Femoral, 152, 344 Femoral Fractures, 152, 344 Femur, 344 Fentanyl, 13, 20, 35, 61, 152, 174, 213, 282, 320, 344 Fetal Blood, 344, 366 Fetus, 11, 80, 271, 344, 356, 366, 368, 382 Fibrinogen, 344, 366, 380 Flatus, 344, 345 Flow Cytometry, 87, 344 Fluconazole, 104, 111, 159, 180, 262, 344 Flunitrazepam, 12, 39, 118, 249, 344 Fluorescence, 344 Fluorescent Dyes, 344 Fluorouracil, 338, 344 Fluoxetine, 101, 104, 109, 116, 157, 158, 169, 241, 344 Flushing, 339, 345 Fluvoxamine, 85, 158, 169, 204, 345 Focus Groups, 9, 31, 52, 57, 345 Fold, 17, 86, 345 Follow-Up Studies, 43, 58, 345 Forearm, 327, 345 Fourth Ventricle, 345, 355 Functional magnetic resonance imaging, 48, 81, 345 Fungus, 328, 342, 345
392 Methadone
G Gallbladder, 338, 345, 354 Gamma-Glutamyltransferase, 223, 345 Ganglia, 319, 345, 360, 365 Gas, 139, 140, 158, 207, 218, 234, 321, 328, 344, 345, 349, 361, 362, 370, 383 Gastric, 318, 327, 345, 348 Gastrin, 345, 349 Gastrointestinal, 327, 342, 343, 345, 360, 375, 378 Gastrointestinal tract, 343, 345, 375 Gelatin, 345, 346 Gene, 24, 36, 40, 52, 86, 104, 274, 326, 345, 346, 349, 367 Gene Expression, 52, 346 Genetics, 224, 346, 364 Genotype, 36, 86, 92, 114, 136, 346, 366 Gestation, 80, 346, 365, 366 Gestational, 51, 346 Gland, 100, 319, 320, 331, 335, 346, 364, 368, 369, 374, 377, 378 Glucocorticoid, 337, 346 Glucose, 76, 167, 327, 338, 346, 348, 350, 382 Glutamate, 49, 84, 338, 346 Glutamic Acid, 346, 361 Glycine, 52, 321, 346, 361 Glycoprotein, 11, 72, 91, 92, 124, 344, 346, 380 Gonad, 346 Gonadal, 53, 159, 346, 377 Governing Board, 346, 367 Government Agencies, 63, 346, 367 Graft, 346, 349, 351 Gram-negative, 346, 363 Gram-positive, 346, 363 Granulocytes, 346, 384 Granuloma, 19, 346, 347 Granulomatous Disease, Chronic, 347, 373 Growth, 15, 45, 54, 72, 100, 111, 190, 308, 319, 322, 323, 324, 329, 330, 347, 350, 352, 356, 363, 366, 382 Guanfacine, 150, 347 Guanine, 15, 347 Guanylate Cyclase, 347, 362 H Habitual, 18, 347 Halfway Houses, 90, 347 Hallucinogen, 347, 356, 366 Haptens, 320, 347, 371 Headache, 284, 347, 350 Headache Disorders, 347
Health Care Costs, 64, 347 Health Expenditures, 347 Health Services, 7, 19, 29, 34, 37, 38, 85, 103, 146, 226, 270, 336, 347 Health Status, 13, 39, 53, 64, 234, 347 Heart attack, 329, 347 Heme, 335, 336, 348 Hemoglobin, 206, 243, 322, 348 Hemorrhage, 335, 347, 348, 377 Hemostasis, 348, 375 Hepatic, 59, 73, 172, 257, 320, 336, 348 Hepatitis A, 47, 54, 348 Hepatocellular, 96, 348 Hepatocellular carcinoma, 96, 348 Hepatocytes, 55, 59, 348 Hepatoma, 55, 348 Hepatotoxic, 11, 348 Hepatotoxicity, 11, 348 Hepatovirus, 348 Heredity, 345, 346, 348 Heroin Dependence, 16, 69, 76, 126, 175, 348 Heterodimers, 63, 348 Heterogeneity, 320, 348 Hiccup, 330, 348 Histamine, 322, 324, 348, 368 HIV Protease, 91, 264, 349 HIV Protease Inhibitors, 91, 264, 349 Homologous, 349, 379 Hormonal, 53, 100, 349 Hormone, 53, 165, 167, 335, 337, 342, 343, 345, 349, 357, 368, 379 Host, 36, 56, 110, 328, 349, 350, 351, 382, 384 Human Genome Project, 50, 349 Hybrid, 331, 349 Hydrogen, 319, 326, 338, 349, 358, 363, 384 Hydrogenation, 326, 349 Hydromorphone, 20, 60, 80, 166, 174, 192, 233, 349 Hydroxyproline, 321, 332, 349 Hydroxytryptophol, 132, 349 Hyperalgesia, 60, 349 Hyperbaric, 233, 249, 349 Hyperbaric oxygen, 249, 349 Hypersensitivity, 93, 321, 337, 349 Hypertension, 329, 347, 349, 353 Hyperventilation, 79, 349 Hypnotherapy, 247, 350 Hypnotic, 350, 355, 358 Hypnotics and Sedatives, 329, 350 Hypoglycaemia, 336, 350
Index 393
Hypogonadism, 53, 350 Hypotension, 324, 334, 339, 350 Hypotensive, 76, 350 Hypoxia, 336, 350 I Ibogaine, 23, 350 Id, 245, 253, 300, 307, 314, 316, 340, 350 Illusions, 350, 374 Imagination, 320, 350 Imipramine, 62, 167, 350 Immune function, 87, 109, 167, 241, 350 Immune response, 319, 323, 335, 347, 350, 351, 378, 382, 384 Immune system, 4, 86, 87, 350, 351, 355, 359, 382, 384 Immunization, 350, 351, 375 Immunoassay, 121, 143, 207, 211, 350 Immunodeficiency syndrome, 270, 271, 273, 278, 294, 349, 350 Immunofluorescence, 51, 351 Immunogenic, 351, 371 Immunoglobulins, 351, 366 Immunologic, 34, 47, 136, 330, 349, 350, 351, 385 Immunology, 319, 320, 344, 351 Immunotherapy, 337, 351 Impairment, 32, 42, 121, 131, 176, 336, 340, 351, 357, 370 Impotence, 351, 364, 384 In situ, 20, 351 In vitro, 12, 21, 55, 59, 73, 80, 95, 105, 142, 169, 193, 224, 282, 351, 377, 380 In vivo, 12, 20, 54, 55, 59, 73, 80, 87, 241, 242, 338, 351, 358 Incision, 351, 353 Indicative, 78, 351, 364, 383 Indinavir, 12, 73, 351 Induction, 11, 19, 59, 91, 170, 187, 225, 324, 351, 353, 368 Infancy, 99, 202, 351 Infarction, 187, 335, 351, 358 Infertility, 327, 351 Inflammation, 81, 320, 323, 325, 331, 335, 341, 343, 348, 351, 357, 367, 369, 383 Infusion, 19, 33, 134, 156, 352 Ingestion, 107, 352, 367 Inhalation, 5, 348, 352, 367 Initiation, 21, 23, 36, 74, 75, 78, 137, 197, 352 Inotropic, 339, 352 Inpatients, 116, 185, 240, 270, 352, 375 Insecticides, 352, 384
Insight, 61, 84, 105, 352, 373 Insomnia, 11, 82, 250, 352, 382 Instillation, 67, 352 Intensive Care, 61, 156, 194, 221, 243, 352 Intercostal, 352, 373 Interferon, 55, 96, 205, 263, 352 Interferon-alpha, 205, 352 Interindividual, 163, 173, 211, 352 Intermittent, 80, 352, 355, 372 Interneurons, 21, 352 Interstitial, 66, 343, 352, 372 Intestinal, 72, 179, 352, 356 Intestine, 327, 352, 353 Intoxication, 17, 97, 131, 188, 336, 352, 384 Intracellular, 63, 331, 351, 352, 357, 362, 367, 372 Intracellular Membranes, 352, 357 Intramuscular, 84, 352, 364 Intravesical, 67, 353 Intrinsic, 12, 36, 95, 320, 353 Invasive, 223, 353, 356 Ion Channels, 21, 353, 379 Ionization, 140, 176, 205, 353 Ions, 325, 339, 341, 349, 353, 376 Iris, 353, 371 Isoniazid, 113, 231, 240, 244, 353 Isradipine, 77, 353 J Joint, 30, 91, 270, 353, 378 K Kb, 292, 353 Ketamine, 221, 301, 353, 366 Ketoconazole, 5, 59, 175, 353 Kinetic, 59, 74, 353 L Labile, 333, 353 Lactation, 75, 353, 368 Lamivudine, 226, 353 Large Intestine, 338, 352, 353, 372, 376 Latent, 234, 353 Lavage, 318, 354 Laxative, 209, 354 Lectin, 354, 357 Length of Stay, 7, 58, 354 Lentivirus, 348, 354 Lethal, 19, 176, 325, 354 Leukocytes, 326, 327, 330, 342, 346, 352, 354, 359, 361 Leukopenia, 354, 385 Levodopa, 339, 354 Levorphanol, 338, 354 Library Services, 314, 354
394 Methadone
Life cycle, 36, 354 Ligament, 354, 369 Ligands, 15, 18, 20, 24, 49, 80, 354, 372 Linear Models, 63, 354 Linkage, 37, 50, 354 Lip, 5, 354 Lipid, 331, 354, 358 Lithium, 324, 354 Lithotripsy, 154, 354 Liver cancer, 263, 355 Liver scan, 355, 374 Lobe, 355, 369 Lobule, 11, 355 Local Government, 355, 370 Localized, 351, 355, 366 Locus Coeruleus, 21, 191, 355 Longitudinal Studies, 335, 355 Longitudinal study, 57, 58, 77, 81, 90, 101, 355 Long-Term Care, 23, 46, 77, 355 Lorazepam, 18, 355 Lutein Cells, 355, 368 Lymph, 331, 342, 349, 355 Lymphadenopathy, 349, 355 Lymphatic, 342, 351, 355 Lymphocyte, 178, 188, 323, 355, 356 Lymphocyte Count, 178, 355 Lymphocyte Subsets, 188, 355 Lymphoid, 323, 356 Lysergic acid, 215, 356 Lysergic Acid Diethylamide, 215, 356 M Magnetic Resonance Imaging, 356, 374 Maintenance therapy, 14, 76, 115, 126, 140, 179, 183, 263, 356 Malignant, 193, 319, 355, 356 Mammary, 100, 356 Manic, 324, 354, 356, 370 Manifest, 52, 356 Marital Status, 294, 356 Mazindol, 49, 356 Meconium, 121, 356 Mediate, 13, 21, 48, 52, 80, 89, 100, 111, 190, 339, 340, 356 Mediator, 339, 356, 375 Medical Records, 356, 373 MEDLINE, 293, 356 Medullary, 338, 356 Meiosis, 356, 379 Melanin, 353, 355, 356, 382 Memantine, 69, 77, 84, 357
Membrane, 21, 49, 78, 332, 333, 337, 339, 341, 343, 346, 353, 357, 358, 359, 363, 366, 367, 376, 381 Membrane Proteins, 49, 357 Memory, 18, 259, 336, 357 Meninges, 329, 335, 357 Meningitis, 344, 357 Menopause, 85, 257, 357 Menstrual Cycle, 5, 357, 368 Menstruation, 321, 336, 357 Mental Disorders, 96, 267, 357, 369, 370 Mental Health Services, iv, 4, 66, 250, 295, 296, 303, 305, 306, 357 Mental Processes, 339, 357, 370 Mentors, 30, 45, 357 Meperidine, 337, 357 Mercury, 344, 357 Mesencephalic, 355, 357, 372 Mesolimbic, 51, 324, 357, 383 Meta-Analysis, 114, 133, 213, 243, 357 Methamphetamine, 69, 105, 219, 358 Methionine, 338, 358, 369, 378 Methylphenidate, 94, 95, 108, 251, 358 MI, 12, 13, 38, 63, 79, 127, 145, 224, 294, 318, 358 Microbe, 358, 381 Microbiology, 319, 325, 358 Microdialysis, 82, 101, 358 Microorganism, 332, 358, 384 Microscopy, 51, 358 Microsomal, 12, 358 Midazolam, 141, 358 Mitosis, 324, 358 Modeling, 52, 63, 105, 172, 358 Modification, 19, 248, 321, 337, 338, 358, 371, 384, 385 Molecule, 323, 326, 333, 339, 340, 342, 343, 354, 358, 363, 372, 381, 383 Monitor, 27, 37, 38, 44, 54, 64, 81, 121, 359, 362 Monoamine, 321, 323, 338, 359 Monocytes, 87, 354, 359 Mononuclear, 222, 346, 359 Mood Disorders, 223, 359 Motility, 148, 160, 359, 375 Motion Sickness, 359, 360, 368 Movement Disorders, 321, 324, 359 Mucilaginous, 356, 359 Mucins, 359, 373 Mucosa, 359, 368 Multidrug resistance, 91, 359 Mydriatic, 359, 384
Index 395
Myocardium, 322, 358, 359 Myoclonus, 187, 359 N Naive, 133, 178, 359 Naloxone, 13, 17, 20, 47, 51, 69, 84, 108, 109, 118, 123, 125, 156, 188, 240, 243, 244, 359 Naltrexone, 9, 12, 18, 23, 35, 48, 69, 94, 101, 106, 108, 109, 132, 133, 148, 150, 158, 191, 207, 231, 240, 241, 359 Narcolepsy, 337, 358, 359 Narcosis, 359, 360 Nausea, 323, 324, 339, 360, 364 NCI, 1, 266, 291, 360, 365 Needle Sharing, 214, 278, 294, 360 Needle-Exchange Programs, 211, 360 Nelfinavir, 12, 73, 360 Neonatal Abstinence Syndrome, 72, 217, 230, 244, 360 Neonatal period, 80, 360 Nerve, 22, 320, 322, 325, 330, 337, 355, 356, 360, 361, 367, 377, 381 Nervous System, 8, 15, 41, 87, 319, 320, 321, 326, 329, 332, 337, 340, 345, 346, 347, 354, 356, 358, 359, 360, 361, 365, 367, 375, 378, 379 Networks, 48, 91, 128, 198, 360 Neural, 80, 81, 84, 320, 337, 360, 376 Neuroendocrine, 100, 119, 360 Neuroleptic, 320, 323, 332, 360 Neurologic, 322, 349, 360 Neurology, 20, 33, 244, 359, 360 Neuronal, 22, 52, 78, 242, 359, 360, 361 Neuronal Plasticity, 52, 361 Neurons, 21, 52, 332, 337, 343, 345, 352, 354, 360, 361, 379 Neuropsychological Tests, 43, 361 Neuropsychology, 85, 361 Neurosecretory Systems, 341, 361 Neurosis, 361 Neurotic, 143, 322, 361 Neurotoxicity, 338, 361 Neurotoxin, 22, 361 Neurotransmitter, 25, 68, 84, 319, 321, 327, 339, 346, 348, 353, 361, 362, 378, 379 Neutrophils, 329, 346, 354, 361, 373 Nevirapine, 12, 73, 189, 199, 283, 361, 362 Niacin, 361, 382 Nicotine, 8, 15, 18, 31, 37, 69, 88, 104, 110, 149, 189, 218, 241, 361 Nitric Oxide, 35, 87, 361 Nitrogen, 218, 321, 362, 382
Nonmalignant, 193, 362 Non-nucleoside, 73, 199, 226, 336, 361, 362 Nonverbal Communication, 362, 370 Norepinephrine, 320, 337, 339, 361, 362, 372 Nuclear, 48, 325, 362 Nuclear Medicine, 48, 362 Nuclei, 40, 356, 358, 362 Nucleic acid, 338, 362, 373, 384, 385 Nucleus, 79, 324, 326, 331, 335, 336, 342, 355, 356, 359, 361, 362, 369, 383 Nucleus Accumbens, 362, 383 Nursing Care, 362, 375 Nursing Staff, 47, 362 Nutritional Status, 170, 362 O Observational study, 4, 362 Obsessive-Compulsive Disorder, 345, 362 Odour, 324, 363 Ofloxacin, 54, 363 Opacity, 337, 363 Opioid Peptides, 49, 79, 340, 342, 363 Opium, 46, 359, 363, 364 Opportunistic Infections, 279, 363 Organ Culture, 363, 380 Organelles, 330, 331, 336, 359, 363 Orthostatic, 324, 363 Outpatient, 7, 17, 23, 28, 32, 37, 38, 42, 44, 46, 55, 70, 90, 95, 101, 108, 110, 122, 132, 133, 141, 168, 195, 196, 203, 243, 259, 270, 272, 275, 363 Ovary, 335, 343, 346, 363 Overdose, 20, 120, 129, 133, 139, 145, 155, 156, 184, 227, 231, 240, 262, 317, 363 Ovum, 335, 336, 346, 354, 363, 368 Ownership, 38, 363 Oxidation, 319, 335, 363 Oxycodone, 35, 61, 363 P Paediatric, 233, 364 Pain Threshold, 61, 364 Palliative, 120, 186, 211, 220, 242, 244, 364, 380 Pancreas, 338, 364 Panic, 345, 350, 364 Panic Disorder, 345, 350, 364 Papaverine, 363, 364 Parent-Child Relations, 66, 98, 364 Parenteral, 188, 196, 233, 364 Parkinsonism, 324, 354, 364 Partial remission, 364, 372 Parturition, 364, 368
396 Methadone
Patch, 104, 106, 142, 364, 381 Pathologic, 324, 326, 328, 334, 349, 364, 383 Pathologic Processes, 324, 364 Patient Education, 306, 312, 314, 318, 364 PDQ, 301, 364 Pelvic, 67, 365, 369 Pelvis, 319, 365, 382 Penicillin, 322, 365 Penis, 334, 365 Peptide, 49, 79, 321, 341, 345, 363, 365, 369 Perception, 52, 81, 365, 374 Percutaneous, 354, 365 Perfusion, 11, 48, 78, 350, 365 Perinatal, 130, 171, 198, 230, 257, 271, 365 Peripheral blood, 222, 352, 365 Peripheral Nervous System, 342, 361, 365, 378 Personality Disorders, 154, 210, 226, 365 Phagocytosis, 86, 365 Phantom, 181, 365 Pharmacists, 143, 221, 365 Pharmacodynamics, 72, 182, 199, 218, 365 Pharmacologic, 61, 73, 93, 108, 175, 322, 344, 365, 381 Pharmacotherapy, 14, 18, 22, 23, 24, 49, 51, 72, 80, 108, 124, 133, 137, 145, 152, 158, 365 Phenazopyridine, 54, 366 Phencyclidine, 5, 301, 366 Phenotype, 86, 92, 114, 366 Phenyl, 339, 357, 366 Phosphorous, 82, 366 Phosphorus, 78, 128, 218, 328, 366 Phosphorylation, 51, 63, 366 Physicochemical, 11, 366 Physiologic, 320, 339, 357, 359, 366, 372 Pilot Projects, 100, 366 Pilot study, 7, 9, 26, 28, 42, 48, 65, 74, 85, 89, 99, 109, 115, 128, 148, 157, 217, 366 Placenta, 11, 193, 343, 344, 366, 368 Placental tissue, 11, 366 Plants, 319, 321, 328, 330, 332, 346, 354, 362, 366, 381 Plasma cells, 323, 366 Plasma protein, 92, 231, 320, 366, 375 Plasticity, 52, 367 Platelet Aggregation, 322, 361, 367 Platelets, 329, 361, 367 Pneumonia, 334, 367 Poisoning, 133, 156, 190, 232, 248, 336, 340, 342, 352, 357, 360, 367 Policy Making, 346, 367
Polymerase, 367, 373 Polyproteins, 349, 367 Pons, 327, 345, 367 Posterior, 322, 330, 339, 353, 364, 367 Postherpetic Neuralgia, 321, 367 Postnatal, 33, 188, 367 Postoperative, 93, 134, 173, 233, 357, 367 Post-synaptic, 21, 84, 367 Post-translational, 349, 367 Potassium, 21, 67, 367 Potentiate, 42, 367 Practicability, 367, 382 Practice Guidelines, 296, 367 Pravastatin, 104, 368 Precipitation, 176, 368 Preclinical, 12, 24, 42, 368 Precursor, 101, 331, 339, 340, 342, 349, 354, 362, 368, 382 Premedication, 194, 368 Prenatal, 33, 58, 80, 141, 142, 149, 169, 202, 242, 252, 341, 368 Presynaptic, 361, 368, 379 Prevalence, 39, 46, 53, 57, 67, 104, 108, 161, 164, 169, 178, 202, 203, 204, 228, 272, 368 Preventive Health Services, 333, 368 Probe, 73, 358, 368 Problem Solving, 27, 368 Progesterone, 124, 368, 377 Prognostic factor, 204, 368, 378 Progression, 45, 53, 269, 322, 368 Progressive, 32, 61, 83, 262, 331, 337, 340, 342, 347, 368, 372 Projection, 352, 362, 368, 372, 383 Prolactin, 100, 221, 327, 368 Promethazine, 194, 368 Pro-Opiomelanocortin, 363, 368 Prophase, 369, 379 Prophylaxis, 369, 373, 382 Proportional, 19, 369 Prospective study, 46, 89, 116, 120, 197, 214, 222, 249, 253, 355, 369 Prostate, 283, 331, 369 Prostate gland, 331, 369 Prostatitis, 67, 369 Protease Inhibitors, 11, 57, 64, 73, 104, 171, 208, 264, 369 Protein C, 35, 51, 320, 321, 332, 369, 382 Protein S, 274, 326, 369 Proteolytic, 333, 344, 369 Protocol, 7, 16, 17, 24, 27, 62, 63, 68, 99, 295, 369 Proximal, 19, 33, 152, 339, 368, 369
Index 397
Pruritus, 368, 369 Psychic, 357, 361, 369, 370, 374 Psychomotor, 12, 42, 69, 336, 360, 370 Psychopathology, 48, 77, 89, 99, 101, 370 Psychophysics, 93, 370 Psychophysiology, 361, 370 Psychosis, 205, 323, 346, 370 Psychotherapy, 36, 77, 98, 160, 205, 247, 249, 270, 275, 332, 370 Psychotomimetic, 321, 338, 370 Psychotropic, 47, 123, 370 Psychotropic Drugs, 123, 370 Puberty, 100, 370 Public Assistance, 62, 66, 370 Public Housing, 271, 370 Public Policy, 161, 278, 293, 370 Pulmonary, 15, 327, 334, 349, 370, 380, 383 Pulmonary Artery, 327, 370, 383 Pulmonary Ventilation, 349, 370 Pulse, 318, 359, 370 Pupil, 74, 359, 371 Purgative, 354, 371 Q Quality of Life, 34, 53, 67, 126, 141, 371, 378 R Race, 92, 134, 294, 337, 339, 371 Racemic, 92, 134, 337, 339, 371 Radiation, 322, 325, 335, 337, 344, 349, 365, 371, 374, 384 Radioactive, 325, 327, 336, 349, 353, 355, 362, 371, 374 Radioimmunoassay, 140, 206, 371 Radiolabeled, 80, 371 Radiology, 362, 371 Random Allocation, 371 Randomization, 25, 37, 90, 110, 371 Randomized clinical trial, 25, 35, 47, 67, 85, 97, 99, 249, 371 Reagent, 87, 143, 371 Reality Testing, 121, 370, 371 Receptor, 3, 5, 12, 15, 16, 18, 20, 21, 22, 25, 35, 36, 41, 49, 50, 51, 52, 63, 68, 69, 79, 83, 84, 95, 100, 124, 129, 224, 242, 251, 319, 323, 328, 330, 332, 338, 339, 371, 372, 375 Receptors, Adrenergic, 337, 372 Receptors, Serotonin, 372, 375 Recombinant, 263, 372, 383 Rectum, 324, 327, 333, 338, 344, 345, 353, 369, 372 Red Nucleus, 372, 383
Reductase, 368, 372 Refer, 1, 333, 352, 359, 360, 370, 372, 381 Reference point, 54, 372 Refraction, 372, 377 Refractory, 83, 174, 181, 197, 284, 372 Refractory cancer, 181, 372 Regimen, 7, 25, 53, 100, 331, 340, 365, 372 Reinfection, 54, 372 Reinforcement Schedule, 28, 372 Reliability, 32, 54, 86, 96, 211, 223, 372 Remission, 90, 263, 356, 372 Renal Circulation, 327, 372 Renal failure, 336, 372 Replicon, 55, 372 Research Design, 6, 7, 42, 48, 77, 373 Respiration, 328, 330, 359, 373 Respiratory Burst, 87, 373 Respiratory distress syndrome, 124, 373 Respiratory Muscles, 79, 373 Retrospective, 145, 192, 213, 230, 373 Retrospective study, 145, 373 Reverse Transcriptase Inhibitors, 11, 73, 104, 373 Ribavirin, 55, 373 Ribonuclease, 52, 373 Rifabutin, 175, 373 Risk factor, 46, 52, 54, 57, 61, 77, 214, 272, 369, 373 Risk-Taking, 107, 146, 165, 201, 373 Ritalin, 251, 373 Ritonavir, 12, 57, 73, 91, 117, 137, 147, 176, 227, 264, 282, 373 Role Playing, 294, 373 S Saccharin, 5, 373 Saliva, 150, 158, 214, 218, 373, 374 Salivary, 338, 373, 374 Salivary glands, 338, 373, 374 Saquinavir, 12, 57, 73, 147, 264, 374 Scans, 71, 78, 374 Scatter, 365, 374 Schizoid, 374, 384 Schizophrenia, 24, 95, 374, 383, 384 Schizotypal Personality Disorder, 374, 384 Screening, 20, 46, 49, 76, 88, 215, 219, 232, 256, 270, 282, 295, 304, 331, 364, 374, 382 Secretion, 100, 165, 327, 348, 353, 359, 374, 383 Secretory, 329, 374, 379 Secretory Vesicles, 329, 374 Sedative, 18, 123, 224, 332, 337, 343, 350, 355, 358, 368, 374
398 Methadone
Sedatives, Barbiturate, 325, 374 Sediment, 374, 382 Segmental, 54, 374 Segmentation, 374 Seizures, 336, 374 Self Administration, 108, 374 Semen, 369, 374 Semisynthetic, 327, 343, 356, 363, 375 Sensibility, 322, 349, 375 Septic, 325, 375 Seroconversion, 137, 147, 375 Serologic, 350, 375 Serotonin, 101, 324, 328, 332, 337, 344, 345, 356, 361, 366, 372, 375, 382 Sertraline, 23, 224, 375 Serum, 11, 53, 150, 151, 170, 215, 216, 219, 320, 322, 333, 371, 375 Serum Albumin, 371, 375 Sex Characteristics, 319, 370, 375, 379 Sexual Partners, 271, 375 Sexually Transmitted Diseases, 46, 375 Shedding, 82, 375 Shock, 154, 354, 359, 375, 381 Signs and Symptoms, 61, 95, 372, 375 Skeleton, 344, 353, 375 Skilled Nursing Facilities, 184, 375 Skull, 335, 375, 379 Sleep Deprivation, 82, 376 Small intestine, 349, 352, 376 Smoking Cessation, 8, 104, 173, 193, 234, 271, 328, 376 Smooth muscle, 322, 327, 348, 353, 359, 364, 376, 378 Sneezing, 375, 376 Social Behavior, 80, 208, 256, 376 Social Environment, 371, 376 Social Support, 55, 259, 376 Social Work, 31, 50, 58, 258, 260, 273, 376 Sodium, 20, 338, 376, 378, 383 Sodium Channels, 376, 383 Soft tissue, 321, 327, 375, 376 Solvent, 304, 326, 343, 376 Sound wave, 334, 376 Spasticity, 318, 325, 376 Specialist, 58, 85, 278, 308, 376 Species, 80, 342, 348, 349, 354, 356, 358, 371, 376, 378, 380, 381, 384 Specificity, 48, 320, 341, 376 Spectroscopic, 71, 78, 82, 377 Spectrum, 67, 102, 353, 377 Spinal cord, 52, 242, 325, 327, 329, 330, 332, 342, 357, 360, 365, 377
Spirochete, 377, 379 Stabilization, 36, 42, 55, 82, 87, 201, 377 Stabilizer, 20, 377 Staging, 4, 117, 374, 377 Stavudine, 172, 282, 377 Steady state, 74, 377 Sterile, 26, 325, 360, 377 Steroid, 335, 377 Stimulant, 69, 95, 224, 272, 321, 337, 348, 358, 377 Stimulus, 12, 25, 35, 39, 40, 94, 340, 343, 353, 370, 377, 380 Stomach, 329, 338, 342, 345, 349, 354, 360, 376, 377 Stool, 333, 353, 377, 379 Stress, 86, 200, 277, 329, 335, 345, 360, 377 Stroke, 267, 292, 329, 377 Structure-Activity Relationship, 20, 377 Stupor, 360, 377 Subacute, 93, 351, 378 Subarachnoid, 345, 347, 378 Subclinical, 351, 374, 378 Subcutaneous, 177, 220, 283, 364, 378 Subspecies, 376, 378 Substance P, 358, 374, 378 Substrate, 11, 72, 342, 378 Sulfur, 353, 358, 378 Superoxide, 373, 378 Supplementation, 320, 378 Support group, 62, 271, 378 Supportive care, 364, 378 Suppression, 34, 43, 163, 222, 378, 385 Suppressive, 86, 378 Supraspinal, 325, 378 Survival Analysis, 201, 378 Sweat, 139, 150, 337, 350, 378 Sweat Glands, 337, 378 Sympathomimetic, 321, 337, 339, 342, 358, 362, 378 Symphysis, 330, 369, 378 Symptomatic, 78, 262, 263, 321, 322, 378 Symptomatic treatment, 321, 322, 378 Symptomatology, 14, 42, 71, 99, 118, 195, 196, 243, 379 Synapse, 320, 337, 368, 379, 381 Synapsis, 379 Synaptic, 21, 50, 361, 379 Synaptic Transmission, 361, 379 Synergistic, 368, 379 Syphilis, 116, 379 Systemic, 19, 61, 63, 72, 105, 288, 327, 328, 336, 339, 342, 351, 379
Index 399
Systolic, 347, 349, 379 T Tardive, 324, 379 Telencephalon, 325, 379 Temperament, 50, 65, 379 Temporal, 34, 78, 347, 372, 379 Tendon, 376, 379 Tenesmus, 182, 242, 379 Terminator, 338, 379, 385 Testis, 343, 379 Testosterone, 53, 372, 379 Tetrahydrocannabinol, 328, 379 Therapeutic Community, 230, 271, 380 Thigh, 344, 380 Thoracic, 233, 338, 380 Thoracic Surgery, 233, 380 Thorax, 319, 321, 380 Threshold, 88, 145, 164, 178, 212, 349, 380 Thrombin, 344, 367, 369, 380 Thrombomodulin, 369, 380 Thrombosis, 196, 369, 377, 380 Thrush, 328, 380 Tidal Volume, 350, 380 Tin, 242, 243, 244, 380 Tissue Culture, 36, 380 Tolerance, 12, 21, 22, 35, 39, 49, 52, 60, 61, 63, 70, 79, 88, 101, 193, 264, 328, 350, 380 Tomography, 76, 251, 334, 374, 380 Tone, 347, 376, 380 Tooth Preparation, 319, 380 Topical, 343, 381 Toxic, iv, 15, 326, 343, 348, 356, 361, 381, 385 Toxicity, 11, 156, 177, 220, 283, 340, 357, 366, 381 Toxin, 380, 381 Trace element, 380, 381 Tractus, 79, 381 Tranquilizing Agents, 329, 370, 381 Transcriptase, 199, 226, 319, 336, 338, 353, 361, 362, 373, 377, 381, 385 Transdermal, 106, 142, 153, 213, 381 Transfection, 326, 381 Transferases, 59, 381 Translation, 258, 321, 381 Translational, 93, 381 Transmitter, 319, 339, 353, 356, 362, 381 Transplantation, 177, 182, 350, 381 Trauma, 65, 86, 336, 381 Treatment Failure, 46, 72, 96, 381 Triazolam, 12, 382 Tricyclic, 323, 337, 350, 356, 382
Trigger zone, 324, 382 Trimeprazine, 194, 382 Tryptophan, 101, 332, 375, 382 Tuberculostatic, 353, 382 Tyrosine, 339, 382 U Unconscious, 322, 350, 382 Urea, 378, 382 Ureter, 354, 382 Urethra, 365, 369, 382 Urinalysis, 47, 90, 109, 111, 125, 132, 133, 382 Urinary, 115, 117, 121, 129, 132, 154, 215, 219, 232, 325, 335, 366, 382 Urinary tract, 325, 366, 382 Urine Testing, 52, 139, 150, 382 Urodynamic, 67, 382 Uterus, 335, 336, 341, 357, 368, 382, 383 V Vaccination, 25, 203, 382 Vaccine, 25, 319, 369, 382 Vacuoles, 341, 363, 383 Vagina, 328, 337, 357, 383 Vaginitis, 328, 383 Valproic Acid, 111, 159, 383 Vascular, 327, 337, 342, 347, 351, 353, 361, 366, 383 Vasodilation, 339, 364, 383 Vasodilator, 327, 339, 348, 364, 383 VE, 109, 278, 383 Vector, 67, 383 Vein, 352, 362, 383 Venereal, 379, 383 Venlafaxine, 68, 383 Venous, 369, 383 Venter, 383 Ventral, 48, 82, 362, 367, 383 Ventral Tegmental Area, 48, 383 Ventricle, 362, 370, 371, 379, 383 Ventricular, 19, 163, 383 Venules, 327, 328, 383 Verapamil, 155, 383 Vertebrae, 377, 383 Vesicular, 358, 383 Veterinary Medicine, 293, 383 Viral, 34, 36, 43, 46, 53, 262, 301, 338, 341, 349, 384, 385 Viral Hepatitis, 46, 263, 301, 384 Viral Load, 43, 53, 384 Virulence, 381, 384 Vital Statistics, 63, 384 Vitro, 12, 55, 59, 384
400 Methadone
Vivo, 20, 55, 59, 73, 80, 105, 384 W Waiting Lists, 103, 384 Wakefulness, 336, 384 War, 7, 330, 384 White blood cell, 192, 323, 354, 355, 356, 366, 384 X Xenobiotics, 11, 384 Xenograft, 322, 384
X-ray, 334, 337, 344, 362, 371, 374, 377, 384 Y Yawning, 360, 384 Yeasts, 328, 345, 366, 384 Yohimbine, 145, 251, 384 Z Zalcitabine, 353, 384 Zidovudine, 111, 159, 226, 263, 264, 284, 385 Zymogen, 369, 385
Index 401
402 Methadone
Index 403
404 Methadone
