PATHWAYS OF ADDICTION

OPPORTUNITIES IN DRUG ABUSE RESEARCH

Committee on Opportunities in Drug Abuse Research

Division of Neuroscience and Behavioral Health

INSTITUTE OF MEDICINE

NATIONAL ACADEMY PRESS
Washington, D.C. 1996



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Pathways of Addiction: Opportunities in Drug Abuse Research PATHWAYS OF ADDICTION OPPORTUNITIES IN DRUG ABUSE RESEARCH Committee on Opportunities in Drug Abuse Research Division of Neuroscience and Behavioral Health INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. 1996

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Pathways of Addiction: Opportunities in Drug Abuse Research NATIONAL ACADEMY PRESS 2101 Constitution Avenue, NW Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competencies and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. Support for this study was provided by the National Institute on Drug Abuse (contract no. N01 DA-3-8000). Library of Congress Cataloging-in-Publication Data Pathways of addiction : opportunities in drug abuse research / Committee on Opportunities in Drug Abuse Research, Division of Neuroscience and Behavioral Health, Institute of Medicine. p. cm. Includes bibliographical references and index. ISBN 0-309-05533-4 1. Substance abuse—Research—United States. 2. Substance abuse—Research—Government policy—United States. I. Committee on Opportunities in Drug Abuse Research. RC564.P365 1996 362.29'072073—dc20 96-30998 CIP Pathways of Addiction: Opportunities in Drug Abuse Research is available for sale from the National Academy Press, 2101 Constitution Avenue, NW, Box 285, Washington, DC 20055. 800-624-6242 or 202-334-3313 (in the Washington metropolitan area). http://www.nap.edu. Cover: Gloria Monteiro Rall, "Overlapping," with permission of the artist. Copyright 1996 by the National Academy of Sciences. All rights reserved. Printed in the United States of America. The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staalichemusseen in Berlin.

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Pathways of Addiction: Opportunities in Drug Abuse Research COMMITTEE ON OPPORTUNITIES IN DRUG ABUSE RESEARCH RICHARD J. BONNIE,* Chair, John S. Battle Professor of Law, University of Virginia School of Law, Charlottesville, Virginia JUDITH S. BROOK, Professor of Community Medicine, Mount Sinai School of Medicine, New York, New York RICHARD CLAYTON, Director, Center for Prevention Research, University of Kentucky, Lexington, Kentucky JOHN E. DONOVAN, Scientific Director, Pittsburgh Adolescent Alcohol Research Center, Western Psychiatric Institute and Clinic, and Associate Professor, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania MARIAN W. FISCHMAN, Professor of Behavioral Biology, College of Physicians and Surgeons of Columbia University, and Research Scientist, New York State Psychiatric Institute, New York, New York ROBERT E. FULLILOVE, III, Associate Dean for Community and Minority Affairs, Columbia University School of Public Health, New York, New York JAMES G. HAUGHTON,* Medical Director, Division of Public Health Programs and Services, Los Angeles County Department of Health Services, Los Angeles, California JAMES A. INCIARDI, Director, Center for Drug and Alcohol Studies, University of Delaware, Newark, Delaware GEORGE F. KOOB, Director, Division of Psychopharmacology, and Professor, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California MITCHELL B. MAX, Chief, Clinical Trials Unit, Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland ERIC J. NESTLER, Elizabeth Mers and House Jameson Professor, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut PATRICK M. O'MALLEY, Program Director, Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan PETER SELWYN, Associate Professor, Department of Internal Medicine, Epidemiology, and Public Health, Yale University School of Medicine, New Haven, Connecticut *   Member, Institute of Medicine.

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Pathways of Addiction: Opportunities in Drug Abuse Research BARBARA R. WILLIAMS, Vice President Emeritus, RAND, Washington, D.C. GEORGE E. WOODY, Clinical Professor of Psychiatry, University of Pennsylvania, and Chief, Substance Abuse Treatment Unit, Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania BARRY ZUCKERMAN, Professor and Chairman, Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts Special Advisors to the Committee LAURIE CHASSIN, Professor, Department of Psychology, Arizona State University, Tempe, Arizona MIRIAM DAVIS, Science and Health Policy Consultant, Silver Spring, Maryland JEFFREY FAGAN, Associate Professor, School of Criminal Justice, Rutgers University, New York, New York LINDA MAYES, Arnold Gesell Associate Professor of Child Development and Pediatrics, Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut KATHLEEN MERIKANGAS, Director, Genetic Epidemiology Research Unit, Yale University School of Medicine, New Haven, Connecticut DAVID MUSTO, Professor of Psychiatry and the History of Medicine, Yale University School of Medicine, New Haven, Connecticut JEFFREY SWANSON, Associate Professor, Psychiatric Epidemiology and Health Services Research Program, Duke University Medical Center, Durham, North Carolina STAFF CAROLYN E. FULCO, Study Director CATHARYN LIVERMAN, Program Officer CARRIE INGALLS, Research Assistant TERRI SCANLAN, Project Assistant CONSTANCE PECHURA, Director, Division of Neuroscience and Behavioral Health

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Pathways of Addiction: Opportunities in Drug Abuse Research Preface Drug abuse can be viewed from many perspectives. At different times and in different contexts, each of us uses multiple vocabularies to describe and discuss drug abuse. Sometimes we use the vocabulary of choice and responsibility. Sometimes we use the vocabulary of health and disease. Sometimes we use the marketplace vocabulary of supply and demand. Sometimes we use the vocabulary of crime and punishment. The list goes on. Scientific study cannot be expected to erase or reconcile fully our multiple understandings and interpretations of drug abuse. Were it not for scientific research, however, we would be unable to understand drug abuse from any of those perspectives. Were it not for scientific research, we would be unable to harness the social and political energy needed to respond to drug abuse in a rational manner. When the National Institute on Drug Abuse (NIDA) was established in 1974, the nation was grappling with a major epidemic of illicit drug use. As part of a multipronged national response to this problem, Congress made a significant investment in drug abuse research. Over the ensuing two decades, substantial advances have been made along numerous scientific paths, ranging from the discovery of endogenous opioids to an assessment of the impact of needle sharing on the transmission of HIV (human immunodeficiency virus) disease. As the primary federal funding agency for drug abuse research, NIDA deserves credit for stimulating and supporting the talented scientists who have moved the field for-

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Pathways of Addiction: Opportunities in Drug Abuse Research ward,1 for maintaining a coherent scientific agenda in the face of shifting political winds, and for building a strong foundation for continuing scientific progress in the years ahead. In January 1995, at NIDA's request, the Institute of Medicine (IOM) formed the Committee on Opportunities in Drug Abuse Research to assess current knowledge and accomplishments and to propose a research agenda for the next decade. The committee was asked to take a broad perspective, considering not only NIAD's research portfolio but any opportunity for increasing knowledge about drug abuse through research, for promoting effective prevention and treatment strategies, and for ameliorating the consequences of drug abuse and dependence. In order to fulfill this charge, the IOM selected for membership on the committee individuals with expertise in a variety of scientific disciplines who have conducted research on many fields of inquiry bearing on drug abuse, including neuroscience, clinical research and treatment, psychopharmacology, epidemiology, etiology, prevention, AIDS/HIV research, fetal and child development, public health, and law and public policy. During the course of the study, the committee met four times and solicited written suggestions and opinions from experts in a variety of fields. In conjunction with its meetings, the committee invited presentations from treatment experts, criminologists, individuals associated with community prevention programs and treatment centers, neuroscientists, behavioral scientists, and other interested persons (see Appendix A). The committee's primary charge was to identify directions for future research. The committee recognized, however, that the setting of research priorities is not a purely scientific task. Priorities must reflect a compound assessment of scientific opportunity and social significance. Scientific hunches must be filtered through social aspirations. In the end, judgments about research in the multiplicity of fields relating to drug abuse must be based on a shared conception of the goals of the nation's investment in drug abuse research. In light of the diverse perspectives and values that shape this field of research, it seems appropriate to set forth the committee's own perspective on its task. In the committee's view, scientific research pertaining to drug abuse is most usefully organized and evaluated within a public health framework. The ultimate aim of the nation's investment in drug abuse research is to enable society to take more effective measures to prevent abuse of and dependence on harmful drugs (e.g., alcohol, nicotine, cocaine, opi- 1   Other sources of research support include the National Institute on Mental Health, the National Institute on Alcohol Abuse and Alcoholism, the Substance Abuse and Mental Health Services Administration (SAMHSA), and the Department of Justice. However, NIDA supports 85 percent of the world's research on drug abuse and addiction.

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Pathways of Addiction: Opportunities in Drug Abuse Research ates) and to reduce the harmful individual and social consequences associated with abuse and dependence. The menu of potentially useful societal interventions encompasses those available for any public health problem, including actions focused on the host (user), agent (drug), and environment (setting). This is not to say that the public health perspective is the only way to think about drug abuse, for as noted, drug abuse can be interpreted and understood from many perspectives. However, a public health framework is well suited to the task because it is comprehensive enough to incorporate many diverse fields of scientific inquiry and supple enough to embrace almost all policy positions that people hold about drug abuse control. Another virtue of the public health paradigm is that it encompasses and integrates strategies of "demand reduction" and "supply reduction" that are too often used to bifurcate drug abuse prevention programs. At first glance, those categories seem to fit well within a public health paradigm: supply reduction strategies aim to reduce the availability of abusable drugs (the agent), whereas demand reduction strategies aim to reduce the "host's" drug-using behavior. From an empirical perspective, however, the usefulness of this dichotomy is limited. Most importantly, it fails to encompass strategies explicitly designed to ameliorate the consequences of abuse and dependence. Also, in practice, those terms are usually defined to put all ''law enforcement" research in the supply reduction category and all "health" research in the demand reduction category. That misleading practice creates fiscal and conceptual impediments to a comprehensive research agenda because it signals a division of effort between the research-sponsoring agencies in the Departments of Justice and of Health and Human Services. For example, even though legal sanctions aimed at users are a key part of the societal effort to reduce demand for illicit drugs, the behavioral effects of legal sanctions are rarely included in a research agenda for "prevention" or demand reduction. Similarly, because efforts to suppress the availability of controlled substances are seen as supply reduction, the actual effects of those efforts on the prevalence and social consequences of drug abuse tend to be ignored, as do the effects of controlled substance regulation on legitimate medical practice. A public health perspective provides criteria of relevance and a framework for assessing priorities. Drawing on that perspective, the committee decided to include within its vision any fields of inquiry that, if productive, could enable the nation to reduce the individual and social costs of drug abuse. More specifically, the "field" of drug abuse research encompasses research designed to enhance our understanding of (1) the nature and scope of drug abuse and dependence; (2) the causes and consequences of drug abuse and dependence; and (3) the efficacy and costs of interven-

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Pathways of Addiction: Opportunities in Drug Abuse Research tions aimed at reducing drug abuse and dependence and ameliorating its adverse consequences. The nation's drug abuse policy has been subject to persistent debate for 75 years. Awareness of the continuing controversy led the committee to think about the relationship between drug abuse research and drug abuse policy. History teaches that the drug abuse research agenda is inevitably shaped by prevailing assumptions and values, especially those embedded in existing public policies and laws (see Appendix B). At one level, this is altogether appropriate; after all, drug abuse research is primarily a public investment, and the social value of proposed research is properly influenced by public opinion and judged by politically accountable decisionmakers. At the same time, open mindedness is a sine qua non of scientific progress. In all value-charged areas of scientific research, including drug abuse, scientists must always be prepared to ask whether important and potentially fruitful avenues of inquiry are being foreclosed because they are not "politically correct." In this spirit of critical reflection, the committee has asked whether and to what extent the goals of drug abuse research are circumscribed by existing social policies. Use of unprescribed opiates, cocaine, and other "controlled substances" is prohibited by law. In common parlance, the term "drug abuse" typically refers to any use of those drugs, whereas nicotine and alcohol are generally not regarded as drugs at all, much less drugs of abuse. However, the committee questioned whether the objectives of drug abuse research differ from the objectives of research concerning nicotine and alcohol. In the committee's view, the answer is no. Differences in the legal status of these substances do not require or entail separate research agendas; to the contrary, differences in legal controls present specific researchable issues within the framework of a common public health research agenda. The ultimate goal of social policy for alcohol, nicotine, and controlled substances is to reduce the adverse health and social consequences associated with abuse of, or dependence on, these harmful drugs and thereby to reduce the staggering social costs associated with their use. The controversial policy question is whether and to what extent society should aim to discourage or suppress use as a means of reducing abuse and dependence. In the context of alcohol, prevailing policy aims to suppress consumption by minors but does not aim to discourage "responsible use" by adults. In the context of nicotine, national policy aims to suppress use by minors and is moving toward a policy of regulatory discouragement for adults. In the context of prohibited drugs, prevailing policy aims to suppress use by everyone as a means of preventing abuse. In all three contexts, however, the aim of scientific research is the same: to advance our knowledge regarding the causes and consequences of using these drugs; to determine the best methods (including prevention of both initiation

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Pathways of Addiction: Opportunities in Drug Abuse Research and escalation of use) for minimizing adverse consequences; and to determine the benefits and costs of alternative strategies for reducing abuse and dependence. During the course of its deliberations, the committee also discussed the issue of so-called root causes that repeatedly surfaces in contemporary public debate about crime, drug abuse, and other social problems. Some members believe that a major national commitment to improve the social and economic conditions of the disintegrating and impoverished communities of this country—to enhance educational opportunities, to create jobs, to protect children, and generally, to nurture hope where there is now despair—would substantially reduce drug abuse and other symptoms of social distress. Other committee members are not so sanguine about the preventive impact of such an investment, pointing out that the existing etiological research does not provide strong scientific support for the root cause hypothesis. In the end, the debate about root cause turns as much on political philosophy as it does on empirical evidence, and definitive answers are unlikely to be produced by scientific investigation. However, reflection on this issue enriched the committee's understanding of the factors that should be taken into account in the design of a research agenda that is at once ambitious and realistic. No one thinks that drug abuse research can reasonably be expected to yield the "magic bullet"—a vaccine or a pharmacological cure—that would eliminate drug abuse and dependence in all individuals. Drug abuse is an endemic public health problem in modern societies, and it is a mistake, in the committee's opinion, for either policymakers or research scientists to promise more than they can achieve. At the same time, committee members are confident that a comprehensive research strategy, proceeding on all fronts of basic and applied research described in this report, can reasonably be expected to enable our nation to reduce drug abuse and dependence and to ameliorate its adverse social consequences. In the final analysis, the value of the investment in drug abuse research is measured in lives saved and reclaimed, in the success of each young person who stays in school and joins the work force, and in the happiness of each child nurtured by his or her parents rather than abused or abandoned by them. On the surface, this report is about the pursuit of opportunities in science; however, its real meaning can be seen in the faces of people who suffer, and cause others to suffer, because they use drugs. They are the beneficiaries of drug abuse research and of the recommendations presented in this report. Richard J. Bonnie, LL.B., Chair Committee on Opportunities in Drug Abuse Research

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Pathways of Addiction: Opportunities in Drug Abuse Research Acknowledgments The committee appreciates the expert support of the IOM project staff, division director, Division of Neuroscience and Behavioral Health, Constance Pechura, for her negotiating skills, practical comments, and guidance during the committee's deliberations. We thank study director, Carolyn Fulco, and program officer, Catharyn Liverman, for their contributions to the structure and substance of the report and in the editing of this document. We are indebted to Carrie Ingalls for her excellent research skills in collecting, analyzing, and presenting a range of information, in addition to verifying all committee references; and project assistant, Terri Scanlan for providing logistical assistance for the workshop and all committee meetings, overseeing report production; and preparing the camera-ready copy of the report. The committee benefitted from the expertise of Deborah Beck, Laurie Chassin, Miriam Davis, Jeffrey Fagan, Linda Mayes, Kathleen Merikangas, Klaus Miczek, David Musto, and Jeffrey Swanson for their input into the committee's deliberations. The committee wishes to acknowledge the input of Douglas Anglin, Guardia Bannister, Thomas Crowley, Loretta Finnegan, Barry Glick, Elizabeth Griffin, Yifrah Kaminer, Herbert Kleber, Thomas Kosten, Nancy McLaughlin, Peter Reuter, and David Rosenbloom. The committee appreciates the copy editing by Paul Phelps and Florence Poillon; the assistance of Claudia Carl in guiding the report through review; and Mike Edington's assistance in report production. The IOM staff and the committee appreciate the thoughtful input and

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Pathways of Addiction: Opportunities in Drug Abuse Research contributions of Timothy Condon, Jean Comolli, and the staff at NIDA. We are also indebted to the reviewers whose comments greatly improved the quality of this document. We also wish to thank the many representatives of federal agencies, congressional staff, academia, advocacy groups, and professional organizations who shared their expertise with the committee. Those individuals are acknowledged in Appendix A.

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Pathways of Addiction: Opportunities in Drug Abuse Research Contents     EXECUTIVE SUMMARY   1 1   INTRODUCTION   13 2   BEHAVIORAL RESEARCH   35 3   NEUROSCIENCE   56 4   EPIDEMIOLOGY   94 5   ETIOLOGY   117 6   PREVENTION   139 7   CONSEQUENCES   159 8   TREATMENT   192 9   MANAGED CARE   222 10   DRUG CONTROL   250     APPENDIXES         A ACKNOWLEDGMENTS   279     B DRUG ABUSE RESEARCH IN HISTORICAL PERSPECTIVE   284     C DIAGNOSTIC CRITERIA   295     INDEX   299

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Pathways of Addiction: Opportunities in Drug Abuse Research PATHWAYS OF ADDICTION

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