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REFERENCE COPY FOR LIBRARY USE ONLY Marijuana and Health Report of a Study by a Committee of the INSTITUTE OF MEDICINE Division of Health Sciences Policy NATIONAL ACADEMY PRESS Washington, D.C. 1982 l-.roH MAR ° 31982 LIBRARY
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 competences 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 l970 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 both the Academy's l863 Congressional charter responsibility to be an advisor to the federal government, and its own initiative in identifying issues of medical care, research, and education. This study was supported by the National Institutes of Health, Contract No. NOl-OD-0-2ll4. International Standard Book Number 0-309-03236-9 Library of Congress Catalog Card Number 8l-86534 Available from: NATIONAL ACADEMY PRESS 2l0l Constitution Ave., N.W. Washington, D.C. 204l8 Printed in the United States of America
COMMITTEE TO STUDY THE HEALTH-RELATED EFFECTS OF CANNABIS AND ITS DERIVATIVES Arnold S. Relman, Chairman Editor The New England Journal of Medicine Konrad E. Bloch Professor Department of Chemistry Harvard University Barton Childs Professor of Pediatrics and Biology The Johns Hopkins University School of Medicine Michael I. Cohen Chairman and Professor Department of Pediatrics Albert Einstein College of Medicine Montefiore Hospital and Medical Center P. B. Dews Professor of Psychiatry and Psychobiology Laboratory of Psychobiology Harvard Medical School Edward F. Domino Professor Department of Pharmacology University of Michigan Robert B. Edgerton Professor Departments of Psychiatry and Anthropology University of California, Los Angeles Daniel D. Federman Dean for Students and Alumni Harvard Medical School Irwin Feinberg Professor of Psychiatry University of California, San Francisco and Veterans Administration Medical Center, San Francisco Alfred P. Fishman Professor of Medicine Director Cardiovascular Pulmonary Division Hospital of the University of Pennsylvania Beatrix Hamburg Associate Professor of Psychiatry Department of Psychiatry and Department of Social Medicine and Health Policy Harvard Medical School H. Carl Haywood Professor of Psychology and Neurology Director The John F. Kennedy Center for Research on Education and Human Development Vanderbilt University Reese T. Jones Professor of Psychiatry Langley Porter Psychiatric Institute University of California, San Francisco Harold Kalant Professor Department of Pharmacology University of Toronto ill
Denise Kandel Professor of Public Health Department of Psychiatry Columbia University and New York State Psychiatric Institute Barbara M. Korsch Professor of Pediatrics and Head Division of General Pediatrics Children's Hospital of Los Angeles University of Southern California School of Medicine Robert Y. Moore Professor and Chairman Department of Neurology State University of New York at Stony Brook Robert F. Murray, Jr. Professor of Pediatrics, Medicine and Oncology Chief, Division of Medical Genetics Department of Pediatrics and Child Health College of Medicine Howard University Norton Nelson Professor of Environmental Medicine New York University Medical Center Charles P. O'Brien Professor of Psychiatry University of Pennsylvania School of Medicine and Philadelphia Veterans Adminis- tration Medical Center Sheldon J. Segal Director Population Sciences Division Rockefeller Foundation Paul D. Stolley Professor Department of Medicine University of Pennsylvania School of Medicine iv
INSTITUTE OF MEDICINE Frederick C. Robbins President Study Staff Enriqueta C. Bond, Director, Division of Health Sciences Policy Linda S. Dujack, Study Director Kathryn G. King, Research Associate Caren M. Carney, Research Associate Allyn M. Mortimer, Research Assistant Roszel S. Thomsen II, Research Assistant Linda A. DePugh, Administrative Secretary Constance V. Shuck, Administrative Secretary With the collaboration of the Director of the Division of Mental Health and Behavioral Medicine, Fredric Solomon, and the assistance of Institute of Medicine staff members Barbara Filner, Barbara Mandula, and Robert Field. Consultants Henry D. Abraham, Harvard University Richard E. Belleville, Private Consultant Kevin Fehr, Addiction Research Foundation Herbert Moskowitz, Southern California Research Institute Wendy Nelson, University of Pennsylvania Oakley S. Ray, Veterans Administration Medical Center Brian L. Strom, University of Pennsylvania
Study of the Health-Related Effects of Cannabis and Its Derivatives PANELS Cardiovascular and Respiratory Issues Alfred P. Pishman*, Chairman Brian F. Hoffman Professor and Chairman Department of Pharmacology Columbia University College of Physicians and Surgeons Jerome I. Kleinerman Chairman Department of Pathology Mount Sinai School of Medicine Gerard M. Turino Professor of Medicine Department of Medicine Columbia University College of Physicians and Surgeons Neurobiological Issues Irwin Feinberg*, Chairman Edward F. Domino* H. Craig Heller Associate Professor of Biology Department of Biological Sciences Stanford University Reese T. Jones* Harold Kalant* Irwin H. Krakoff Director Vermont Regional Cancer Center A. Edward Maumenee Professor of Ophthalmology Wilmer Institute Johns Hopkins Hospital Robert Moore* Charles P. O'Brien* *Committee member. vi
Behavioral, Psychosocial, and Epidemiologic Issues Charles P. O'Brien* and H. Carl Haywood*, Co-Chairmen Michael I. Cohen* Denise Kandel* Robert B. Edgerton* Barbara M. Korsch* Beatrix Hamburg* Paul D. Stolley* Reese T. Jones* Reproductive and Fetal Issues Daniel D. Federman*, Chairman F. Clarke Fraser Norton Nelson* Director of Medical Genetics Montreal Children's Hospital Sheldon Segal* Genetic, Oncogenic, and Cytogenetic Issues Barton Childs*, Chairman Arthur D. Bloom Robert F. Murray, Jr.* Professor of Pediatrics and of Human Genetics and Development Norton Nelson* Director, Clinical Genetics Columbia University College of Physicians and Surgeons Dietrich Hoffmann Associate Director Naylor Dana Institute for Disease Prevention Cell Biology, Pharmacology, and Immunological Issues P. B. Dews*, Chairman Konrad E. Bloch* Peter H. Schur Professor of Medicine Reese T. Jones* Harvard University Brigham and Women's Hospital Louis Lemberger Director of Clinical Pharmacology Lilly Laboratory for Clinical Research *Committee member. vii
ACKNOWLEDGMENTS Many persons outside the Institute of Medicine provided helpful suggestions, timely observations, and data bearing on the complex scientific, clinical, and societal issues that were being explored by the committee and staff. We wish especially to express our gratitude for contributions made by Monique Braude, Jacqueline Ludford, Robert Petersen, William Pollin, and Marvin Snyder of the National Institute on Drug Abuse; Edward Tocus and Stuart Nightingale of the Food and Drug Administration; the Interagency Committee to Monitor the Marijuana Study; Carl Leventhal of the National Institutes of Health and the chairman of the Interagency Committee; and Joseph Perpich of the National Institutes of Health, our project officer. We wish also to acknowledge the many scientists and others who responded to specific requests to review informally a portion of the draft report and those who, in general, gave their active assistance and collaboration: * C. Wayne Bardin, Population Council * Neal Benowitz, Langley Porter Psychiatric Institute * Albert Carlin, University of Washington * Sidney Cohen, Alcohol Research Center * Ellen Dempsey, McGill University * Everett Ellinwood, Duke University Medical Center Keith Green, Medical College of Georgia * Daniel Hoth, National Cancer Institute Lloyd Johnston, Institute for Social Research Louise Lev, National Cancer Institute Markku Linnoila, National Institute of Mental Health * Oriana Kalant and the Documentation Center of the Addiction Research Foundation * Edward Khantzian, Cambridge Hospital * Kaye Kilburn, University of Southern California School of Medicine * Warren Levinson, University of California, San Francisco * Raphael Mechoulam, School of Pharmacy, The Hebrew University, Israel * John Merritt, University of North Carolina ix
Akira Morishima, College of Physicians and Surgeons, Columbia University Al Munson, Medical College of Virginia Gabriel Nahas, College of Physicians and Surgeons, Columbia University William Paton, University of Oxford Bruce Petersen, Lilly Laboratory for Clinical Research Steven Podas, the Mount Sinai Medical Center Lee Robins, Washington University Medical School Harris Rosenkrantz, EG&G Mason Research Institute Donald Tashkin, University of California, Los Angeles David Taylor, Centers for Disease Control Carlton Turner, Senior Policy Adviser for Drug Policy, Office of Policy Development Arthur Zimmerman, University of Toronto
PREFACE This report is the work of the many people identified in the preceding pages, and to all of them I am very grateful. I particularly wish to thank my distinguished colleagues on the study committee, upon whose expert knowledge and critical judgment this report rests. They responded conscientiously to all the demands placed on them, and they did so with a promptness and grace that made my task easy. No study of this kind can be carried out without the help of a skilled staff. We were fortunate to have had the assistance of a devoted and highly capable staff team led by Enrigueta C. Bond and Linda S. Dujack. They coordinated the efforts of the committee, the panel, the consultants, and the Institute of Medicine staff, and they played the key role in keeping everything on schedule. Moreover, they carried out this formidable task with tact and common sense. On behalf of the committee, I wish publicly to acknowledge our indebtedness to the IOM staff, and I also wish to express my personal thanks to Drs. Bond and Dujack for their unfailing support and cooperation. Finally, I wish to acknowledge my appreciation of the editorial assistance of Wallace K. Waterfall, whose expert touch is evident throughout this document. Our aim was to write a report in "a clear and incisive form for the general public." Any success that we may have achieved is due in no small measure to his efforts. Arnold S. Relman, M.D. Chairman xi
CONTENTS SUMMARY l INTRODUCTION 6 l CHEMISTRY AND PHARMACOLOGY OF MARIJUANA l2 Cannabis Chemistry, l3 Pharmacology of Cannabis, l9 What is a Large or Small Cannabis Dose?, 23 General Toxicology, 24 Relevance of Nonhuroan Animal Models, 25 Cannabis Contaminants, 25 Cellular Toxicity, 26 Tolerance and Dependence, 26 Drug Interactions, 27 Summary and Conclusions, 28 Recommendations for Research, 28 References, 29 2 USE OF MARIJUANA IN THE UNITED STATES 34 Patterns and Trends of Use of Marijuana, 35 Summary, 50 Recommendations for Research, 52 References, 53 3 EFFECTS OF MARIJUANA ON THE RESPIRATORY AND CARDIOVASCULAR SYSTEMS 57 Respiratory System, 57 Cardiovascular System, 66 References, 73 4 EFFECTS OF MARIJUANA ON THE BRAIN 80 Brain Morphology, 80 Neurophysiology, 82 Epilepsy, 87 Neurochemistry, 87 Summary, 89 Recommendations for Research, 89 References, 90 xiii
EFFECTS OF MARIJUANA ON OTHER BIOLOGICAL SYSTEMS 94 Male Reproductive Function, 94 Female Reproductive Function, 97 Birth Defects and Teratogenicity, 99 Genetic Effects, l00 The Immune System, l03 Body Temperature, l04 Summary, l04 Recommendations for Research, l05 References, l06 BEHAVIORAL AND PSYCHOSOCIAL EFFECTS OF MARIJUANA USE ll2 Perceptual and Psychomotor Functions, ll3 Clinical Syndromes, l2l Summary, l28 Recommendations for Research, l29 References, l30 THERAPEUTIC POTENTIAL AND MEDICAL USES OF MARIJUANA l39 Glaucoma, l40 Antiemetic Action, l42 Appetite Stimulant, l45 Anticonvulsant Action, l45 Muscle Relaxant Action, l47 Antiasthmatic Effect, l47 Antianxiety Effect, l48 Antidepressant Effect, l49 Analgesic Action, l49 Alcoholism, l49 Opiate Withdrawal, l49 Antitumor Action, l50 Summary, l50 Recommendations for Research, l50 References, l5l FEDERAL SUPPORT OF RESEARCH ON MARIJUANA l56 Present Sources and Amounts of Support, l56 Areas of Research Support, l60 Summary of Findings, l64 Recommendations, l67 References, l68 APPENDICES l69 A WORK OF THE COMMITTEE l69 B ACCESS TO A-9-THC AND MARIJUANA FOR RESEARCH AND TREATMENT l7l C LONGITUDINAL STUDIES l75 D PARAQUAT ISSUE l86 xiv
Marijuana and Health
