MARIJUANA AS MEDICINE?

The Science Beyond the Controversy

ALISON MACK

JANET JOY

for the Institute of Medicine

NATIONAL ACADEMY PRESS
Washington, D.C.



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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy MARIJUANA AS MEDICINE? The Science Beyond the Controversy ALISON MACK JANET JOY for the Institute of Medicine NATIONAL ACADEMY PRESS Washington, D.C.

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, D.C. 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 Principal Investigators responsible for the original report were chosen for their special competences and with regard for appropriate balance. This book was supported by a grant to the Institute of Medicine by the Robert Wood Johnson Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s), and the Robert Wood Johnson Foundation does not take responsibility for any statements or views expressed. PRINCIPAL INVESTIGATORS AND ADVISORY PANEL FOR IOM REPORT: The following people served as principal investigators and advisors to the 1999 IOM report, Marijuana and Medicine: Assessing the Science Base, on which this book is based: JOHN A. BENSON, JR., co-Principal Investigator, Oregon Health Sciences University School of Medicine, Portland; STANLEY J. WATSON, JR., co-Principal Investigator, University of Michigan, Ann Arbor; STEVEN R. CHILDERS, Wake Forest University, Winston-Salem, North Carolina; J. RICHARD CROUT, Crout Consulting, Bethesda, Maryland; THOMAS J. CROWLEY, University of Colorado, Denver; JUDITH FEINBERG, University of Cincinnati Medical Center, Cincinnati, Ohio; HOWARD L. FIELDS, University of California in San Francisco; DOROTHY HATSUKAMI, University of Minnesota, Minneapolis; ERIC B. LARSON, University of Washington Medical Center, Seattle; BILLY R. MARTIN, Virginia Commonwealth University, Richmond; TIMOTHY VOLLMER, Yale School of Medicine, New Haven, Connecticut Library of Congress Cataloging-in-Publication Data Mack, Alison. Marijuana as Medicine? : the science beyond the controversy / Alison Mack, Janet Joy. p. cm. Includes bibliographical references and index. ISBN 0-309-06531-3 1. Marijuana—Therapeutic use. I. Joy, Janet E. (Janet Elizabeth), 1953-. II. Title. RM666.C266 M325 2000 615′.32345—dc21 00-046058 Additional copies of this report are available from National Academy Press,, 2101 Constitution Avenue, N.W., Lockbox 285, Washington, D.C. 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu Printed in the United States of America Copyright 2001 by the National Academy of Sciences. All rights reserved.

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy INSTITUTE OF MEDICINE Shaping the Future for Health

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy THE NATIONAL ACADEMIES National Academy of Sciences National Academy of Engineering Institute of Medicine National Research Council The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy ACKNOWLEDGMENTS Our chief debt as authors of this book is to its predecessor: the 1999 Institute of Medicine report, Marijuana and Medicine: Assessing the Science Base. Because this landmark study provided the foundation—indeed, the raison d'etre—for our own efforts, we must begin by acknowledging the many contributors who made Marijuana and Medicine an authoritative document, and one worthy of popularization. We are also indebted to many people who helped us adapt the Institute of Medicine study for lay readers. A variety of experts contributed supplemental information and answered questions raised in the original report. They include Roger Anderson, Daniel Brookoff, Daniel Nixon, and Andrew Watry, who provided perspectives on patient experiences during clinical trials of medical marijuana and Marinol®. Thanks also to Sue Rusche and Eric Voth for directing us toward these sources. Others responded to many requests for updated information about policy changes and plans for new clinical trials. They include Steve Gust, Tony Moffet, and Roger Pertwee. For our chapter on medical marijuana and the law, a subject only briefly mentioned in Marijuana and Medicine, we received abundant support and advice from Richard Bonnie and Eve Goldstein. Chuck Thomas, Dale Gieringer, and Scott Imler provided prompt, detailed, and thoughtful answers to our questions regarding cannabis buyer's clubs.

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy This book relies on the original Institute of Medicine report, which was very much a team effort, and we continue to be indebted to the excellent work of Deborah Yarnell and Amelia Mathis. It was first conceived of by Kenneth Shine, President of the Institute of Medicine, Karen Hein, who was Executive Director at the time, and Stephen Mautner, Executive Editor of the National Academy Press. We thank them for their sustained support and enthusiasm for the project. The Robert Wood Johnson Foundation provided financial support for the project. This book has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the Institute of Medicine in making its publications as sound as possible and to ensure that they meet institutional standards for objectivity and evidence. The authors wish to thank the following individuals for their participation in the review of this report: Jack D. Barchas, Weill Medical College of Cornell University, Ithaca, New York; John A. Benson, Jr., Oregon Health Sciences University School of Medicine, Portland; Richard J. Bonnie, University of Virginia, Charlottesville; Catherine A. Warren, North Carolina State University, Raleigh; Stanley J. Watson, Jr., University of Michigan, Ann Arbor; and Hallie Wilfert, Institute of Medicine, Washington, D.C. While the individuals listed above have provided constructive comments and suggestions, it must be emphasized that responsibility for the final content of this report rests entirely with the authors and the Institute of Medicine. We owe our editor Stephen Mautner enormous gratitude, most notably for his monumental patience when our initially straightforward project became a lengthy, complicated one. Also, since he was involved in this project from its earliest beginnings, we thank him for bringing us together as well as for keeping us there. Alison wishes to thank the many people whose hard work and kindness enabled her to complete this book, despite complications of pregnancy and its joyous, but chaotic, aftermath. They include the high-risk maternity and NICU nursing staff at

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy Christiana Hospital and her “extended family” at Wilmington Montessori School. Janet Joy inspired me with her scientific expertise and—sometimes more importantly—buoyed me with her infectious sense of humor. Words cannot express my gratitude for the limitless help and support I received during this adventure from my husband, Tony Kinney, and my mother, Marjorie Mack. Janet wishes to thank John Benson and Stan Watson, Principal Investigators of the original report. They were a “dream team”—grouchy when necessary, unfailingly supportive, and as intellectually honest as they were demanding. Alison Mack was the last addition to the dream team. She managed to keep this project, which grew larger than either of us envisioned, moving forward in the face of great difficulty. Alison Mack Janet Joy

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy CONTENTS     Preface   xi  I   MARIJUANA, MEDICINE, AND SCIENCE   1     1  Introduction   3     2  Can Marijuana Help?   13     3  How Harmful Is Marijuana?   38  II   MEDICAL MARIJUANA AND DISEASE   71     4  Marijuana and Pain   77     5  Marijuana and AIDS   86     6  Marijuana and Cancer   95     7  Marijuana and Muscle Spasticity   106     8  Marijuana and Neurological Disorders   115     9  Marijuana and Glaucoma   124  III   MEDICAL MARIJUANA IN CONTEXT   129     10  Pharmaceuticals from Marijuana   133     11  Legal Issues   156     12  Marijuana's Medical Future   173     Index   187

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy PREFACE In recent years there has been unprecedented interest in whether marijuana or its constituent compounds should be used as medicine. Since 1996 voters in eight states have approved the medical use of marijuana. These state ballot initiatives, and the wider discussion they spawned about appropriate national policies regulating marijuana, have been sharply divisive. Advocates of personal choice with a growing distrust of scientific medicine seek alternatives congruent with their values about health and life. Others dismiss medical marijuana as a subterfuge enabling liberalization, which they fear will spread the plague of drug abuse. Medical use might legitimize the drug as safe and effective and justify experimentation by susceptible young people. Both sides cite scientific evidence to support their views. The director of the White House Office of National Drug Control Policy (ONDCP) asked the Institute of Medicine (IOM) to review the evidence for the potential benefits and risks associated with the use of marijuana. The IOM is a non-governmental, apolitical, non-profit organization of scientists whose independence and objectivity lend credibility to its studies and recommendations. The report of the 18-month IOM study was first released to both the ONDCP and the public in March 1999.

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy The study team sought and obtained opinions from both sides of the debate, learned of many personal experiences from public hearings, cannabis clubs, and correspondence; anecdotes and opinions were carefully weighed. The team was also informed by dozens of consultant scientists, particularly those engaged in the striking recent advances in the molecular biology, pharmacology, neurochemistry, and social sciences. Exhaustive literature searches led to the citation of over 500 selected scientific papers related to the broad scope of the study. There is remarkable consensus about the fast-moving science that suggests the potential of cannabinoid drugs for medical use. There are far less convincing data about proven medical benefits. This new book is faithful in every way to the original IOM report. The co-investigators reviewed the manuscript in detail. Symptoms if not diseases can be relieved, but for most patients there are more effective approved medicines today. On the other hand, the basic science suggests potential benefits of certain cannabinoids, delivered without the hazards of smoking, in combination with other drugs using different receptor systems in the brain. The report recommends continued research to elaborate that potentials and thorough epidemiological studies to define suspected risks such as lung cancer from smoking marijuana. Review of the science behind marijuana and cannabinoid convinces us that the often emotional debate so far has been miscast. Medical use of potent, controlled psychoactive drugs has not led to their abuse. Rather than focusing on drug control policy, the medical marijuana debate should really be about the promise of future drug development. We hope this book will further such understanding. John A. Benson, Jr., M.D. Stanley J. Watson, Jr., M.D., Ph.D.

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MARIJUANA AS MEDICINE?: The Science Beyond the Controversy MARIJUANA AS MEDICINE?

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