PREPUBLICATION COPY
UNCORRECTED PROOFS
MARIJUANA AND MEDICINE:
ASSESSING THE SCIENCE BASE
INSTITUTE OF MEDICINE
MARIJUANA AND MEDICINE:
ASSESSING THE SCIENCE BASE
Janet E. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr., Editors
Division of Neuroscience and Behavioral Health
INSTITUTE OF MEDICINE
NATIONAL ACADEMY PRESS
Washington, D.C. 1999
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 report were chosen for their special competences and with regard for appropriate balance.
Copyright 1999 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
Principal Investigators and Advisory Panel
JOHN A. BENSON, JR., co-Principal Investigator, Dean and Professor of Medicine, Emeritus, Oregon Health Sciences University School of Medicine, Portland, Oregon
STANLEY J. WATSON, JR., co-Principal Investigator, co-Director and Research Scientist, Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan
STEVEN R. CHILDERS, Professor, Bowman Gray School of Medicine, Wake Forest University, Center for Neuroscience, Winston-Salem, North Carolina
J. RICHARD CROUT, Private Consultant, Bethesda, Maryland
THOMAS J. CROWLEY, Professor, University of Colorado, Health Sciences Center, Addiction Research and Treatments Services, Denver, Colorado
JUDITH FEINBERG, Professor, University of Cincinnati Medical Center, Division of Infectious Diseases, Department of Internal Medicine, Cincinnati, Ohio
HOWARD L. FIELDS, Professor, University of California in San Francisco, Neurology and Anesthesiology, San Francisco, California
DOROTHY HATSUKAMI, Professor, University of Minnesota, Department of Psychiatry,
Minneapolis, Minnesota
ERIC B. LARSON, Medical Director, University of Washington Medical Center, Seattle, Washington
BILLY R. MARTIN, Professor, Virginia Commonwealth University, Department of Pharmacology, Richmond, Virginia
TIMOTHY VOLLMER, Professor, Yale School of Medicine, Yale MS Research Center, New Haven, Connecticut
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Study Staff
JANET E. JOY, Study Director
DEBORAH O. YARNELL, Research Associate
AMELIA B. MATHIS, Project Assistant
CHERYL MITCHELL, Administrative Assistant (until September, 1998)
THOMAS J. WETTERHAN, Research Assistant (until September, 1988)
CONSTANCE M. PECHURA, Division Director (until April 1998)
NORMAN GROSSBLATT, Manuscript Editor
Consultant
MIRIAM DAVIS
Section Staff
CHARLES H. EVANS, JR., Head, Health Sciences Section
LINDA DEPUGH, Administrative Assistant
CARLOS GABRIEL, Financial Associate
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REVIEWERS
JAMES ANTHONY,
Johns Hopkins University
JACK BARCHAS, Cornell University Medical College
SUMNER BURSTEIN, University of Massachusetts Medical School
AVRAM GOLDSTEIN, Stanford University
LESTER GRINSPOON, Harvard Medical School
MILES HERKENHAM, National Institute of Mental Health, National Institutes of Health
HERBERT KLEBER, Columbia University
GEOFFREY LEVITT, Venable Attorneys at Law
KENNETH MACKIE, University of Washington
RAPHAEL MECHOULAM, Hebrew University
CHARLES O'BRIEN, University of Pennsylvania
JUDITH RABKIN, Columbia University
ERIC VOTH, International Drug Strategy Institute
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Preface
comments from November 1997 until November 1998. Some 130 organizations were invited to participate in the public workshops. Many people in the organizations --particularly those opposed to the medical use of marijuana -- felt that a public forum was not conducive to expressing their views; they were invited to communicate their opinions (and reasons for holding them) by mail or telephone. As a result, roughly equal numbers of persons and organizations opposed to and in favor of the medical use of marijuana were heard from.
John A. Benson, Jr., M.D.
Stanley J. Watson, Jr. M.D., Ph.D.
Principal Investigators
Acknowledgments
the San Francisco Cannabis Cultivators Club, Scott Imler staff at the Los Angeles Cannabis Resource Center, Victor Hernandez and members of Californians Helping Alleviate Medical Problems (CHAMPS), Michael Weinstein of the AIDS Health Care Foundation, and Marsha Bennett of the Louisiana State University Medical Center.
EXECUTIVE SUMMARY
EXECUTIVE SUMMARY | 2 |
EFFECTS OF ISOLATED CANNABINOIDS | 3 |
RISKS ASSOCIATED WITH MEDICAL USE OF MARIJUANA | 6 |
USE OF SMOKED MARIJUANA | 8 |
ES.1
EXECUTIVE SUMMARY
ES.2
*Evaluation of the effects of isolated cannabinoids.
*Evaluation of the health risks associated with the medical use of marijuana.
*Evaluation of the efficacy of marijuana.
EFFECTS OF ISOLATED CANNABINOIDS
Cannabinoid Biology
CONCLUSION: At this point, our knowledge about the biology of marijuana and cannabinoids allows us to make some general conclusions:
*Cannabinoids likely have a natural role in pain modulation, control of movement, and memory.
*The natural role of cannabinoids in immune systems is likely multifaceted and remains unclear.
*The brain develops tolerance to cannabinoids.
*Animal research demonstrates the potential for dependence, but this potential is observed under a narrower range of conditions than with benzodiazepines, opiates, cocaine, or nicotine.
*Withdrawal symptoms can be observed in animals, but appear to be mild compared to opiates or benzodiazepines, such as diazepam (ValiumŪ).
ES.3
CONCLUSION: The different cannabinoid receptor types found in the body appear to play different roles in normal human physiology. In addition, some effects of cannabinoids appear to be independent of those receptors. The variety of mechanisms through which cannabinoids can influence human physiology underlies the variety of potential therapeutic uses for drugs that might act selectively on different cannabinoid systems.RECOMMENDATION 1: Research should continue into the physiological effects of synthetic and plant-derived cannabinoids and the natural function of cannabinoids found in the body. Because different cannabinoids appear to have different effects, cannabinoid research should include, but not be restricted to, effects attributable to THC alone.
Efficacy Of Cannabinoid Drugs
ES.4
CONCLUSION: Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation; smoked marijuana, however, is a crude THC delivery system that also delivers harmful substances.
RECOMMENDATION 2: Clinical trials of cannabinoid drugs for symptom management should be conducted with the goal of developing rapid-onset, reliable, and safe delivery systems.
Influence Of Psychological Effects On Therapeutic Effects
CONCLUSION: The psychological effects of cannabinoids, such as anxiety reduction, sedation, and euphoria can influence their potential therapeutic value Those effects are potentially undesirable for certain patients and situations, and beneficial for others. In addition, psychological effects can complicate the interpretation of other aspects of the drug effect.
RECOMMENDATION 3: Psychological effects of cannabinoids such as anxiety reduction and sedation, which can influence medical benefits, should be evaluated in clinical trials.
ES.5
RISKS ASSOCIATED WITH MEDICAL USE OF MARIJUANA
Physiological Risks
CONCLUSION: Numerous studies suggest that marijuana smoke is an important risk factor in the development of respiratory disease.
RECOMMENDATION 4: Studies to define the individual health risks of smoking marijuana should be conducted, particularly among populations in which marijuana use is prevalent.
ES.6
Marijuana Dependence And Withdrawal
CONCLUSION: A distinctive marijuana withdrawal syndrome has been identified, but it is mild and short-lived. The syndrome includes restlessness, irritability, mild agitation, insomnia, sleep EEG disturbance, nausea, and cramping.
Marijuana As A "Gateway" Drug
ES.7
CONCLUSION: Present data on drug use progression neither support nor refute the suggestion that medical availability would increase drug abuse. However, this question is beyond the issues normally considered for medical uses of drugs, and should not be a factor in evaluating the therapeutic potential of marijuana or cannabinoids.
USE OF SMOKED MARIJUANA
RECOMMENDATION 5: Clinical trials of marijuana use for medical purposes should be conducted under the following limited circumstances: trials should involve only short-term marijuana use (less than six months); be conducted in patients with conditions for which there is reasonable expectation of efficacy; be approved by institutional review boards; and collect data about efficacy.
ES.8
RECOMMENDATION 6: Short-term use of smoked marijuana (less than six months) for patients with debilitating symptoms (such as intractable pain or vomiting) must meet the following conditions:
*failure of all approved medications to provide relief has been documented;
*the symptoms can reasonably be expected to be relieved by rapid onset cannabinoid drugs;
*such treatment is administered under medical supervision in a manner that allows for assessment of treatment effectiveness;
*and involves an oversight strategy comparable to an institutional review board process that could provide guidance within 24 hours of a submission by a physician to provide marijuana to a patient for a specified use.
ES.9
Statement of Task
Specific Issues
Specific issues to be addressed fall under three broad categories: the science base, therapeutic use, and economics.
Science Base
*Review of neuroscience related to marijuana, particularly relevance of new studies on addiction and craving
*Review of behavioral and social science base of marijuana use, particularly assessment of the relative risk of progression to other drugs following marijuana use
*Review of the literature determining which chemical components of crude marijuana are responsible of possible therapeutic effects and for side effectsTherapeutic Use
*Evaluation of any conclusions on the medical use of marijuana drawn by other groups
*Efficacy and side-effects of various delivery systems for marijuana compared to existing medications for glaucoma, wasting syndrome, pain, nausea, or other symptoms
*Differential effects of various forms of marijuana that relate to age or type of disease.Economics
*Costs of various forms of marijuana compared with costs of existing medications for glaucoma, wasting syndrome, pain, nausea, or other symptoms
*Assessment of differences between marijuana and existing medications in terms of access and availability
ES.10
Recommendations
Recommendation 1: Research should continue into the physiological effects of synthetic and plant-derived cannabinoids and the natural function of cannabinoids found in the body. Because different cannabinoids appear to have different effects, cannabinoid research should include, but not be restricted to effects attributable to THC alone
Recommendation 2: Clinical trials of cannabinoid drugs for symptom management should be conducted with the goal of developing rapid-onset, reliable, and safe delivery systems.
Recommendation 3: Psychological effects of cannabinoids such as anxiety reduction and sedation, which can influence perceived medical benefits, should be evaluated in clinical trials.
ES.11
Recommendation 4: Studies to define the individual health risks of smoking marijuana should be conducted, particularly among populations in which marijuana use is prevalent.
Recommendation 5: Clinical trials of marijuana use for medical purposes should be conducted under the following limited circumstances: trials should involve only short-term marijuana use (less than six months); be conducted in patients with conditions for which there is reasonable expectation of efficacy; be approved y institutional review boards; and collect data about efficacy.
Recommendation 6: Short term use of smoked marijuana (less than six months) for patients with debilitating symptoms (such as intractable pain or vomiting) must meet the following conditions:
*failure of all approved medications to provide relief has been documented;
*the symptoms can reasonably be expected to be relieved by rapid-onset cannabinoid drugs;
*such treatment is administered under medical supervision in a manner that allows for assessment of treatment effectiveness;
*and involves an oversight strategy comparable to an institutional review board process that could provide guidance within 24 hours of a submission by a physician to provide marijuana to a patient for a specified use.
ES.12