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of Sciences. All rights reserved.
 Marijuana
as Medicine?
The Science Beyond the Controversy

Alison Mack
Janet Joy
for the Institute of Medicine

NATIONAL ACADEMY PRESS

Washington, D.C.

of Sciences. All rights reserved.

 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 ex-
pressed 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, Mari-
juana 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.

of Sciences. All rights reserved.

 INSTITUTE OF MEDICINE
Shaping the Future for Health

of Sciences. All rights reserved.

 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 re-
search, 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 ad-
vise 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 na-
tional needs, encourages education and research, and recognizes the supe-
rior achievements of engineers. Dr. William A. Wulf is president of the Na-
tional 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 profes-
sions 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 medi-
cal 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 fed-
eral government. Functioning in accordance with general policies deter-
mined by the Academy, the Council has become the principal operating
agency of both the National Academy of Sciences and the National Acad-
emy 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.

of Sciences. All rights reserved.

 Acknowledgments

O
ur chief debt as authors of this book is to its predeces-
sor: the 1999 Institute of Medicine report, Marijuana and
Medicine: Assessing the Science Base. Because this land-
mark 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 ex-
perts contributed supplemental information and answered ques-
tions 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 medi-
cal 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 pro-
vided prompt, detailed, and thoughtful answers to our questions
regarding cannabis buyer’s clubs.

of Sciences. All rights reserved.

 vi ACKNOWLEDGMENTS

This book relies on the original Institute of Medicine report,

which was very much a team effort, and we continue to be in-
debted 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 Direc-
tor at the time, and Stephen Mautner, Executive Editor of the Na-
tional Academy Press. We thank them for their sustained sup-
port 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 cho-
sen for their diverse perspectives and technical expertise, in ac-
cordance with procedures approved by the National Research
Council’s Report Review Committee. The purpose of this inde-
pendent 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 stan-
dards 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 Univer-
sity, Ithaca, New York; John A. Benson, Jr., Oregon Health Sci-
ences 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 construc-
tive comments and suggestions, it must be emphasized that re-
sponsibility 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 compli-
cations of pregnancy and its joyous, but chaotic, aftermath. They
include the high-risk maternity and NICU nursing staff at

of Sciences. All rights reserved.

 ACKNOWLEDGMENTS vii

Christiana Hospital and her “extended family” at Wilmington

Montessori School. Janet Joy inspired me with her scientific ex-
pertise 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, Princi-
pal 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

of Sciences. All rights reserved.

of Sciences. All rights reserved.
 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
ix

of Sciences. All rights reserved.

of Sciences. All rights reserved.
 Preface

I
n 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 ap-
proved the medical use of marijuana. These state ballot initia-
tives, and the wider discussion they spawned about appropriate
national policies regulating marijuana, have been sharply divi-
sive. 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 sub-
terfuge 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 Con-
trol Policy (ONDCP) asked the Institute of Medicine (IOM) to re-
view the evidence for the potential benefits and risks associated
with the use of marijuana. The IOM is a non-governmental, apo-
litical, non-profit organization of scientists whose independence
and objectivity lend credibility to its studies and recommenda-
tions. The report of the 18-month IOM study was first released to
both the ONDCP and the public in March 1999.

xi

of Sciences. All rights reserved.

 xii PREFACE

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, pharmacol-
ogy, 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 con-
sensus about the fast-moving science that suggests the potential
of cannabinoid drugs for medical use. There are far less convinc-
ing 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 can-
nabinoids, delivered without the hazards of smoking, in combi-
nation 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 con-
vinces 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.

of Sciences. All rights reserved.

 Marijuana
as Medicine?

of Sciences. All rights reserved.

of Sciences. All rights reserved.
 I
Marijuana, Medicine,
and Science

of Sciences. All rights reserved.

of Sciences. All rights reserved.
 1
Introduction

T
here are many reasons for wanting to understand what
science has so far revealed—and what remains un-
known—about marijuana’s medical potential. Can mari-
juana really help people with AIDS (acquired immune deficiency
syndrome), cancer, glaucoma, multiple sclerosis, or any of several
other conditions it is purported to relieve? How does marijuana
affect the human body? Could the potential benefits of legalizing
marijuana for medicinal use possibly outweigh the risk of encour-
aging drug abuse? All of these questions remain to be answered
completely, but over the past two decades scientists have made
significant progress in revealing how chemicals in marijuana act
on the body. Researchers have also studied how marijuana use
affects individuals and society as a whole.
Unfortunately, much of what scientists have learned about
the medical use of marijuana has been obscured by highly polar-
ized debate over the drug’s legal status. At times advocates for
medical marijuana have appeared to be discussing a different
drug than their opponents. Consider the following statements:
There are over ten thousand documented studies available that con-
firm the harmful physical and psychological effects of . . . mari-
juana.
—from the California Narcotic Officers’ Association
Marijuana is NOT a Medicine, Santa Clarita, CA (1996), p. 2.

of Sciences. All rights reserved.

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