Executive Summary, Marijuana And Medicine

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Source: Institute of Medicine
Copyright: 1999 by the National Academy of Sciences
Pubdate: Wed, 17 Mar 1999
Websites: See below

EXECUTIVE SUMMARY, 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, 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.

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 both 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.

This study was supported under contract No. DC7C02 from the Executive
Office of the President, Office of the National Drug Control Policy.

This Executive Summary is available in limited quantities from the
Institute of Medicine, Division of Neuroscience and Behavioral Health, 2101
Constitution Avenue, N.W., Washington, DC 20418. The full text is available
on line at: www.nap.edu. 

The complete volume of Marijauna and Medicine: Assessing the Science Base
is available for sale from the National Academy Press, 2101 Constitution
Avenue, N.W., Lock Box 285, Washington, DC 20055. Call (800) 624-6242 or
(202) 334-3313 (in the Washington metropolitan area), or visit the NAP's
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The full text of the prepublication version of this report is available on
line at
http://www.nap.edu/readingroom/enter2.cgi?0309071550.html

For more information about the Institute of Medicine, visit the IOM home
page at http://www2.nas.edu/iom

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

REVIEWERS

This report 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 the published
report as sound as possible and to ensure that the report meets
institutional standards for objectivity, evidence, and responsiveness to
the study charge. The review comments and draft manuscript remain
confidential to protect the integrity of the deliberative process. The
committee wishes to thank the following individuals for their participation
in the review of this report:

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

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 authoring committee and the
Institute of Medicine.

PREFACE 

Public opinion on the medical value of marijuana has been sharply divided.
Some dismiss medical marijuana as a hoax that exploits our natural
compassion for the sick; others claim it is a uniquely soothing medicine
that has been withheld from patients through regulations based on false
claims. Proponents of both views cite 'scientific evidence' to support
their views and have expressed those views at the ballot box in recent
state elections. In January 1997, the White House Office of National Drug
Control Policy (ONDCP) asked the Institute of Medicine to conduct a review
of the scientific evidence to assess the potential health benefits and
risks of marijuana and its constituent cannabinoids. That review began in
August 1997 and culminates with this report.

The ONDCP request came in the wake of state "medical marijuana"
initiatives. In November 1996, voters in California and Arizona passed
referenda designed to permit the use of marijuana as medicine. Although
Arizona's referendum was invalidated five months later, the referenda
galvanized a national response. In November 1998, voters in six states
(Alaska, Arizona, Colorado, Nevada, Oregon, and Washington) passed ballot
initiatives in support of medical marijuana. (The Colorado vote will not
count, however, because after the vote was taken a court ruling determined
there had not been enough valid signatures to place the initiative on the
ballot.)

Information for this study was gathered through scientific workshops, site
visits to cannabis buyers' clubs and HIV/AIDS clinics, analysis of the
relevant scientific literature, and extensive consultation with biomedical
and social scientists. The three 2-day workshops-in Irvine, California; New
Orleans, Louisiana; and Washington, DC-were open to the public and included
scientific presentations and reports, mostly from patients and their
families, about their experiences with and perspectives on the medical use
of marijuana. Scientific experts in various fields were selected to talk
about the latest research on marijuana, cannabinoids, and related topics.
(Cannabinoids are drugs with actions similar to THC, the primary
psychoactive ingredient in marijuana.) In addition, advocates for and
against the medical use of marijuana were invited to present scientific
evidence in support of their positions. Finally, the Institute of Medicine
appointed a panel of nine experts to advise the study team on technical
issues.

Public outreach included setting up a Web site that provided information
about the study and asked for input from the public. The Web site was open
for comment 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.

Advances in cannabinoid science of the last 16 years have given rise to a
wealth of new opportunities for the development of medically useful
cannabinoid-based drugs. The accumulated data suggest a variety of
indications, particularly for pain relief, antiemesis, and appetite
stimulation. For patients, such as those with AIDS or undergoing
chemotherapy, who suffer simultaneously from severe pain, nausea, and
appetite loss, cannabinoid drugs might offer broad spectrum relief not
found in any other single medication.

Marijuana is not a completely benign substance. It is a powerful drug with
a variety of effects. However, the harmful effects to individuals from the
perspective of possible medical use of marijuana are not necessarily the
same as the harmful physical effects of drug abuse. 

Although marijuana smoke delivers THC and other cannabinoids to the body,
it also delivers harmful substances, including most of those found in
tobacco smoke. In addition, plants contain a variable mixture of
biologically-active compounds and cannot be expected to provide a precisely
defined drug effect. For those reasons, the report concludes that the
future of cannabinoid drugs lies not in smoked marijuana, but in
chemically-defined drugs that act on the cannabinoid systems that are a
natural component of human physiology. Until such drugs can be developed
and made available for medical use, the report recommends interim solutions.

Acknowledgments

This report covers such a broad range of disciplinesž neuroscience,
pharmacology, immunology, drug abuse, drug laws, and a variety of medical
specialties including neurology, oncology, infectious diseases, and
ophthalmologyž that it would not have been complete without the generous
support of many people. Our goal in preparing this report was to identify
the solid ground of scientific consensus, and steer clear of the muddy
distractions of opinions that are inconsistent with careful scientific
analysis. To this end, we consulted extensively with experts in each of the
disciplines covered in this report. We are deeply indebted to each of them.

Members of the Advisory Panel, selected because each is recognized as among
the most accomplished in their respective disciplines (see list), provided
guidance to the study team throughout the studyž from helping to lay the
intellectual framework to reviewing early drafts of the report.

The following people wrote invaluable background papers for the report:
Steven R. Childers, Paul Consroe, J. Richard Gralla, Howard Fields, Norbert
Kaminski, Paul Kaufman, Thomas Klein, Donald Kotler, Richard Musty, Clara
Sanudo-Pena, C. Robert Schuster, Stephen Sidney, Donald P.Tashkin, and J.
Michael Walker.

Others provided expert technical commentary on draft sections of the
report: Richard Bonnie, Keith Green, Frederick Fraunfelder, Andrea Hohmann,
John McAnulty, Craig Nichols, John Nutt, and Robert Pandina.

Still others responded to many inquiries, provided expert counsel, or
shared their unpublished data: Paul Consroe, Geoffrey Levitt, Richard
Musty, David Pate, Roger Pertwee, Raphael Mechoulam, Clara Sanudo-Pena,
Carl Soderstrom, J. Michael Walker, and Scott Yarnell.

Miriam Davis, consultant to the study team, provided excellent written
material for the chapter on cannabinoid drug development.

The reviewers for the report (see list) provided extensive and constructive
suggestions for improving the report. It was greatly enhanced by their
thoughtful attentions.

Many of these people assisted us through many iterations of the report. All
of them made contributions that were essential to the strength of the
report. At the same time, it must be emphasized that responsibility for the
final content of report rests entirely with the authors and the Institute
of Medicine.

We would also like to thank the people who hosted our visits to their
organizations. They were unfailingly helpful and generous with their time.
Jeffrey Jones and members of the Oakland Cannabis Buyers' Cooperative,
Denis Peron of the San Francisco Cannabis Cultivators Club, Scott Imler and
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.

We also appreciate the many people who spoke at the public workshops or
wrote to share their views on the medical use of marijuana (see Appendix AA).

Jane Sanville, project officer for the study sponsor, was consistently
helpful during the many negotiations and discussion held throughout study
process. 

Many IOM staff members provided much appreciated administrative, research,
and intellectual support during the study. Robert Cook-Deegan, Marilyn
Field, Constance Pechura, Daniel Quinn, Michael Stoto provided thoughtful
and insightful comments on draft sections of the report. Others provided
advice and consultation in many other aspects of the study process:
Kathleen Stratton, Susan Fourt, Carolyn Fulco, Carlos Gabriel, Linda
Kilroy, Catharyn Liverman, Clyde Behney, Dev Mani. As project assistant
throughout the study, Amelia Mathis was tireless, gracious, and reliable. 

Deborah Yarnell's contribution as Research Associate for this study was
outstanding. She organized site visits, researched and drafted technical
material for the report, and consulted extensively with relevant experts to
ensure the technical accuracy of the text. The quality of her contributions
throughout this study was exemplary.

Finally, the Principal Investigators on this study wish to personally thank
Janet Joy for her deep commitment to the science and shape of this report.
In addition, her help in integrating the entire data gathering and
information organization of this report were nothing short of essential.
Her knowledge of neurobiology, her sense of quality control, and her
unflagging spirit over the 18 months illuminated the subjects and were
indispensable to the study's successful completion.

EXECUTIVE SUMMARY

Effects of Isolated Cannabinoids

Risks Associated with Medical Use of Marijuana

Use of Smoked Marijuana

The contents of the entire report, from which this Executive Summary is
extracted, are listed below.

1 INTRODUCTION

2 CANNABINOIDS AND ANIMAL PHYSIOLOGY

3 FIRST, DO NO HARM: CONSEQUENCES OF MARIJUANA USE AND ABUSE

4 THE MEDICAL VALUE OF MARIJUANA AND RELATED SUBSTANCES

5 DEVELOPMENT OF CANNABINOID DRUGS

APPENDIXES

A Workshop Agendas

AA Individuals and Organizations that Spoke or Wrote to the Institute of
Medicine

B Scheduling Definitions

C Statement of Task

D Recommendations made in Recent Reports on the Medical Use of Marijuana

E Rescheduling Criteria

..........

EXECUTIVE SUMMARY

Public opinion on the medical value of marijuana has been sharply divided.
Some dismiss medical marijuana as a hoax that exploits our natural
compassion for the sick; others claim it is a uniquely soothing medicine
that has been withheld from patients through regulations based on false
claims. Proponents of both views cite "scientific evidence" to support
their views and have expressed those views at the ballot box in recent
state elections. In January 1997, the White House Office of National Drug
Control Policy (ONDCP) asked the Institute of Medicine to conduct a review
of the scientific evidence to assess the potential health benefits and
risks of marijuana and its constituent cannabinoids (see box: Statement of
Task). That review began in August 1997 and culminates with this report.

The ONDCP request came in the wake of state "medical marijuana"
initiatives. In November 1996, voters in California and Arizona passed
referenda designed to permit the use of marijuana as medicine. Although
Arizona's referendum was invalidated five months later, the referenda
galvanized a national response. In November 1998, voters in six states
(Alaska, Arizona, Colorado, Nevada, Oregon, and Washington) passed ballot
initiatives in support of medical marijuana. (The Colorado vote will not
count, however, because after the vote was taken a court ruling determined
there had not been enough valid signatures to place the initiative on the
ballot.)

Can marijuana relieve health problems? Is it safe for medical use? Those
straightforward questions are embedded in a web of social concerns, most of
which lie outside the scope of this report. Controversies concerning the
nonmedical use of marijuana spill over onto the medical marijuana debate
and obscure the real state of scientific knowledge. In contrast with the
many disagreements bearing on social issues, the study team found
substantial consensus among experts in the relevant disciplines on the
scientific evidence about potential medical uses of marijuana.

This report summarizes and analyzes what is known about the medical use of
marijuana; it emphasizes evidence-based medicine (derived from knowledge
and experience informed by rigorous scientific analysis), as opposed to
belief-based medicine (derived from judgment, intuition, and beliefs
untested by rigorous science).

Throughout this report, marijuana refers to unpurified plant substances,
including leaves or flower tops whether consumed by ingestion or smoking.
References to "the effects of marijuana" should be understood to include
the composite effects of its various components; that is, the effects of
THC, the primary psychoactive ingredient in marijuana, are included among
its effects, but not all the effects of marijuana are necessarily due to
THC. Cannabinoids are the group of compounds related to THC, whether found
in the marijuana plant, in animals, or synthesized in chemistry laboratories.

Three focal concerns in evaluating the medical use of marijuana are:

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

Much has been learned since a 1982 IOM Marijuana and Health report.
Although it was clear then that most of the effects of marijuana were due
to its actions on the brain, there was little information about how THC
acted on brain cells (neurons), which cells were affected by THC, or even
what general areas of the brain were most affected by THC. Additionally,
too little was known about cannabinoid physiology to offer any scientific
insights into the harmful or therapeutic effects of marijuana. That all
changed with the identification and characterization of cannabinoid
receptors in the 1980s and 1990s. During the last 16 years, science has
advanced greatly and can tell us much more about the potential medical
benefits of cannabinoids. 

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 (Valiumâ ).

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

The accumulated data indicate a potential therapeutic value for cannabinoid
drugs, particularly for symptoms such as pain relief, control of nausea and
vomiting, and appetite stimulation. The therapeutic effects of cannabinoids
are best established for THC, which is generally one of the two most
abundant of the cannabinoids in marijuana. (Cannabidiol, the precursor of
THC, is generally the other most abundant cannabinoid.) 

The effects of cannabinoids on the symptoms studied are generally modest,
and in most cases, there are more effective medications. However, people
vary in their responses to medications and there will likely always be a
subpopulation of patients who do not respond well to other medications. The
combination of cannabinoid drug effects (anxiety reduction, appetite
stimulation, nausea reduction, and pain relief) suggests that cannabinoids
would be moderately well suited for certain conditions, such as
chemotherapy-induced nausea and vomiting and AIDS wasting.

Defined substances, such as purified cannabinoid compounds, are preferable
to plant products which are of variable and uncertain composition. Use of
defined cannabinoids permits a more precise evaluation of their effects,
whether in combination or alone. Medications that can maximize the desired
effects of cannabinoids and minimize the undesired effects can very likely
be identified.

Although most scientists who study cannabinoids agree that the pathways to
cannabinoid drug development are clearly marked, there is no guarantee that
the fruits of scientific research will be made available to the public for
medical use. Cannabinoid-based drugs will only become available if public
investment in cannabinoid drug research is sustained, and if there is
enough incentive for private enterprise to develop and market such drugs.

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

The psychological effects of THC and similar cannabinoids pose three issues
for the therapeutic use of cannabinoid drugs. First, for some patientsž
particularly older patients with no previous marijuana experiencež the
psychological effects are disturbing. Those patients report experiencing
unpleasant feelings and disorientation after being treated with THC,
generally more severe for oral THC than for smoked marijuana. Second, for
conditions such as movement disorders or nausea, in which anxiety
exacerbates the symptoms, the anti-anxiety effects of cannabinoid drugs can
influence symptoms indirectly. This can be beneficial or can create false
impressions of the drug effect. Third, in cases where symptoms are
multifaceted, the combination of THC effects might provide a form of
adjunctive therapy; for example, AIDS wasting patients would likely benefit
from a medication that simultaneously reduces anxiety, pain, and nausea
while stimulating appetite.

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.

RISKS ASSOCIATED WITH MEDICAL USE OF MARIJUANA

Physiological Risks

Marijuana is not a completely benign substance. It is a powerful drug with
a variety of effects. However, except for the harms associated with
smoking, the adverse effects of marijuana use are within the range of
effects tolerated for other medications. The harmful effects to individuals
from the perspective of possible medical use of marijuana are not
necessarily the same as the harmful physical effects of drug abuse. When
interpreting studies purporting to show the harmful effects of marijuana,
it is important to keep in mind that the majority of those studies are
based on smoked marijuana, and cannabinoid effects cannot be separated from
the effects of inhaling smoke of burning plant material and contaminants.

For most people, the primary adverse effect of acute marijuana use is
diminished psychomotor performance. It is, therefore, inadvisable to
operate any vehicle or potentially dangerous equipment while under the
influence of marijuana, THC, or any cannabinoid drug with comparable
effects. In addition, a minority of marijuana users experience dysphoria,
or unpleasant feelings. Finally, the short-term immunosuppressive effects
are not well established but, if they exist, are not likely great enough to
preclude a legitimate medical use.

The chronic effects of marijuana are of greater concern for medical use and
fall into two categories: the effects of chronic smoking, and the effects
of THC. Marijuana smoking is associated with abnormalities of cells lining
the human respiratory tract. Marijuana smoke, like tobacco smoke, is
associated with increased risk of cancer, lung damage, and poor pregnancy
outcomes. Although cellular, genetic, and human studies all suggest that
marijuana smoke is an important risk factor for the development of
respiratory cancer, proof that habitual marijuana smoking does or does not
cause cancer awaits the results of well-designed studies.

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. 

Marijuana Dependence and Withdrawal

A second concern associated with chronic marijuana use is dependence on the
psychoactive effects of THC. Although few marijuana users develop
dependence, some do. Risk factors for marijuana dependence are similar to
those for other forms of substance abuse. In particular, antisocial
personality and conduct disorders are closely associated with substance abuse.

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

Patterns in progression of drug use from adolescence to adulthood are
strikingly regular. Because it is the most widely used illicit drug,
marijuana is predictably the first illicit drug most people encounter. Not
surprisingly, most users of other illicit drugs have used marijuana first.
In fact, most drug users begin with alcohol and nicotine before marijuanaž
usually before they are of legal age. 

In the sense that marijuana use typically precedes rather than follows
initiation of other illicit drug use, it is indeed a "gateway" drug. But
because underage smoking and alcohol use typically precede marijuana use,
marijuana is not the most common, and is rarely the first, "gateway" to
illicit drug use. There is no conclusive evidence that the drug effects of
marijuana are causally linked to the subsequent abuse of other illicit
drugs. An important caution is that data on drug use progression cannot be
assumed to apply to the use of drugs for medical purposes. It does not
follow from those data that if marijuana were available by prescription for
medical use, the pattern of drug use would remain the same as seen in
illicit use.

Finally, there is a broad social concern that sanctioning the medical use
of marijuana might increase its use among the general population. At this
point there are no convincing data to support this concern. The existing
data are consistent with the idea that this would not be a problem if the
medical use of marijuana were as closely regulated as other medications
with abuse potential.

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

Because of the health risks associated with smoking, smoked marijuana
should generally not be recommended for long-term medical use. Nonetheless,
for certain patients, such as the terminally ill or those with debilitating
symptoms, the long-term risks are not of great concern. Further, despite
the legal, social, and health problems associated with smoking marijuana,
it is widely used by certain patient groups.

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.

The goal of clinical trials of smoked marijuana would not be to develop
marijuana as a licensed drug, but rather as a first step towards the
possible development of nonsmoked, rapid-onset cannabinoid delivery
systems. However, it will likely be many years before a safe and effective
cannabinoid delivery system, such as an inhaler, will be available for
patients. In the meantime, there are patients with debilitating symptoms
for whom smoked marijuana might provide relief. The use of smoked marijuana
for those patients should weigh both the expected efficacy of marijuana and
ethical issues in patient care, including providing information about the
known and suspected risks of smoked marijuana use.

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.

Until a non-smoked, rapid-onset cannabinoid drug delivery system becomes
available, we acknowledge that there is no clear alternative for people
suffering from chronic conditions that might be relieved by smoking
marijuana, such as pain or AIDS wasting. One possible approach is to treat
patients as n-of-1 clinical trials, in which patients are fully informed of
their status as experimental subjects using a harmful drug delivery system,
and in which their condition is closely monitored and documented under
medical supervision, thereby increasing the knowledge base of the risks and
benefits of marijuana use under such conditions.

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