Marijuana and
Medicine
Assessing the Science Base
EXECUTIVE
SUMMARY
Full Text of Report
Interview with the Authors (Real
Video)
Statements
of the Principal Investigators
Janet E. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr.,
Editors
Division of Neuroscience and Behavioral Health
INSTITUTE OF MEDICINE
National Academy of
Science
Washington, D.C. 1999
Notice | Principal
Investigators and Advisors | Reviewers | Preface Acknowledgments | Contents | Executive
Summary
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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
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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.
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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
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, 1998)
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
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 disciplines¾
neuroscience, pharmacology, immunology, drug abuse, drug laws, and a variety of medical
specialties including neurology, oncology, infectious diseases, and ophthalmology¾
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 study¾
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.
Contents
EXECUTIVE SUMMARY
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 patients¾
particularly older patients with no previous marijuana experience¾
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
marijuana¾
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.
STATEMENT OF TASK
The study will assess what is currently known, and not known about the
medical use of marijuana. It will include a review of the science base regarding the mechanism of
action of marijuana, an examination of the peer-reviewed scientific literature on the efficacy of
therapeutic uses of marijuana, and the costs of using various forms of marijuana versus approved
drugs for specific medical conditions (e.g., glaucoma, multiple sclerosis, wasting diseases, nausea,
and pain).
The study will also include an evaluation of the acute and chronic
effects of marijuana on health and behavior; a consideration of the adverse effects of marijuana
use compared with approved drugs; an evaluation of the efficacy of different delivery systems for
marijuana (e.g., inhalation vs. oral); and an analysis of the data concerning marijuana as a gateway
drug; and an examination of the possible differences in the effects of marijuana due to age and
type of medical condition.
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
effects
Therapeutic 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
These specific areas, along with the assessments described above will be
integrated into a broad description and assessment of the available literature relevant to the
medical use of marijuana. |
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. |
Scientific data indicate the potential
therapeutic value of cannabinoid drugs for pain relief, control of nausea and vomiting, and
appetite stimulation. This value would be enhanced by a rapid onset of drug
effect. |
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. |
The psychological effects of
cannabinoids are probably important determinants of their potential therapeutic value. They can
influence symptoms indirectly which could create false impressions of the drug effect or be
beneficial as a form of adjunctive therapy. |
Recommendation 3: Psychological
effects of cannabinoids such as anxiety reduction and sedation, which can influence perceived
medical benefits, should be evaluated in clinical trials. |
Numerous studies suggest that
marijuana smoke is an important risk factor in the development of respiratory diseases, but the
data that could conclusively establish or refute this suspected link have not been
collected. |
Recommendation 4: Studies to
define the individual health risks of smoking marijuana should be conducted, particularly among
populations in which marijuana use is prevalent. |
Because marijuana is a crude THC
delivery system that also delivers harmful substances, smoked marijuana should generally not be
recommended for medical use. Nonetheless, marijuana is widely used by certain patient groups,
which raises both safety and efficacy issues. |
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. |
If there is any future for marijuana as a
medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives.
Isolated cannabinoids will provide more reliable effects than crude plant mixtures. Therefore, the
purpose of clinical trials of smoked marijuana would not be to develop marijuana as a licensed
drug, but such trials could be a first step towards the development of rapid-onset, nonsmoked
cannabinoid delivery systems. |
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.
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