Copyright 1999 by the National Academy of Sciences. All rights
reserved.
The serpent has been a symbol of long life, healing, and
knowledge among almost all cultures and religions since the beginning
of recorded history. The image adopted as a logotype by the Institute
of Medicine is based on a relief carving from ancient Greece,
now held by the Staatliche Museum in Berlin.
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
iii
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
iv
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.
v
Preface
Why study the medical value of marijuana now? What circumstances
provoked this analysis and report? There have been a variety of
influences since the IOM Report of 1982. First, advocates of personal
choice with a growing distrust of scientific medicine sought alternatives
congruent with their values about health and life. This view was
expressed at the ballot box in recent state referenda. Proponents
claimed their own "scientific evidence" of marijuana's
safety and effectiveness. Others, distressed by the societal ravages
of drug abuse, especially among young people, view legalized medical
marijuana as a subterfuge enabling liberalization, the potential
"gateway" to even more harmful substance abuse. Meanwhile,
there have been remarkable and accelerating advances of relevant
knowledge in molecular and behavioral neuroscience, in particular
newly elaborated systems of transmitters, receptors, and antagonists
all illuminating the physiological effects of cannabinoids, both
those found in nature and those normally found in the brain. (Cannabinoids
are the group of compounds related to THC, the primary psychoactive
ingredient in marijuana.) The new science could inform policies
responding to the public divide.
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.
Information for this study was gathered through analysis
of the relevant scientific literature, scientific workshops, site
visits to cannabis buyers' clubs and HIV/AIDS clinics, and extensive
consultation with biomedical and social scientists. Three 2-day
workshops -- in Irvine, California; New Orleans, Louisiana; and
Washington, DC -- were open to the public and included scientific
presentations and also 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. 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
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.
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,
nausea, 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.
John A. Benson, Jr., M.D.
Stanley J. Watson, Jr. M.D., Ph.D.
Principal Investigators
Acknowledgments
This report covers such a broad range of disciplines --
neuroscience, pharmacology, immunology, drug abuse, drug laws,
and a variety of medical specialties including neurology, oncology,
infectious diseases, and ophthalmology -- 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 study -- 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 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
ES.1
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.
ES.2
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
(Valium®).
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
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.
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
The psychological effects of THC and similar cannabinoids
pose three issues for the therapeutic use of cannabinoid drugs.
First, for some patients -- particularly older patients with no
previous marijuana experience -- 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.
ES.5
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.
ES.6
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 marijuana -- 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.
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
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.
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.
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 e-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.
ES.9
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 palm).
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.
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
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.
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.
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
y 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.
ES.12
Chapter 1 --->>>
