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).
- Scientific data on controversial subjects are commonly misinterpreted, over interpreted,
and misrepresented, and the medical marijuana debate is no exception We have tried to
present the scientific studies in such a way as to reveal their strengths and limitations.
One of the goals of this report is to help people to understand the scientific data,
including the logic behind the scientific conclusions, so it goes into greater detail than
previous reports on the subject. In many cases, we have explained why particular studies
are inconclusive and what sort of evidence is needed to support particular claims about
the harms or benefits attributed to marijuana. Ideally, this report will enable the
thoughtful reader to interpret the new information about marijuana that will continue to
emerge rapidly well after this report is published.
- Can marijuana relieve health problems? Is it safe for medical use? Those straightforward
questions are embedded in a web of social concerns, which lie outside the scope of this
report. Controversies concerning non medical use of marijuana spill over onto the medical
marijuana debate and tend to obscure the real state of scientific knowledge. In contrast
with the many disagreements bearing on the social issues, the study team has found
substantial consensus, among experts in the relevant disciplines, on the scientific
evidence bearing on potential medical use.
- This report analyzes science, not the law. As in any policy debate, the value of
scientific analysis is that it can provide a foundation for further discussion. Distilling
scientific evidence does not in itself solve a policy problem. What it can do is
illuminate the common ground, bringing to light fundamental differences out of the shadows
of misunderstanding and misinformation that currently prevail. Scientific analysis cannot
be the end of the debate, but it should at least provide the basis for an honest and
informed discussion.
- Our analysis of the evidence and arguments concerning the medical use of marijuana
focuses on the strength of the supporting evidence, and does not refer to the motivations
of people who put forth the evidence and arguments. That is, it is not relevant to
scientific validity whether an argument is put forth by someone who believes that all
marijuana use should be legal or by someone who believes that any marijuana use is highly
damaging to individual users and to society as a whole. Nor does this report comment on
the degree to which scientific analysis is compatible with current regulatory policy.
Although many have argued that current drug laws pertaining to marijuana are inconsistent
with scientific data, it is important to understand that decisions about drug regulation
are based on a variety of moral and social considerations, as well as on medical and
scientific ones.
1.2
- Even when a drug is used only for medical purposes, value judgments affect policy
decisions concerning its medical use. For example, the magnitude of a drug's expected
medical benefit affects regulatory judgments about the acceptability of risks associated
with its use. Also, although a drug is normally approved for medical use only on proof of
its "safety and efficacy," patients with life-threatening conditions are
sometimes (under protocols for "compassionate use") allowed access to unapproved
drugs whose benefits and risks are uncertain. Value judgments play an even more
substantial role in regulatory decisions concerning drugs, such as marijuana, that are
sought and used for non medical purposes. Then policy-makers must take into account not
only the risks and benefits associated with medical use, but also possible interactions
between the regulatory arrangements governing medical use and the integrity of the legal
controls set up to restrict non medical use.
- It should be clear that many elements of drug control policy lie outside the realm of
biology and medicine. Ultimately, the complex moral and social judgments that underlie
drug control policy must be made by the American people and their elected officials A goal
of this report is to evaluate the biological and medical factors that should be taken into
account in making those judgments.
How This Study Was Conducted
- Information was gathered through scientific workshops, site visits, 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
(listed in appendix A). The selection of the experts was based on recommendations by their
peers, who ranked them among the most accomplished scientists and the most knowledgeable
about marijuana and cannabinoids in their own fields. In addition, advocates for (John
Morgan) and against (Eric A. Voth) the medical use of marijuana were invited to present
scientific evidence in support of their positions.
- Information presented at the scientific workshops was supplemented by analysis of the
scientific literature, and evaluating the methods used in various studies and the validity
of the authors' conclusions. Different kinds of clinical studies are useful in different
ways: results of a controlled, double-blind study with adequate sample sizes can be
expected to apply to the general population from which study subjects were drawn; an
isolated case report can suggest further studies, but cannot be presumed to be broadly
applicable; and survey data can be highly informative, but are generally limited by the
need to rely on self-reports of drug use and on unconfirmed medical diagnoses. This report
relies mainly on the most
1.3
relevant and methodologically rigorous studies available, and treats the results of
more limited studies cautiously. In addition, study results are presented in such a way as
to allow thoughtful readers to judge the results themselves.
- IOM appointed a panel of nine experts to advise the study team on technical issues.
These included neurology and the treatment of pain (Howard Fields), regulation of
prescription drugs (J. Richard Crout), AIDS wasting and clinical trials (Judith Feinberg),
treatment and pathology of multiple sclerosis (Timothy Vollmer), drug dependence among
adolescents (Thomas Crowley), varieties of drug dependence (Dorothy Hatsukami), internal
medicine, health care delivery, and clinical epidemiology (Eric B. Larson), cannabinoids
and marijuana pharmacology (Billy R. Martin), and cannabinoid neuroscience (Steven R.
Childers).
- 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.
- The study team visited four cannabis buyers' clubs in California (the Oakland Cannabis
Buyers' Cooperative, the San Francisco Cannabis Cultivators Club, the Los Angeles Cannabis
Resource Center, and Californians Helping Alleviate Medical Problems, or CHAMPS) and two
HIV-AIDS clinics (the AIDS Health Care Foundation in Los Angeles and the Louisiana State
University Medical Center in New Orleans). We listened to many individual stories from the
buyers' clubs about using marijuana to treat a variety of symptoms and heard clinical
observations on the use of MarinolŪ to treat AIDS patients. MarinolŪ is the brand name
for dronabinol, which is
9-tetrahydrocannabinol
(THC) in pill form and is available by prescription for the treatment of nausea associated
with chemotherapy and AIDS wasting. 1.4
Marijuana, Today
The Changing Legal Landscape
- In the 20th century, marijuana has been used more for its euphoric effects than as a
medicine. Its psychological and behavioral effects have concerned public officials since
the drug first appeared in the southwestern and southern states during the first two
decades of the century. By 1931, at least 29 states had prohibited use of the drug for non
medical purposes.3 Marijuana was first regulated at the federal level by the
Marijuana Tax Act of 1937, which required anyone producing, distributing, or using
marijuana for medical purposes to register and pay a tax, and which effectively prohibited
non medical use of the drug. Although the Act did not make medical use of marijuana
illegal, it did make it expensive and inconvenient. In 1942, marijuana was removed from
the U.S. Pharmacopoeia because it was believed to be a harmful and addictive drug that
caused psychoses, mental deterioration, and violent behavior.
- In the late 1960s and early 1970s, there was a sharp increase in marijuana use among
adolescents and young adults. The current legal status of marijuana was established in
1970 with the passage of the Controlled Substances Act, which divided drugs into five
Schedules and placed marijuana in Schedule I, the category for drugs with high potential
for abuse and no accepted medical use (see appendix B. scheduling criteria). In 1972, the
National Organization for the Reform of Marijuana Legislation (NORML), an organization
which supports decriminalization of marijuana, unsuccessfully petitioned the Bureau of
Narcotics and Dangerous Drugs to move marijuana from Schedule I to Schedule II. NORML
argued that marijuana is therapeutic in numerous serious ailments, is less toxic, and in
many cases more effective than conventional medicines.13 Thus, for 25 years,
the medical marijuana movement has been closely linked with the
marijuana-decriminalization movement, which has colored the debate. Many people criticized
that association in their letters to IOM and during the public workshops of this study.
The argument against the medical use of marijuana presented most often to the IOM study
team is that "the medical marijuana movement is a Trojan horse"; that is, it is
a deceptive tactic used by advocates of marijuana decriminalization who would exploit the
public's sympathy for seriously ill patients.
- Since NORML's petition in 1972, there have been a variety of legal decisions concerning
marijuana. From 1973 to 1978, eleven states adopted statutes that decriminalized use of
marijuana, although some of them recriminalized marijuana use in the 1980s and 1990s.
During the 1970s, reports of the medical value of marijuana began to appear, particularly
claims that marijuana relieved the nausea associated with chemotherapy. Health departments
in six states conducted small studies to investigate the reports. When the AIDS epidemic
spread in the 1980s, patients found that marijuana sometimes relieved their symptoms, most
dramatically those associated with AIDS wasting. Over this period, a number of defendants
1.5
charged with unlawful possession of marijuana claimed that they were using the drug to
treat medical conditions and that violation of the law was therefore justified (the
so-called "medical necessity" defense). Although most courts rejected these
claims, some accepted them.8
- Against that backdrop, voters in California and Arizona in 1996 passed two referendums
that attempted to legalize the medical use of marijuana under particular conditions.
Public support for patient access to marijuana for medical use appears substantial; public
opinion polls taken during 1997 and 1998 generally report 60-70 percent of respondents in
favor of allowing medical uses of marijuana.15 However, those referendums are
at odds with federal laws regulating marijuana, and their implementation raises complex
legal questions.
- Despite the current level of interest, referendums and public discussions have not been
well informed by carefully reasoned scientific debate. Although previous reports have all
called for more research, the nature of the research that will be most helpful depends
greatly on the specific health conditions to be addressed. And while there have been
important recent advances in our understanding of the physiological effects of marijuana,
few of the recent investigators have had the time or resources to permit detailed
analysis. The results those advances, only now beginning to be explored, have significant
implications for the medical marijuana debate.
- Several months after the passage of the California and Arizona medical marijuana
referendums, the Office of National Drug Control Policy (ONDCP) asked whether IOM would
conduct a scientific review of the medical value of marijuana and its constituent
compounds. In August 1997, IOM formally began the study and appointed John A. Benson Jr.
and Stanley J. Watson Jr. to serve as principle investigators for the study. The charge to
IOM was to review the medical use of marijuana and the harms and benefits attributed to it
(details are given in appendix C).
1.6
Medical Marijuana Legislation Among the States
- The 1996 California referendum known as Proposition 215 allowed seriously ill
Californians to obtain and use marijuana for medical purposes without criminal prosecution
or sanction. A physician's recommendation is needed. Under the law, physicians cannot be
punished or denied any right or privilege for recommending marijuana to patients who
suffer from any illness for which marijuana will provide relief.
- The 1996 Arizona referendum known as Proposition 200 was largely about prison reform but
also gave physicians the option to prescribe controlled substances, including those in
Schedule I (e.g., marijuana), to treat the disease or relieve the suffering of seriously
or terminally ill patients. Five months after the referendum was passed, it was stalled
when Arizona legislators voted that all prescription medications must be approved by the
Food and Drug Administration, and marijuana is not so approved. In November 1998, Arizona
voters passed a second referendum designed to allow physician's to prescribe marijuana as
medicine, but this is still at odds with federal law.8 .
- As of summer 1998, eight states -- California,, Connecticut, Louisiana, New Hampshire,
Ohio, Vermont, Virginia, and Wisconsin -- had laws that permit physicians to prescribe
marijuana for medical purposes or to allow a medical necessity defense.8 In
November 1998, five states -- Arizona, Alaska, Oregon, Nevada, and Washington -- passed
medical marijuana ballot initiatives. The District of Columbia also voted on a medical
marijuana initiative, but was barred from counting the votes because an amendment designed
to prohibit them from doing so was added to the federal appropriations bill, however, exit
polls suggested that a majority of voters had approved the measure.
1.7
Marijuana and Medicine
- Marijuana plants have been used since antiquity for both herbal medication and
intoxication. The current debate over the medical use of marijuana is essentially a debate
over the value of its medicinal properties relative to the risk posed by its use.
- Marijuana's use as an herbal remedy before the 20th century is well documented.1,
10, 11 However, modern medicine adheres to different standards from those used in
the past. The question is not whether marijuana can be used as an herbal remedy, but
rather how this remedy meets today's standards of efficacy and safety. We understand much
more than previous generations about medical risks. Our society generally expects its
licensed medications to be safe, reliable, and of proven efficacy, and contaminants and
inconsistent ingredients in our health treatments are not tolerated. That refers not only
to prescription and over-the-counter drugs, but also to the vitamin supplements and herbal
remedies purchased at the grocery store. For example, the essential amino acid l-tryptophan
was widely sold in health food stores as a natural remedy for insomnia until early 1990
when it became linked to an epidemic of a new and potentially fatal illness
(eosinophilia-myalgia syndrome).9, 12 When it was removed from the market
shortly thereafter, there was little protest, despite the fact that it was safe for the
vast majority of the population. The 1536 cases and 27 deaths were later traced to
contaminants in a batch produced by a single Japanese manufacturer.
- Although few herbal medicines meet today's standards, they have provided the foundation
for modern Western pharmaceuticals. Most current prescriptions have their roots either
directly or indirectly in plant remedies.7 At the same time, most current
prescriptions are synthetic compounds that are only distantly related to the natural
compounds that led to their development. Digitalis was discovered in foxglove, morphine in
poppies, and taxol in the yew tree. Even aspirin (acetylsalicylic acid) has its
counterpart in herbal medicine: for many generations, American Indians relieved headaches
by chewing the bark of the willow tree, which is rich in a related form of salicylic acid.
- Although plants continue to be valuable resources for medical advances, drug development
is likely to be less and less reliant on plants and more reliant on the tools of modern
science. Molecular biology, bioinformatics software, and DNA array-based analyses of genes
and chemistry are all beginning to yield great advances in drug discovery and development.
Until recently, drugs could only be discovered; now they can be designed. Even the
discovery process has been accelerated through the use of modern drug screening
techniques. It is increasingly possible to identify or isolate the chemical compounds in a
plant, determine which compounds are responsible for the plant's effects, and select the
most effective and safe compounds either for use as purified substances or as tools to
develop even more effective, safer, or less expensive compounds.
1.8
- Yet even as the modern pharmacological toolbox becomes more sophisticated and
biotechnology yields an ever greater abundance of therapeutic drugs, people increasingly
seek alternative, low-technology therapies.4, 5 In 1997, 46 percent of
Americans sought nontraditional medicines and spent over 27 billion unreimbursed dollars;
the total number of visits to alternative medicine practitioners appears to have exceeded
the number of visits to primary care physicians. 5, 6 Recent interest in the
medical use of marijuana coincides with this trend toward self-help and a search for
"natural" therapies. Indeed, several people who spoke at the IOM public hearings
in support of the medical use of marijuana said that they generally preferred herbal
medicines to standard pharmaceuticals. However, few alternative therapies have been
carefully and systematically tested for safety and efficacy, as is required for
FDA-approved medications.2
Who Uses Medical Marijuana?
- There have been no comprehensive surveys of the demographics and medical conditions of
medical marijuana users, but a few reports provide some indication. In each case, survey
results should be understood to reflect the situation in which they were conducted and are
not necessarily characteristic of medical marijuana users as a whole. Respondents to
surveys reported to the IOM study team were all members of "buyers' clubs,"
organizations that provide their members with marijuana, although not necessarily through
direct cash transactions. The atmosphere of the marijuana buyers' clubs ranges from that
of the comparatively formal and closely regulated Oakland Cannabis Buyers' Cooperative to
that of a "country club for the indigent," as Dennis Peron described the San
Francisco Cannabis Cultivators Club (SFCCC), which he directed.
- John Mendelson, an internist and pharmacologist at the University of California, San
Francisco (UCSF) Pain Management Center, surveyed 100 members of the SFCCC who were using
marijuana at least weekly. Most of the respondents were unemployed men in their forties.
Subjects were paid $50 to participate in the survey; this might have encouraged a greater
representation of unemployed subjects. All subjects were tested for drug use. About half
tested positive for marijuana only; the other half tested positive for drugs in addition
to marijuana (23% for cocaine and 13% for amphetamines). The predominant disorder was
AIDS, followed by roughly equal numbers of members who reported chronic pain, mood
disorders, and musculoskeletal disorders (table 1.1).
1.9
Table 1.1 Self-Reported Disorders Treated with Marijuana by Members of San Francisco
Cannabis Cultivators Club
| Disorder |
Number of Subjects |
| HIV |
60 |
| Musculoskeletal disorders and arthritis |
39 |
| Psychiatric disorders (primarily depression) |
27 |
| Neurological disorders and nonmusculoskeletal pain syndromes |
9 |
| Gastrointestinal disorders (most often nausea) |
7 |
| Other disorders glaucoma, allergies, nephrolitiasis, and the skin manifestations of
Reiter syndrome |
7 |
| Total disorders |
149 |
| Total number of respondents |
100 |
1.10
- The membership profile of the San Francisco club was similar to that of the Los Angeles
Cannabis Resource Center (LACRC), where 83% of the 739 patients were men, 45% were 36-45
years old, and 71% were HIV-positive. Table 1.2 shows a distribution of conditions
somewhat different from that in SFCCC respondents, probably because of a different
membership profile. For example, cancer is generally a disease that occurs late in life;
34 (4.7%) of LACRC members were over 55 years old; only 2% of survey respondents in the
SFCCC study were over 55 years old.
- Jeffrey Jones, executive director of the Oakland Cannabis Buyers' Cooperative, reported
that its largest group of patients is HIV-positive men in their forties. The second
largest group is patients with chronic pain.
- Among the 42 people who spoke at the public workshops or wrote to the study team, only
six identified themselves as members of marijuana buyers' clubs. Nonetheless, they
presented a similar profile: HIV - AIDS was the predominant disorder, followed by chronic
pain (table 1.3). All HIV-AIDS patients reported that marijuana relieved nausea and
vomiting and improved their appetite. About half the patients who reported using marijuana
for chronic pain also reported that it reduced nausea and vomiting.
1.11
Table 1.2 Self-Reported Disorders Treated with Marijuana by Members of Los Angeles
Cannabis Resource Center (LACRC) According to Center Staffa
| Treated Disorder |
Number of
Subjects |
Percent of
Subjects |
| HIVb |
528 |
71 |
| Cancer |
40 |
5.4 |
| Terminal cancer |
10 |
1.4 |
Mood disorders
(depression) |
4 |
.05 |
Musculosketetal
(multiple sclerosis, arthritis) |
30 |
4.1 |
| Chronic pain and back pain |
33 |
4.5 |
| Gastrointestinal |
17 |
2.3 |
Neurological disorders
(epilepsy, Tourette syndrome, brain trauma) |
7 |
0.9 |
| Seizures or migrainec |
13 |
1.8 |
| Glaucoma |
15 |
2.0 |
| Miscellaneous |
42 |
5.7 |
| Total number |
739 |
100 |
a Results are based on review of 739 individual records by LACRC staff
members. In contrast with Mendelson's survey of SFCCC (table 1.1), only the primary
disorder is indicated here. Membership in LACRC is contingent on a doctor's letter of
acknowledgment, but diagnoses are not independently confirmed.
b HIV patients use marijuana to control nausea, increase appetite (to combat
wasting), and relieve gastrointestinal distress caused by AIDS medications. These uses are
not indicated separately.
c As described by LACRC staff; some of these cases might also be
neurological disorders.
d Because of rounding error, percentages do not add up to 100.
1.12
Table 1.3 Summary of Reports to IOM Study Team by 43 Individuals
| Symptoms |
Dominant Disease |
| Anorexia, nausea, vomiting |
AIDS(7)
AIDS and cancer
Cancer
Testicular cancer
Cancer and multiple sclerosclerosis
Thyroid conditione
Migraine
Wilsons disease |
| Mood disorders |
Depression(2)
Depression and anxiety(2)
Manic depression(2)
Posttraumatic stress
Premenstrual syndrome |
| Pain |
Migraine
Injury(2)
Epilepsy and Postpolio syndrome
Trauma and epilepsy
Degenerative disk disease
Rheumatoid arthritis
Nail-patella syndrome
Reflex sympathetic dystrophy
Gulf War chemical exposure
Multiple congenital cartilaginous exostosis
Histiocytosis X
|
| Muscle Spasticity |
spasticitye
Multiple sclerosis(3)
Paralysis
Spinal cord injury
Spasmodic torticollis |
| Intraocular pressure |
Glaucoma |
| Diarrhea |
Crohn's disease |
Table 1.3. This table lists the people who reported to the IOM study team during the
public workshops, or through letters, that they use marijuana as medicine, it should not
be interpreted as a representative sample of the full spectrum of people who use marijuana
as medicine. Each dominant disease represents an individual report.
e Not specified.
1.13
Table 1.4 Primary Symptoms of 43 Individuals who Reported to IOM Study Team
| . |
Symptom Frequency |
Multiple Symptoms |
| Primary Symptom |
Number of Reportsf |
% of Total Symptoms Reported |
Number who Reported (Primary) Additional Symptoms |
% of those who reported Primary Symptoms |
| Anorexia, nausea, vomiting |
21 |
31 |
13 |
62 |
| Diarrhea |
4 |
6 |
3 |
75 |
| Intraocular pressure |
2 |
3 |
1 |
50 |
| Mood disorders |
12 |
18 |
7 |
58 |
| Muscle spasticity |
12 |
18 |
7 |
58 |
| Pain |
16 |
24 |
13 |
81 |
| Totals |
67 |
. |
44 |
66 |
f Forty-three persons reporting; 20 reported relief from more than one
symptom.
1.14
- Note that the medical conditions referred to are only those reported to the study team
or to interviewers; they cannot be assumed to represent complete or accurate diagnoses.
Michael Rowbotham, a neurologist at the UCSF Pain Management Center, noted that many pain
patients referred to that center arrive with incorrect diagnoses or with pain of unknown
origin. At that center, the patients who report medical benefit from marijuana report that
marijuana does not reduce their pain but enables them to cope with it.
- Most -- not all -- people who use marijuana to relieve medical conditions have
previously used it recreationally. An estimated 95% of the LACRC members had used
marijuana before joining the club. It is important to emphasize the absence of
comprehensive information on marijuana use before its use for medical conditions.
Frequency of prior use almost certainly depends on many factors, including membership in a
buyers' club, membership in a population sector that uses marijuana more often than others
(for example, men 20-30 years old), and the medical condition being treated with marijuana
(for example, there are probably relatively fewer recreational marijuana users among
cancer patients than among AIDS patients).
- Patients who reported their experience with marijuana at the public workshops said that
marijuana provided them with great relief from symptoms associated with disparate diseases
and ailments, including AIDS wasting, spasticity from multiple sclerosis, depression,
chronic pain, and nausea associated with chemotherapy. Their circumstances and symptoms
were varied, and the IOM study team was not in a position to make medical evaluations or
confirm diagnoses. Three representative cases presented to the IOM study team are
presented here; the stories have been edited for brevity, but each case is presented in
the patient's words and with the patient's permission.
1.15
Boxes 1.1-1.3: Selected Cases From the Public Sessions
G.S. spoke at the IOM workshop in Louisiana about his use of marijuana first to
combat AIDS wasting syndrome and later for relief from the side effects of AIDS
medications.
- Skin rashes, dry mouth, foul metallic aftertaste, numbness of the face, swelling of the
limbs, fever spikes, headaches, dizziness, anemia, clinical depression, neuropathy so
crippling that I could not type, so painful that the bed sheets felt like sandpaper,
nausea so severe that I sometimes had to leave the dinner table to vomit, and diarrhea so
unpredictable that I dared not leave the house without diapers.
- These are some of the horrors that I endured in the last 10 years during my fight for
life against the human immunodeficiency virus. But these ravages were not caused by HIV
itself, or by any of the opportunistic infections that mark the steady progression of
AIDS. Each of these nightmares was a side effect of one of the hundreds of medications I
have taken to fight one infection after another on my way to a seemingly certain early
grave.
- Had you known me three years ago, you would not recognize me now. After years of
final-stage AIDS, I had wasted to 130 lb. The purple Kaposi's sarcoma lesions were
spreading. The dark circles under my eyes told of sleepless nights and half-waking days. I
encountered passages of time marked by medication schedules, nausea, and diarrhea. I knew
that I was dying. Every reflection shimmered with death, my ghost-like pallor in the
mirror, the contained terror on the face of a bus passenger beside me, and most of all,
the resigned sadness in my mother's eyes.
- But still I was fortunate because along the way I rediscovered the ancient understanding
of marijuana's medicinal benefit. So I smoked pot. Every day. The pot calmed my stomach
against handfuls of pills. The pot made me hungry so that I could eat without a tube. The
pot eased the pain of crippling neural side effects so that I could dial the phone by
myself. The pot calmed my soul and allowed me to accept that I would probably die soon.
Because I smoked pot I lived long enough to see the development of the first truly
effective HIV therapies. I lived to gain 50 lb, regain my vigor, and celebrate my 35th
birthday. I lived to sit on the bus without frightening the passenger beside me.
- Even at this stage of my recovery, I take a handful of pills almost every day, and will
probably continue to do so for the rest of my life. While I am grateful for the lifesaving
pro/ease-inhibitor therapies, they bring with them a host of adverse reactions and
undesirable side effects. Different patients experience different reactions, of course,
but almost all patients experience some. Smoking marijuana relieves many of these side
effects.
- I am not one of the exceptional eight patients in the United States with legal
permission to smoke marijuana. Every day I risk arrest, property forfeiture, fines, and
imprisonment. But I have no choice, you see, just as I have no choice but to endure the
side effects of these toxic medications. So many patients like me are breaking the law to
enjoy relief that no other therapy provides.
- I sit here, I believe, as living proof that marijuana can have a beneficial effect in
staving off wasting. Every pound was a day. I figured that for every pound of body weight
I could maintain, that was another day that I could live in hopes that some effective
therapy would emerge.
1.16
B.D. spoke at the IOM workshop in Louisiana She is one of eight patients who are
legally allowed to smoke marijuana under a Compassionate Use Protocol She uses marijuana
to relieve nausea, muscle spasticity, and pain associated with multiple sclerosis.
- I was diagnosed with multiple sclerosis in 1988. Prior to that, I was an active person
with ballet and swimming. I now have a swimming pool, so I swim each and every day, and I
smoke marijuana. The government has given me the marijuana to smoke. Each month, I pick up
a can filled with the marijuana cigarettes rolled by the government.
- At one time, I weighed 85 lb and I now weigh 105. Twenty pounds is quite a bit to put on
I could not walk. I did not have the appetite. I use a scooter now for distance. I can get
around the house. I have a standard poodle who is kind of like an assistant dog. She is
good at it. She helps me.
- When I found out that there was a program to get marijuana from the government, I
decided that was the answer. I was not a marijuana-smoker before that. In fact, I used to
consider the people I knew who smoked the marijuana as undesirables. Now, I myself am an
undesirable.
- But it works. It takes away the backache. With multiple sclerosis, you can get spasms,
and your leg will just go straight out and you cannot stop that leg. You may have danced
all of your life and put the leg where you wanted it to be, but the MS takes that from
you. So I use the swimming pool, and that helps a lot. The kicks are much less when I have
smoked a marijuana cigarette. Since 1991, I've smoked 10 cigarettes a day. I do not take
any other drugs. Marijuana seems to have been my helper. At one time, I did not think much
of the people who smoke it. But when it comes to your health, it makes a big difference.
1.17
J.H.spoke at the IOM workshop in Washington, DC. He was was seriously injured in an
accident, suffers from a form of arthritis associated with abnormal activity of the
sympathetic nervous system known as reflex sympathetic dystrophy, and has hepatitis C. He
uses marijuana to relieve nausea from liver disease, pain, and muscle spasms.
- I am 48 years old, married with two children. I am a veteran who served during the
Vietnam War. I was exposed to hepatitis C in 1972 by a blood transfusion, which I needed
because of a motor-vehicle accident that broke my back, ruined my right shoulder, my left
thumb, and hand, and almost amputated my right leg at the knee. My hepatitis C was not
diagnosed until 1997 -- after the disease had destroyed my pancreasg and
I had four heart attacks, one angioplasty, and a minor stroke. In 1989, while at work, I
was involved in an accident with a large soil-survey auger. My pelvis was crushed, and
serious nerve damage was the result. I also have reflex sympathetic dystrophy, which is a
neurological disease that has a tremendous amount of pain and muscle spasms.
- I have reached what the doctors call end-stage liver disease from the hepatitis C. I
have lost 85 lbs due to the severe bouts of nausea and vomiting. Every time I come home
from a hospital stay, my 7-year-old asks if I got the liver transplant. I am on a
transplant list, but I am not a candidate until I am seven days from death.
- In October 1997, after trying four different antinausea medications, four of the doctors
that I see told me to go to Europe and see a doctor and try medicinal cannabis. My
primary-care doctor wrote me a letter to carry with my medical records asking that the
doctor help me in any way that he can to alleviate the symptoms of the hepatitis C and the
reflex sympathetic dystrophy. Those symptoms are severe nausea and pain from the hepatitis
C and pain and muscle spasms from the neurological disease.
- I went to Europe in November 1997, where I saw a doctor of internal medicine. He
prescribed me cannabis, 1-2 g a day. I got the medicine and a pipe and tried it. Within
two minutes of taking two puffs from the pipe, the nausea was gone. I don't think that I
felt the high, although I was quite elated. In about 45 min., I was starving. Normally, I
have a fear of eating because I vomit almost always after I eat or take a pill. I forgot
about that, and I think I ate more that night than I had eaten in months. I did feel a
little nauseated after about four hours, but I smoked two more puffs, and in about two
hours I went to bed. The next morning, I felt hungry. During my nine-day stay in Europe, I
was able to stay free of vomiting and the waves of nausea became less frequent.
- I had experienced four years of pain control using TegretolŪ, a drug used by epileptics
to control seizures. Now, I can't use that medication because of the damage that it causes
to my cirrhotic liver. When I smoked about two grams of marijuana a day, the nausea was
gone and I was no longer losing weight. The pain was at an acceptable level. Sometimes, I
still find it necessary to use an opiate pain-killer, but only when the pain is at its
worst. Surprisingly, I lost an associated high within a few days. I also think the
cannabis has an antidepressant effect on me, as I no longer have what I call the
"poor me" feelings that I experienced after learning about the hepatitis C.
g This is an unlikely consequence of hepatitis C; it is more likely
that the patient's liver was
damaged.
1.18
- The variety of stories presented left the study team with a clear view of people's
beliefs about how marijuana had helped them. But this collection of anecdotal data,
although useful, is limited. We heard many positive stories, but no stories from people
who had tried marijuana but found it ineffective. This is a fraction with an unknown
denominator. For the numerator, we have a sample of positive responses for the
denominator, we have no idea of the total number of people who have tried marijuana for
medical purposes. Hence, it is impossible to estimate the clinical value of marijuana or
cannabinoids in the general population based on anecdotal reports. Marijuana clearly seems
to relieve some symptoms for some people even if only as a placebo effect. But what is the
balance of harmful and beneficial effects? That is the essential medical question that can
be answered only by careful analysis of data collected under controlled conditions.
Cannabis and the cannabinoids
- Marijuana is the common name for Cannabis saliva, a hemp plant that grows throughout
temperate and tropical climates. The most recent review of the constituents of marijuana
lists 66 cannabinoids (table 1.5).16 But that does not mean that there are 66
different cannabinoid effects or interactions. Most of the cannabinoids are closely
related; they fall into only 10 groups of closely related cannabinoids, many of which
differ by only a single chemical moiety and might be midpoints along biochemical pathways
-- that is, degradation products, precursors, or byproducts.16 18 9-tetrahydrocannabinol
(9-THC) is the
primary psychoactive ingredient; depending on the particular plant, either THC or
cannabidiol is the most abundant cannabinoid in marijuana (figure 1.1) Throughout this
report, THC is used to indicate 9-THC. In the few cases where variants of THC are discussed, the
full names are used. All the cannabinoids are lipophilic -- they are highly soluble in
fatty fluids and tissues but not in water. Indeed, THC is so lipophilic that it is aptly
described as "greasy".
- Throughout this report, marijuana refers to unpurified plant extracts, including leaves
and flower tops, regardless of how they are consumed -- whether by ingestion or by
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 are included
among the effects of marijuana; but not all the effects of marijuana are necessarily due
to THC. Discussions concerning cannabinoids refer only to those particular compounds and
not to the plant extract. This distinction is important; it is often blurred or
exaggerated.
- cannabinoids are produced in epidermal glands on the leaves (especially the upper ones),
stems, and the bracts that support the flowers of the marijuana plant. Although the flower
itself has no epidermal glands, it has the highest cannabinoid content anywhere on the
plant, probably because of the accumulation of resin
1.19
secreted by the supporting bracteole (the small, leaf-like part below the flower). The
amounts of cannabinoids and their relative abundance in a marijuana plant vary with
growing conditions, including humidity, temperature, and soil nutrients (reviewed in Pate
199414). The chemical stability of cannabinoids in harvested plant material is
also affected by moisture, temperature, sunlight, and storage. They degrade under any
storage condition.
1.20
Figure 1.1 Cannabinoid Biosynthesis
Cannabinoid Biosynthesis
- Figure legend: Arrows indicate cannabinoid biosynthesis pathway; dark arrows indicate
established pathways, the light gray arrow indicates a probable, but not well established,
pathway (R. Mechoulam, personal communication, 1999).17 The great majority of
studies reporting on effects of cannabinoids refer to THC; most of the rest are about CBD
and CBN. Other cannabinoids found in marijuana do not appear to play an important role in
effects of marijuana.
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Table 1.5 cannabinoids Identified in Marijuana
| 66 Cannabinoids Identified in Marijuana |
| Cannabinoid Group |
Common Abbreviation |
Number of cannabinoid Variants known in each group |
| 9-tetrahydrocannabinol |
9-THC |
9 |
| 8-Tetrahydrocannabinol |
8-THC |
2 |
| Cannabichromene |
CBC |
5 |
| Cannabicyclol |
CBL |
3 |
| Cannabidiol |
CBD |
7 |
| Cannabielsoin |
CBE |
5 |
| Cannabigerol |
CBG |
6 |
| Cannabinidiol |
CBND |
2 |
| Cannabinol |
CBN |
7 |
| Cannabitriol |
CBT |
9 |
| Miscellaneous types |
. |
11 |
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Organization of the Report
- Throughout the report, steps that might be taken to fill the gaps in understanding both
the potential harms and benefits of marijuana and cannabinoid use will be identified.
Those steps include identifying knowledge gaps, promising research directions, and
potential therapies based on scientific advances in cannabinoid biology.
- Chapter 2 reviews basic cannabinoid biology and provides a foundation to understand the
medical value of marijuana or its constituent cannabinoids. In consideration of the
physician's first rule, "first, do no harm," the potential harms attributed to
the medical use of marijuana are reviewed before the potential medical benefits, chapter 3
reviews the risks posed by marijuana use, with emphasis on medical use.
- Chapter 4 analyzes the most credible clinical data relevant to the medical use of
marijuana. It reviews what is known about the physiological mechanisms underlying
particular conditions (for example, chronic pain, vomiting, anorexia, and muscle
spasticity), what is known about the cellular actions of cannabinoids, and the levels of
proof needed to show that marijuana is an effective treatment for specific symptoms. It
does not analyze the historical literature; history is informative in enumerating uses of
marijuana, but it does not provide the sort of information needed for a scientifically
sound evaluation of the efficacy and safety of marijuana for clinical use. Because
marijuana is advocated primarily as affording relief from the symptoms of disease rather
than as a cure, this chapter is organized largely by symptoms as opposed to disease
categories. Finally, chapter 4 compares the conclusions of this report with those of other
recent reports on the medical use of marijuana.
- Chapter 5 describes the process of and analyzes the prospects for cannabinoid drug
development.
1.23
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