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B
etween 1840 and 1900, European and American medical
journals published more than 100 articles on the
therapeutic use of the drug known then as Cannabis indica
(or Indian hemp) and now as marihuana. It was recommended
as an appetite stimulant, muscle relaxant, analgesic,
hypnotic, and anti-convulsant. As late as 1913 Sir William
Osler recommended it as the most satisfactory remedy for
migraine.
Today the 5000-year medical history of cannabis has been
almost forgotten. Its use declined in the early 20th
century because the potency of preparations was variable,
responses to oral ingestion were erratic, and alternatives
became available--injectable opiates and, later, synthetic
drugs such as aspirin and barbiturates. In the United
States, the final blow was struck by the Marihuana Tax Act
of 1937. Designed to prevent non-medical use, this law made
cannabis so difficult to obtain for medical purposes that
it was removed from the pharmacopeia. It is now confined to
Schedule I under the Controlled Substances Act as a drug
that has a high potential for abuse, lacks an accepted
medical use, and is unsafe for use under medical
supervision.
In 1972 the National Organization for the Reform of
Marijuana Laws petitioned the Bureau of Narcotics and
Dangerous Drugs, later renamed the Drug Enforcement
Administration (DEA), to transfer marihuana to Schedule II
so that it could be legally prescribed. As the proceedings
continued, other parties joined, including the Physicians
Association for AIDS [acquired immunodeficiency syndrome]
Care. It was only in 1986, after many years of legal
maneuvering, that the DEA acceded to the demand for the
public hearings required by law. During the hearings, which
lasted 2 years, many patients and physicians testified and
thousands of pages of documentation were introduced. In
1988 the DEA's own administrative law judge, Francis L.
Young, declared that marihuana in its natural form
fulfilled the legal requirement of currently accepted
medical use in treatment in the United States. He added
that it was `one of the safest therapeutically active
substances known to man.'
(1)
His order that the marihuana plant be transferred to
Schedule II was overruled, not by any medical authority,
but by the DEA itself, which issued a final rejection of
all pleas for reclassification in March 1992.
Meanwhile, a few patients have been able to obtain
marihuana legally for therapeutic purposes. Since 1978,
legislation permitting patients with certain disorders to
use marihuana with a physician's approval has been enacted
in 36 states. Although federal regulations and procedures
made the laws difficult to implement, 10 states eventually
established formal marihuana research programs to seek Food
and Drug Administration (FDA) approval for Investigational
New Drug (IND) applications. These programs were later
abandoned, mainly because the bureaucratic burden on
physicians and patients became intolerable.
Growing demand also forced the FDA to institute an
Individual Treatment IND (commonly referred to as a
Compassionate IND) for the use of physicians whose patients
needed marihuana because no other drug would produce the
same therapeutic effect. The application process was made
enormously complicated, and most physicians did not want to
become involved, especially since many believed there was
some stigma attached to prescribing cannabis. Between 1976
and 1988 the government reluctantly awarded about a half
dozen Compassionate INDs for the use of marihuana. In 1989
the FDA was deluged with new applications from people with
AIDS, and the number granted rose to 34 within a year. In
June 1991, the Public Health Service announced that the
program would be suspended because it undercut the
administration's opposition to the use of illegal drugs.
After that no new Compassionate INDs were granted, and the
program was discontinued in March 1992. Eight patients are
still receiving marihuana under the original program; for
everyone else it is officially a forbidden medicine.
And yet physicians and patients in increasing numbers
continue to relearn through personal experience the lessons
of the 19th century. Many people know that marihuana is now
being used illegally for the nausea and vomiting induced by
chemotherapy. Some know that it lowers intraocular pressure
in glaucoma. Patients have found it useful as an
anticonvulsant, as a muscle relaxant in spastic disorders,
and as an appetite stimulant in the wasting syndrome of
human immunodeficiency virus infection. It is also being
used to relieve phantom limb pain, menstrual cramps, and
other types of chronic pain, including (as Osler might have
predicted) migraine.
(2)
Polls and voter referenda have repeatedly indicated that
the vast majority of Americans think marihuana should be
medically available.
One of marihuana's greatest advantages as a medicine is
its remarkable safety. It has little effect on major
physiological functions. There is no known case of a lethal
overdose; on the basis of animal models, the ratio of
lethal to effective dose is estimated as 40,000 to 1. By
comparison, the ratio is between 3 and 50 to 1 for
secobarbital and between 4 and 10 to 1 for ethanol.
Marihuana is also far less addictive and far less subject
to abuse than many drugs now used as muscle relaxants,
hypnotics, and analgesics. The chief legitimate concern is
the effect of smoking on the lungs. Cannabis smoke carries
even more tars and other particulate matter than tobacco
smoke. But the amount smoked is much less, especially in
medical use, and once marihuana is an openly recognized
medicine, solutions may be found. Water pipes are a partial
answer; ultimately a technology for the inhalation of
cannabinoid vapors could be developed. Even if smoking
continued, legal availability would make it easier to take
precautions against aspergilli and other pathogens. At
present, the greatest danger in medical use of marihuana is
its illegality, which imposes much anxiety and expense on
suffering people, forces them to bargain with illicit drug
dealers, and exposes them to the threat of criminal
prosecution.
The main active substance in cannabis,
D(9)-tetrahydrocannabinol (THC), has been available for
limited purposes as a Schedule II synthetic drug since
1985. This medicine, dronabinol (Marinol), taken orally in
capsule form, is sometimes said to obviate the need for
medical marihuana. Patients and physicians who have tried
both disagree. The dosage and duration of action of
marihuana are easier to control, and other cannabinoids in
the marihuana plant may modify the action of THC. The
development of cannabinoids in pure form should certainly
be encouraged, but the time and resources required are
great and at present unavailable. In these circumstances,
further isolation, testing, and development of individual
cannabinoids should not be considered a substitute for
meeting the immediate needs of suffering people.
Although it is often objected that the medical
usefulness of marihuana has not been demonstrated by
controlled studies, several informal experiments involving
large numbers of subjects suggest an advantage for
marihuana over oral THC and other medicines. For example,
from 1978 through 1986 the state research program in New
Mexico provided marihuana or synthetic THC to about 250
cancer patients receiving chemotherapy after conventional
medications failed to control their nausea and vomiting. A
physician who worked with the program testified at a DEA
hearing that for these patients marihuana was clearly
superior to both chlorpromazine and synthetic THC.
(3)
It is true that we do not have studies controlled according
to the standards required by the FDA--chiefly because
legal, bureaucratic, and financial obstacles are constantly
put in the way. The situation is ironical, since so much
research has been done on marihuana, often in unsuccessful
attempts to prove its dangerous and addictive character,
that we know more about it than about most prescription
drugs.
Physicians should offer more encouragement to controlled
research, but it too has limitations. Individual
therapeutic responses can be obscured by the statistical
results of group experiments in which there is little
effort to identify the specific features of a patient that
affect the drug response. Furthermore, much of our
knowledge of synthetic medicines as well as plant
derivatives comes from anecdotal evidence. For example, as
early as 1976 several small, methodologically imperfect,
and relatively obscure studies had shown that taking an
aspirin a day could prevent a second heart attack. In 1988
a large-scale experiment demonstrated dramatic effects.
This story is suggestive, because marihuana, like aspirin,
is a substance known to be unusually safe and to have
enormous potential health benefits.
Cannabis can also bring about immediate relief of
suffering measurable in a study with only one subject. In
the experimental method known as the single-patient
randomized trial, active and placebo treatments are
administered randomly in alternation or succession to a
patient. The method is often useful when large-scale
controlled studies are impossible or inappropriate because
the disorder is rare, the patient is atypical, or the
response to the treatment is idiosyncratic. Many patients,
either deliberately or because of unreliable supplies, have
informally carried out somewhat similar experiments by
alternating periods of cannabis use with periods of no use
in the treatment of various disorders.
(2)
(pp133-136)
The American Medical Association was one of the few
organizations that raised a voice in opposition to the
Marihuana Tax Act of 1937, yet today most physicians seem
to take little active interest in the subject, and their
silence is often cited by those who are determined that
marihuana shall remain a forbidden medicine. Meanwhile,
many physicians pretend to ignore the fact that their
patients with cancer, AIDS, or multiple sclerosis are
smoking marihuana for relief; some quietly encourage them.
In a 1990 survey, 44% of oncologists said they had
suggested that a patient smoke marihuana for relief of the
nausea induced by chemotherapy.
(4)
If marihuana were actually unsafe for use even under
medical supervision, as its Schedule I status explicitly
affirms, this recommendation would be unthinkable. It is
time for physicians to acknowledge more openly that the
present classification is scientifically, legally, and
morally wrong.
Physicians have both a right and a duty to be skeptical
about therapeutic claims for any substance, but only after
putting aside fears and doubts connected with the stigma of
illicit non-medical drug use. Advocates of medical use of
marihuana are sometimes charged with using medicine as a
wedge to open a way for `recreational' use. The accusation
is false as applied to its target, but expresses in a
distorted form a truth about some opponents of medical
marihuana: they will not admit that it can be a safe and
effective medicine largely because they are stubbornly
committed to exaggerating its dangers when used for
non-medical purposes.
We are not asking readers for immediate agreement with
our affirmation that marihuana is medically useful, but we
hope they will do more to encourage open and legal
exploration of its potential. The ostensible indifference
of physicians should no longer be used as a justification
for keeping this medicine in the shadows.
Lester Grinspoon, MD
James B. Bakalar, JD
NOTES
From the Department of Psychiatry, Harvard Medical
School, and the Massachusetts Mental Health Center,
Boston. Reprint requests to Harvard Medical School, 74
Fenwood Rd, Boston, MA 02215 (Dr. Grinspoon)
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