Marihuana as Medicine: A Plea for Reconsideration
 
Grinspoon, Lester, and James B. Bakalar. "Marihuana
as Medicine: A Plea for Reconsideration." Editorial. _Journal
of the American Medical Association_ 273.23 (1995): 1875-76.
 
BETWEEN 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 
([unprintable]/9/-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 [unprintable]/9/-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 [unprintable]/9/-THC and other medicines. 
For example, from 1978 through 1986 the state research program 
in New Mexico provided marihuana or synthetic [unprintable]/9/-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 [unprintable]/9/-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
1. In the Matter of Marihuana 
Rescheduling Petition, Docket 86-22, Opinion, Recommended Ruling, 
Findings of Fact, Conclusions of Law, and Decision of Administrative 
Law Judge, September 6, 1988. Washington, DC: Drug Enforcement 
Agency; 1988.
2. Grinspoon L, Bakalar J. _Marihuana, 
the Forbidden Medicine_. New Haven, Conn.: Yale University Press; 
1993.
2a. Grinspoon, Bakalar, (pp. 133-136).
3. In the Matter of Marihuana 
Rescheduling Petition, Docket 86-22, Affidavit of Daniel Dansac, 
M.D. Washington, DC: Drug Enforcement Agency; 1987.
4. Doblin R., Kleiman Mark. "Marihuana 
as anti-emetic medicine: a survey of oncologists' attitudes and 
experiences". J Clin. Oncol. 1991; 9:1275-1290.
[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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