Testimony of
Lester Grinspoon, M.D.
Associate Professor of Psychiatry, Harvard Medical School
before the Crime Subcommittee of the Judiciary Committee
U.S. House of Representatives
Washington, D.C.
October 1, 1997
Mr. Chairman and members of the subcommittee, I appreciate the opportunity
to appear before you this morning to share my views on the use of marihuana as
a medicine.
In September 1928 Alexander Fleming returned from vacation to his laboratory
and discovered that one of the Petri dishes he had inadvertently left out over
the summer was overgrown with staphylococci except for the area surrounding a
mold colony. That mold contained a substance he later named penicillin. He
published his finding in 1929, but the discovery was ignored by the medical
establishment, and bacterial infections continued to be a leading cause of
death. Had it aroused the interest of a pharmaceutical firm, its development
might not have been delayed. More than 10 years later, under wartime pressure
to develop antibiotic substances to supplement sulfonamide, Howard Florey and
Ernst Chain initiated the first clinical trial of penicillin (with six
patients) and began the systematic investigations that might have been
conducted a decade earlier.1
After its debut in 1941, penicillin rapidly earned a reputation as "the
wonder drug of the '40s." There were three major reasons for that
reputation: it was remarkably non-toxic, even at high doses; it was inexpensive
to produce on a large scale; and it was extremely versatile, acting against the
microorganisms that caused a great variety of diseases, from pneumonia to
syphilis. In all three respects cannabis suggests parallels:
(1) Cannabis is remarkably safe. Although not harmless, it is surely less toxic
than most of the conventional medicines it could replace if it were legally
available. Despite its use by millions of people over thousands of years,
cannabis has never caused an overdose death. The most serious concern is respiratory
system damage from smoking, but that can easily be addressed by increasing the
potency of cannabis and by developing the technology to separate the
particulate matter in marihuana smoke from its active ingredients, the
cannabinoids (prohibition, incidentally, has prevented this technology from
flourishing). Once cannabis regains the place in the U.S. Pharmacopoeia that it
lost in 1941 after the passage of the Marihuana Tax Act (1937), it will be
among the least toxic substances in that compendium. Right now the greatest
danger in using marihuana medically is the illegality that imposes a great deal
of anxiety and expense on people who are already suffering.
(2) Medical cannabis would be extremely inexpensive. Street marihuana today
costs $200 to $400 an ounce, but the prohibition tariff accounts for most of
that. A reasonable estimate of the cost of cannabis as a medicine is $20 to $30
an ounce, or about 30 to 40 cents per marihuana cigarette. As an example of
what this means in practice, consider the following. Both the marihuana
cigarette and an 8 mg ondansetron pill -- cost to the patient, $30 to $40 --
are effective in most cases for the nausea and vomiting of cancer chemotherapy
(although many patients find less than one marihuana cigarette to be more
useful, and they often require several ondansetron pills). Thus cannabis would
be at least 100 times less expensive than the best present treatment for this
symptom.
(3) Cannabis is remarkably versatile. Let me review briefly some of the
symptoms and syndromes for which it is useful.
Cancer Treatment
Cannabis has several uses in the treatment of cancer. As an appetite stimulant,
it can help to slow weight loss in cancer patients.2 It may also act
as a mood elevator. But the most common use is the prevention of nausea and
vomiting of cancer chemotherapy. About half of patients treated with anticancer
drugs suffer from severe nausea and vomiting, which are not only unpleasant but
a threat to the effectiveness of the therapy. Retching can cause tears of the
esophagus and rib fractures, prevent adequate nutrition, and lead to fluid
loss. Some patients find the nausea so intolerable they say they would rather
die than go on. The antiemetics most commonly used in chemotherapy are
metoclopramide (Reglan), the relatively new ondansetron (Zofran), and the newer
granisetron (Kytril). Unfortunately, for many cancer patients these
conventional antiemetics do not work at all or provide little relief.
The suggestion that cannabis might be useful arose in the early 1970s when some
young patients receiving cancer chemotherapy found that marihuana smoking
reduced their nausea and vomiting. In one study of 56 patients who got no
relief from standard antiemetic agents, 78% became symptom-free when they
smoked marihuana.3 Oral tetrahydrocannabinol (THC)has proved
effective where the standard drugs were not.4,5 but smoking
generates faster and more predictable results because it raises THC
concentration in the blood more easily to the needed level. Also, it may be
hard for a nauseated patient to take oral medicine. In fact, there is strong
evidence that most patients suffering from nausea and vomiting prefer smoked
marihuana to oral THC.2
Oncologists may be ahead of other physicians in recognizing the therapeutic
potential of cannabis. In the spring of 1990, two investigators randomly
selected more than 2,000 members of the American Society of Clinical Oncology
(one-third of the membership) and mailed them an anonymous questionnaire to
learn their views on the use of cannabis in cancer chemotherapy. Almost half of
the recipients responded. Although the investigators acknowledge that this
group was self-selected and that there might be a response bias, their results
provide a rough estimate of the views of specialists on the use of Marinol
(dronabinol, oral synthetic THC) and smoked marihuana.
Only 43% said the available legal antiemetic drugs (including Marinol) provided
adequate relief to all or most of their patients, and only 46% said the side
effects of these drugs were rarely a serious problem. Forty-four percent had
recommended the illegal use of marihuana to at least one patient, and half
would prescribe it to some patients if it were legal. On average, they
considered smoked marihuana more effective than Marinol and roughly as safe.6
Glaucoma
Cannabis may also be useful in the treatment of glaucoma, the second leading
cause of blindness in the United States. In this disease, fluid pressure within
the eyeball increases until it damages the optic nerve. About a million
Americans suffer from the form of glaucoma (open angle) treatable with
cannabis. Marihuana causes a dose-related, clinically significant drop in
intraocular pressure that lasts several hours in both normal subjects and those
with the abnormally high ocular tension produced by glaucoma. Oral or
intravenous THC has the same effect, which seems to be specific to cannabis
derivatives rather than simply a result of sedation. Cannabis does not cure the
disease, but it can retard the progressive loss of sight when conventional
medication fails and surgery is too dangerous.7
Seizures
About 20% of epileptic patients do not get much relief from conventional
anticonvulsant medications. Cannabis has been explored as an alternative at
least since 1975 when a case was reported in which marihuana smoking, together
with the standard anticonvulsants phenobarbital and diphenylhydantoin, was
apparently necessary to control seizures in a young epileptic man.8
The cannabis derivative that is most promising as an anticonvulsant is
cannabidiol. In one controlled study, cannabidiol in addition to prescribed
anticonvulsants produced improvement in seven patients with grand mal
convulsions; three showed great improvement. Of eight patients who received a
placebo instead, only one improved.9 There are patients suffering
from both grand mal and partial seizure disorders who find that smoked
marihuana allows them to lower the doses of conventional anticonvulsant
medications or dispense with them altogether.2
Pain
There are many case reports of marihuana smokers using the drug to reduce pain:
post-surgery pain, headache, migraine, menstrual cramps, and so on. Ironically,
the best alternative analgesics are the potentially addictive and lethal
opioids. In particular, marihuana is becoming increasingly recognized as a drug
of choice for the pain that accompanies muscle spasm, which is often chronic
and debilitating, especially in paraplegics, quadriplegics, other victims of
traumatic nerve injury, and people suffering from multiple sclerosis or
cerebral palsy. Many of them have discovered that cannabis not only allows them
to avoid the risks of other drugs, but also reduces muscle spasms and tremors;
sometimes they are even able to leave their wheelchairs.10
One of the most common causes of chronic pain is osteoarthritis, which is
usually treated with synthetic analgesics. The most widely used of these drugs
-- aspirin, acetaminophen (Tylenol), and nonsteroidal antiinflammatory drugs
(NSAIDs) like ibuprofen and naproxen -- are not addictive, but they are often
insufficiently powerful. Furthermore, they have serious side effects. Stomach
bleeding and ulcer induced by aspirin and NSAIDs are the most common serious
adverse drug reactions reported in the United States, causing an estimated
7,000 deaths each year.
Acetaminophen can cause liver damage or kidney failure when used regularly for
long periods of time; a recent study suggests it may account for 10% of all
cases of end-stage renal disease, a condition that requires dialysis or a
kidney transplant.11,12 Marihuana, as I pointed out earlier, has
never been shown to cause death or serious illness.
AIDS More than 300,000 Americans have died of AIDS. Nearly a
million are infected with HIV, and at least a quarter of a million have AIDS.
Although the spread of AIDS has slowed among homosexual men, the reservoir is
so huge that the number of cases is sure to grow. Women and children as well as
both heterosexual and homosexual men are now being affected; the disease is
spreading most rapidly among intravenous drug abusers and their sexual
partners. The disease can be attacked with anti-viral drugs, of which the best
known are zidovudine (AZT) and protease inhibitors.
Unfortunately, these drugs sometimes cause severe nausea that heightens the
danger of semi-starvation for patients who are already suffering from nausea
and losing weight because of the illness -- a condition sometimes called the
AIDS wasting syndrome.
Marihuana is particularly useful for patients who suffer from AIDS because it
not only relieves the nausea but retards weight loss by enhancing appetite.
When it helps patients regain lost weight, it can prolong life. Marinol has
been shown to relieve nausea and retard or reverse weight loss in patients with
HIV infection, but most patients prefer smoked cannabis for the same reasons
that cancer chemotherapy patients prefer it: it is more effective and has fewer
unpleasant side effects, and the dosage is easier to adjust.,br> These are
the symptoms and syndromes for which cannabis is most commonly used today, but
there are others for which clinical experience provides compelling evidence. It
is distressing to consider how many lives might have been saved if penicillin
had been developed as a medicine immediately after Fleming's discovery. It is
equally frustrating to consider how much suffering might have been avoided if
cannabis had been available as a medicine for the last 60 years. Initial
enthusiasm for drugs is often disappointed after further investigation, but
this is hardly likely in the case of cannabis, since it is not a new medicine
at all. Its long medical history began 5,000 years ago in China and extended
well into the twentieth century. Between 1840 and 1900, more than one hundred
papers on its therapeutic uses were published in American and European medical
journals. It was recommended as an appetite stimulant, muscle relaxant,
analgesic, sedative, anticonvulsant, and treatment for opium addiction. As late
as 1913, the great Sir William Osler cited it as the best remedy for migraine
in a standard medical textbook.
In the United States, what remained of marihuana's medical use was effectively
eliminated by the Marihuana Tax Act of 1937, which was ostensibly designed to
prevent nonmedical use but made cannabis so difficult to obtain that it was
removed from standard pharmaceutical references. When the present comprehensive
federal drug law was passed in 1970, marihuana was officially classified as a
Schedule I drug: a high potential for abuse, no accepted medical use, and lack
of safety for use under medical supervision.
But in the 1970s the public began to rediscover its medical value, as letters
appeared in lay publications from people who had learned that it could relieve
their asthma, nausea, muscle spasms, or pain and wanted to shared that
knowledge with readers who were familiar with the drug. The most effective spur
to the movement for medical marihuana came from the discovery that it could prevent
the AIDS wasting syndrome. It is not surprising that the Physicians Association
for AIDS Care was one of the medical organizations that endorsed the California
initiative prohibiting criminal prosecution of medical marihuana users. The
mid-1980s had already seen the establishment, often by people with AIDS, of
cannabis buyers' clubs, organizations that distribute medical marihuana in open
defiance of the law. These clubs buy marihuana wholesale and provide it to
patients at or near cost, usually on the written recommendation of a physician.
Although a few of the clubs have been raided and closed, most are still
flourishing, and new ones are being organized. Some of them may gain legal
status as a result of the initiative.
Until the recent vote in California, efforts to change the laws had been
futile. In 1972 the National Organization for the Reform of Marijuana Laws
(NORML) entered a petition to move marihuana out of Schedule I under federal
law so that it could become a prescription drug. It was not until 1986 that the
Drug Enforcement Administration (DEA) finally agreed to the public hearings
required by law. During two years of hearings, many patients and physicians
testified and thousands of pages of documentation were introduced. In 1988 the
DEA's Administrative Law Judge, Francis L. Young, declared that marihuana
fulfilled the requirement for transfer to Schedule II. In his opinion he
described it as "one of the safest therapeutically active substances
known to man." His order was overruled by the DEA.
Nevertheless, a few patients have been able to obtain medical marihuana legally
in the last twenty years. Beginning in the 1970s, thirty-five states passed
legislation that would have permitted medical use of cannabis but for the
federal law. Several of those states actually established special research
programs, with the permission of the federal government, under which patients
who were receiving cancer chemotherapy would be allowed to use cannabis. These
projects demonstrated the value of both smoked marihuana and oral THC. The FDA
then approved oral THC as a prescription medicine, but ignored the data that
suggested that smoked marihuana was more useful than oral THC for some
patients. With the approval of Marinol, this research came to an end. In 1976,
the federal government introduced the Individual Treatment Investigational New
Drug program (commonly referred to as the Compassionate IND), which provided
marihuana to a few patients whose doctors were willing to undergo the
paperwork-burdened and time-consuming application process. About three dozen
patients eventually received marihuana before the program was discontinued in
1992, and eight survivors are still receiving it -- the only persons in the
country for whom it is not a forbidden medicine. It is safe to say that a
significant number of the more than ten million American citizens arrested on
marihuana charges in the last thirty years were using the drug therapeutically.
The Schedule I classification persists, although in my view and the view of
millions of other Americans, it is medically absurd, legally questionable, and
morally wrong.
Opponents of medical marihuana often object that the evidence of its
usefulness, although strong, comes only from case reports and clinical
experience. It is true that there are no double-blind controlled studies
meeting the standards of the Food and Drug Administration, chiefly because
legal, bureaucratic, and financial obstacles have been constantly put in the
way. The situation is ironical, since so much research has been done on
marihuana, often in unsuccessful efforts to show health hazards and addictive
potential, that we know more about it than about most prescription drugs. In
any case, individual therapeutic responses are often obscured in group experiments,
and case reports and clinical experience are the source of much of our
knowledge of drugs. As Dr. Louis Lasagna has pointed out, controlled
experiments were not needed to recognize the therapeutic potential of chloral
hydrate, barbiturates, aspirin, insulin, or penicillin.13 Nor was
that the way we learned about the use of propranolol for hypertension, diazepam
for status epilepticus, and imipramine for enuresis. All these drugs had
originally been approved for other purposes.
In the experimental method known as the single patient randomized trial, active
and placebo treatments are administered randomly in alternation or succession.
The method is often used when large-scale controlled studies are inappropriate
because the disorder is rare, the patient is atypical, or the response to
treatment is idiosyncratic.14 Several patients have told me that
they assured themselves of marihuana's effectiveness by carrying out such
experiments on themselves, alternating periods of cannabis use with periods of
abstention. I am convinced that the medical reputation of cannabis is derived
partly from similar experiments conducted by many other patients.
Some physicians may regard it as irresponsible to advocate use of a medicine on
the basis of case reports, which are sometimes disparaged as merely
"anecdotal" evidence which counts apparent successes and ignore
apparent failures. That would be a serious problem only if cannabis were a
dangerous drug. The years of effort devoted to showing that marihuana is exceedingly
dangerous have proved the opposite. It is safer, with fewer serious side
effects, than most prescription medicines, and far less addictive or subject to
abuse than many drugs now used as muscle relaxants, hypnotics, and analgesics.
Thus cannabis should be made available even if only a few patients could get
relief from it, because the risks would be so small. For example, as I
mentioned, many patients with multiple sclerosis find that cannabis reduces
their muscle spasms and pain. A physician may not be sure that such a patient
will get more relief from marihuana than from the standard drugs baclofen,
dantrolene, and diazepam -- all of which are potentially dangerous or addictive
-- but it is almost certain that a serious toxic reaction to marihuana will not
occur. Therefore the potential benefit is much greater than any potential risk.
During the past few years, the medical uses of marihuana have become
increasingly clear to many physicians and patients, and the number of people
with direct experience of these uses has been growing. Therefore the discussion
is now turning from whether cannabis is an effective medicine to how it should
be made available. It is essential to relax legal restrictions that prevent
physicians and patients from achieving a workable accommodation that takes into
account the needs of suffering people. H.R. 1782 (the Medical Use of Marihuana
Act) is a worthwhile move in that direction because it gets the federal
government out of the way and allows the states to experiment with their own solutions
to the problem. I strongly urge that you pass this law.
REFERENCES 1. Hayes, G.W., et al., The golden anniversary
of the silver bullet.
Journal of the American Medical Association 1993;270:13:1610-1611.
2. Grinspoon L, Bakalar JB. Marihuana, the Forbidden Medicine, Revised and Expanded Edition. New Haven: Yale University Press, 1997.
3. Vinciguerra, V., et al. Inhalation marihuana as an antiemetic for cancer chemotherapy. New York State Journal of Medicine 1988;88:525-527.
4. Sallan, S.E., et al. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. New England Journal of Medicine 1975;293:795-797.
5. Chang, A.E., et al. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate: a prospective, randomized evaluation. Annals of Internal Medicine 1979;91:819-824.
6. Doblin R, Kleiman M. Marihuana as anti-emetic medicine: a survey of oncologists' attitudes and experiences. Journal of Clinical Oncology 1991;9:1275-80.
7. Hepler, R.S., et al. Ocular effects of marihuana smoking. In M.C. Braude, S. Szara (eds.). Pharmacology of Marihuana. New York: Raven Press, 1976.
8. Consroe, Paul F., et al. Anticonvulsant nature of marihuana smoking. Journal of the American Medical Association 1975;234:306-307.
9. Cunha, J.M., et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 1980;21:175-185.
10. Petro, D.J. Marihuana as a therapeutic agent for muscle spasm or spasticity. Psychosomatics 1980;21:81-85.
11. Singh, G., Ramey, D.R. Morfeld, D. Shi, H. Hatoum, H.T., Fries, J.F. Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. Archives of Internal Medicine 1996;156:1530-1536.
12. Perneger, T.V., Whelton, P., Klag, M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. New England Journal of Medicine 1994; 331:25:1675-1679.
13. Lasagna, L. Clinical trials in the natural environment. In C. Stiechele, W. Abshagen, J. Kich-Weser (eds.). Drugs Between Research and Regulations. New York: Springer-Verlag, 1985: 45-49.
14. Larson, E.B. N-of-1 clinical trials: A technique for improving medical therapeutics. Western Journal of Medicine 1990;152:52-56; Guyatt, G.H., Keller, J.L., Jaeschke, R., et al. The N-of-1 randomized controlled trial: Clinical usefulness. Annals of Internal Medicine 1990;112:293-299.
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