By Lester Grinspoon
Harvard Medical School, 74 Fenwood Road, Boston, MA 02115, USA
Abstract - As the medical virtues of cannabis become
increasingly clear, the question of how to make it available to
patients becomes increasingly urgent. Conventional routes to
medical legitimacy -- the process by which pharmaceutical companies
satisfy government requirements for a new medicine -- are
inappropriate because of the unique history and properties of this
substance. Its full medical potential cannot be realized as long as
present prohibition laws are enforced. For medical as well as other
reasons, cannabis should be available to the public under
restrictions similar to those governing alcohol. Although early
changes in the law are unfortunately unlikely, increasing public
understanding of the medical usefulness of cannabis may lead to
changes in enforcement patters that bring the 60 year reign of
prohibition to a de facto conclusion.
"A new scientific truth does not triumph by convincing its
opponents and making them see the light, but rather because its
opponents eventually die and a new generation grows up that is
familiar with it." —- Max Planck
The medical value of marihuana has become increasingly clear to
many physicians and patients. There are three reasons for this.
First, it is remarkably non-toxic. Unlike most of the medicines in
the present pharmacopeia, it has never caused an overdose death.
Its short-term and long-term side effects are minimal compared to
medicines for which it will be substituted. Second, once patients
no longer have to pay the prohibition tariff, it will be much less
expensive than the medicines it replaces. Third, it is remarkably
versatile. Case histories and clinical experience suggest that it
is useful in the treatment of more than two dozen symptoms and
syndromes, and others will undoubtedly be discovered in the future.
As clinical evidence of marihuana's medical efficacy and safety
accumulates and first-hand experience of its value becomes more
common, the discussion is turning to how it should be made
available. When I first considered this issue in the early 1970s, I
thought the main problem was its classification in Schedule I of
the Comprehensive Drug Abuse and Control Act of 1970, which
describes it as having a high potential for abuse, no accepted
medical use in the United States, and lack of accepted safety for
use under medical supervision. At that time I naively believed that
a change to Schedule II would overcome a major obstacle, because
clinical research would be possible and prescriptions would
eventually be allowed.
I was the first witness at a joint meeting of the Drug Enforcement
Administration and the Food and Drug Administration that was
convened to consider a petition for rescheduling introduced by the
National Organization for the Reform of Marijuana Laws in 1972. At
that time I had already come to believe that the greatest harm in
recreational use of marihuana came not from the drug itself but
from the effects of prohibition. But I saw that as a separate
issue; I thought that, like opiates and cocaine, cannabis could be
used medically while remaining outlawed for other purposes. I also
thought that once it was transferred to Schedule II, research on
marihuana would be pursued eagerly, since it had shown such
interesting therapeutic properties. From this research we would
eventually be able to determine how it should be used medicinally,
how prescriptions could be provided, and who would be responsible
for quality control. Twenty-five years later, I have begun to doubt
this. It would be highly desirable if marihuana could be approved
as a legitimate medicine within the present federal regulatory
system, but it now seems to me unlikely.
First, I should note that cannabis has already been a legally
accepted medicine in the United States several times. Until 1941,
when it was dropped after the passage of the Marihuana Tax Act, it
was one of the drugs listed in the U.S. Pharmacopeia. If it had not
been removed at that time, it would have been grandfathered into
the Comprehensive Drug Abuse and Control Act as a prescription
drug, just as cocaine and morphine were. Again, in the late 1970s
and early 1980s, cannabis was used medically by hundreds of
patients (mainly in the form of synthetic tetrahydrocannabinol) in
projects conducted by several of the states for the treatment of
nausea and vomiting in cancer chemotherapy. This episode ended
because each state program had to comply with an enormous federal
paperwork burden that was more than the physicians and
administrators involved could bear. The federal government itself
approved the use of cannabis as a medicine in 1976 by instituting
the Compassionate IND program, under which physicians could obtain
an individual Investigational New Drug application (IND) for a
patient to receive cannabis. This program too was so
bureaucratically burdened that in the course of its history only
about three dozen patients ever received marihuana, and only eight
are still receiving it. When the program was discontinued
permanently in 1992, James O. Mason, the chief of the Public Health
Service, gave the following reason: "If it is perceived that the
Public Health Service is going around giving marihuana to folks,
there would be a perception that this stuff can't be so bad. It
gives a bad signal. I don't mind doing that if there is no other
way of helping these people...But there is not a shred of evidence
that smoking marihuana assists a person with AIDS." In effect, this
action was analogous to the recall of a prescription drug, without
any evidence of toxic effects to support it.
Today, even transferring marihuana to Schedule II would not be
enough to make it available as a prescription drug. Such drugs must
undergo rigorous, expensive, and time-consuming tests before they
are approved by the Food and Drug Administration for marketing as
medicines. The purpose is to protect the consumer by establishing
safety and efficacy. Because no drug is completely safe or always
efficacious, an approved drug has presumably satisfied a
risk-benefit analysis. When physicians prescribe for individual
patients they conduct an informal analysis of a similar kind,
taking into account not just the drug's overall safety and
efficacy, but its risk and benefits for a given patient with a
given condition. The formal drug approval procedures help to
provide physicians with the information they need to make this
analysis.
This system is designed to regulate the commercial distribution of
drug company products and protect the public against false or
misleading claims about their efficacy and safety. The drug is
generally a single synthetic chemical the company has developed and
patented. It submits an application to the Food and Drug
Administration and tests it first for safety in animals and then
for clinical efficacy and safety. The company must present evidence
from double-blind controlled studies showing that the drug is more
effective than a placebo and as effective as available drugs. Case
reports, expert opinion, and clinical experience are not considered
sufficient. The standards have been tightened since the present
system was established in 1962, and few applications that were
approved in the early 1960s would be approved today on the basis of
the same evidence.
Certainly we need more laboratory and clinical research to improve
our understanding of medicinal cannabis. We need to know how many
patients and which patients with each symptom or syndrome are
likely to find cannabis more effective than existing drugs. We also
need to know more about its effects on the immune system in
immunologically impaired patients, its interactions with other
medicines, and its possible uses for children.
But I have come to doubt whether the FDA rules should apply to
cannabis. There is no question about its safety. It is one of
humanity's oldest medicines, used for thousands of years by
millions of people with very little evidence of significant toxic
effects. More is known about its adverse effects than about those
of most prescription drugs. The American government has conducted a
decades-long multimillion-dollar research program in a futile
attempt to demonstrate toxic effects that would justify the
prohibition of cannabis as a nonmedical drug. Should time and
resources be wasted to demonstrate for the FDA what is already so
obvious?
As for efficacy, some believe that has been proven too, although
most disagree. During the 1970s and '80s several of the
state-sponsored research projects I mentioned suggested that
marihuana had advantages over both oral tetrahydrocannabinol and
other medicines in the treatment of nausea and vomiting from cancer
chemotherapy. But as long as the imprimatur of science can be given
only to rigorous double-blind controlled studies, the case for
marihuana has not been made. The assertion that it is a useful
medicine rests almost entirely on case reports and clinical
experience, just as it did in the late 19th and early 20th
centuries.
A double-blind controlled study may be the best way to prove the
relative value of a new medicine whose advantages over established
drugs are not obvious. But it is not the only way to demonstrate
efficacy. The focus of controlled trials is usually statistical
differences in effects in groups of patients, but medicine has
always been concerned mainly with individuals, whose needs can be
obscured in such experiments, especially when little effort is made
to identify distinctive characteristics that affect their
responses. The value of case reports and clinical experience is
often underestimated. They are the source of much of our knowledge
of synthetic medicines as well as plant derivatives. Controlled
experiments were not needed to recognize the therapeutic potential
of chloral hydrate, barbiturates, aspirin, curare, or lithium. The
therapeutic value of penicillin was widely recognized after it had
been given to only six patients. Similar evidence revealed the use
of propranolol for hypertension, diazepam for status epilepticus,
and imipramine for childhood enuresis. These drugs had originally
been approved by regulators for other purposes.
As early as 1976 several small and imperfect studies, not widely
known in the medical community, had shown that an aspirin a day
could prevent a second heart attack. In 1988 a large-scale
experiment demonstrated effects so dramatic that the researchers
decided to stop the experiment to publish the life-saving results.
On one estimate, as many as twenty thousand deaths a year might
have been prevented from the mid-1970s to the late-1980s if the
medical establishment had been quicker to recognize the value of
aspirin. The lesson is suggestive: marihuana, like aspirin, is a
substance known to be unusually safe and with enormous potential
medical benefits. There is one contrast, however; it was impossible
to be sure about the effect of aspirin on heart attacks without a
long-term study involving large numbers of patients, but
innumerable reports show that cannabis often brings immediate
relief of suffering that can be measured in a single person.
Case histories are, in a sense, simply the smallest research
studies, and the case reports on marihuana are numerous and
persuasive. There is an experimental method known as the N-of-1
clinical trial, or the single-patient randomized trial. In this
type of experiment, 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.
Some medical marihuana patients I know of carried out similar
experiments on themselves by alternating periods of cannabis use
with periods of no use. They had such symptoms as nausea and
vomiting, muscle spasms, compromised vision, seizures, and
debilitating pruritus. It is certain that cannabis won its
reputation as a medicine partly because many other patients around
the world have carried out the same kind of experiment. Admittedly,
in these experiments cannabis could not be administered completely
at random and there was no placebo, but in any case its
psychoactive effects are usually unmistakable, and few patients or
observers could be deceived by a placebo. Case histories and other
reports of clinical experience are sometimes disparagingly
dismissed as merely "anecdotal" evidence, which is said to be
irrelevant because only apparent successes are counted and failures
are ignored. It is true that cannabis may be useful for some people
with, say, multiple sclerosis, chronic pain, or depression, and not
for others. But cannabis is so safe that if even a few patients
with a given symptom could get that kind of relief, they should be
allowed access to it.
Even if it made sense to put marihuana through the FDA process,
there would be other problems in taking the conventional route to
medical legitimacy. As I have mentioned, FDA procedures are
designed for single chemical compounds, but marihuana is a plant
material containing many chemicals. Also, it is taken chiefly by
smoking, and no other drug in the present pharmacopeia is delivered
by this route. Furthermore, thousands of people are already getting
relief from cannabis, and they would not be risking severe
penalties if they did not believe that it was more useful than
conventional medicines. Can we expect them to put their pain and
suffering on hold for years while the established procedures grind
away?
Patients, their families, and others are becoming increasingly
impatient for a legal means of obtaining medical cannabis. The most
dramatic manifestation of this impatience has been the referenda
allowing distribution of medicinal cannabis that have been passed
in several states. In 1996 California became the first state to
approve such a law. Within weeks of the vote, more than a dozen
cannabis clubs opened to help sick people in need of relief, and
the membership of one quickly grew to 8,000. Many Americans believe
that this is the best temporary approach to the problem of making
medical cannabis available.
Among those who understand the present importance of the cannabis
clubs or cooperatives, there are two views on their organization.
One model follows the conventional delivery system for medicine:
the patient who needs medicinal cannabis (read medicine) goes to
the buyers club (read pharmacy) and presents a note from a
physician which certifies that the patient has a condition for
which the physician recommends cannabis (read prescription) to the
staff of the buyers club (read pharmacist). If both the doctor and
the buyers club behave responsibly and ethically, only those who
have a certified need for the medicine can receive it, and those
who are certified now have a reliable source. They are relieved of
the anxiety of having to find it on the street or grow their own.
In a buyers club of this kind, the patient is of course not
expected to take the medicine on the premises. In contrast, the
second distribution model resembles a social club more than a
pharmacy. The dispensing area is plastered with menus offering
types, grades, and prices. Large rooms are filled with brightly
colored posters, lounge chairs and sofas, tables, magazines, and
newspapers. While some people remain only long enough to buy their
medicine, most stay to smoke and talk. There are animated
conversations, laughter, music, and the pervasive pungent odor of
cannabis. The atmosphere is informal, welcoming, and warm,
providing support for patients who may be socially isolated and
have little opportunity to share concerns and feelings about their
illnesses. This type of club is a blend of Amsterdam-style
coffeehouse, American bar, and medical support group.
Most people who recognize the importance of the buyers clubs
believe that the first model, epitomized by the now closed Oakland
Club, is preferable to the second model, represented by the now
closed San Francisco Cultivators' Club. The San Francisco model,
largely because of the on-site cannabis smoking and relaxed
atmosphere, seems more casual in its commitment to confirming
medical need, and this has made even the supporters of buyers clubs
a little nervous. Yet the importance of the social aspect cannot be
underestimated. It is becoming increasingly clear that emotional
support—contacts with and help from friends, family,
co-workers, and others—plays an important role in
battling illness. This support improves the quality of life and may
even prolong the life of people with various illnesses, including
cancer. The San Francisco buyers club was not designed by
psychiatrists and social scientists to provide supportive group
therapy, but there is reason to believe it did. One of the
properties of marihuana may have contributed to its effectiveness:
when people use cannabis, they tend to be more sociable and find it
easier to share difficult thoughts and feelings. If there is even a
kernel of truth to the idea that talking about the stress,
setbacks, and triumphs in the battle against an illness can help a
patient cope and recover, it is clear that the San Francisco model
provides the best kind of environment for the dispensing of
marihuana.
Unfortunately, even many supporters of medical cannabis regarded
the language of California Proposition 215 as permitting the legal
use, cultivation, and distribution of marihuana too broadly. The
initiatives passed more recently in several states have more
tightly drawn limitations. They will not permit cannabis clubs with
the medical and psychiatric advantages of the San Francisco model,
and they allow such a short list of medical uses that only a few of
the patients who could find marihuana helpful will be allowed to
use it. But in any case, buyers clubs have to be regarded as a
stopgap measure. The federal government is not going to allow the
development of a separate distribution system for one medicine. It
has already succeeded in closing most of the California buyers
clubs, and if it is as successful elsewhere, they will not long
endure.
Other present approaches to making marihuana medically available
have even more serious drawbacks. Marihuana is now classified as a
Schedule I drug, which means that it is legally defined as too
dangerous for use even under medical supervision. But for the sake
of argument, let us suppose that the government comes to its senses
and marihuana is moved to Schedule II. This would allow
investigators to do the studies which lead to FDA approval for
medical use. But where will the money to finance these studies come
from? New medicines are usually introduced by drug companies, which
spend an estimated two hundred million dollars or more on the
development of each product. They are willing to undertake these
costs only because they hope for large profits during the 20 years
they own the patent. Obviously pharmaceutical companies cannot
patent marihuana and, in fact, may oppose its acceptance as a
medicine because it will compete with their own products. Only the
U.S. government has sufficient resources to explore medical
marihuana. But its record on the matter is, to put it mildly, not
reassuring. The government has opposed any loosening of
restrictions on clinical research with cannabis, including the
research needed for FDA approval. I believe the government will
ultimately have to provide some support for this research because
of public pressure, but it will arrive slowly. A study of marihuana
in the treatment of the AIDS wasting syndrome has recently been
approved and funded after four years of obstruction. But this
happened only because the political climate had changed after the
California initiative, and even so, the main subject of the study
had to be changed from medical efficacy to safety.
But let us suppose that studies are somehow completed showing that
marihuana is safe and effective as a treatment for the weight
reduction syndrome of AIDS, and physicians are able to prescribe it
for that condition. This will present unique problems. When a drug
is approved for one medical purpose, physicians are generally free
to write off-label prescriptions—that is, prescribe it
for other conditions as well. Dronabinol (Marinol), a synthetic
form of tetrahydrocannabinol, was approved as a prescription drug
in 1986 for the treatment of nausea and vomiting in cancer
chemotherapy, and later for the treatment of the weight reduction
syndrome of AIDS. However, presumably because it was thought to be
susceptible to medically questionable use, it became the first
FDA-approved drug for which off-label use was forbidden. The ban
has proved too difficult to enforce, and doctors have prescribed it
off-label, although somewhat timidly. If marihuana is approved as a
medicine, how will this concern about off-label prescriptions be
dealt with?
Present state and federal schemes for making cannabis medically
available invariably specify that it must be used for the treatment
of illnesses defined as "serious", "life-threatening", "terminal",
or "debilitating." Which of the many symptoms and syndromes for
which cannabis is useful should be considered "serious?" For
example, what about premenstrual syndrome? Surely women who suffer
from this disorder consider it a serious problem, and many of them
find that marihuana is the most useful treatment. What about
intractable hiccups or the loss of erectile capacity in
paraplegics? The people who suffer from these rare problems know
how debilitating they can be.
Generally speaking, the more dangerous a drug is, the more serious
or debilitating must be the symptom or illness for which it is
approved. Conversely, the more serious the health problem, the more
risk is tolerated. If the benefit is very large and the risk very
small, the medicine is distributed over the counter (OTC). OTC
drugs are considered so useful and safe that patients are allowed
to use their own judgment without a doctor's permission or advice.
Thus, today anyone can buy and use aspirin for any purpose at all.
This is permissible because aspirin is considered so safe; it takes
"only" one to two thousand lives a year in the United States. The
remarkably versatile ibuprofen and other NSAIDs can also be
purchased over the counter, because they too are considered very
safe; "only" 7,000 Americans lose their lives to these drugs
annually. Acetaminophen, another useful OTC drug, is responsible
for about 10% of cases of end-stage renal disease. The public is
also allowed to purchase many herbal remedies whose dangers have
not been determined and which probably have only placebo effects.
Compare these drugs with marihuana. Today no one can doubt that it
is, as DEA Administrative Judge Francis L. Young put it, "among the
safest therapeutic substances known to man." If it were now in the
official pharmacopeia, it would be a serious contender for the
title of least toxic substance in that compendium. In its long
history, marihuana has never caused a single overdose death. Yet
government schemes for its medical use are always cloaked in
language suggesting that it is too dangerous to be used except
under the most stringent limitations. In several states, medical
marihuana initiatives require patients to register, and in two
states they will need identification cards to protect them from
arrest.
As a Schedule II drug, marihuana would be classified as having a
high potential for abuse and limited medical use. Restrictions on
these drugs are becoming tighter. Nine states now require doctors
to make out prescriptions for many of them in triplicate so that
one copy can be sent to a centralized computer system that tracks
every transaction. In 1989 New York State added the benzodiazepines
(Valium and related drugs) to the list of substances monitored in
this way. Research has shown that since then many patients in New
York who have a legitimate need for benzodiazepines are being
denied them, and less safe and effective drugs are being
substituted. Increased regulation caused by fear of drug abuse has
been to the disadvantage rather than the advantage of patients.
In such situations physicians are often afraid to recommend what
they know or suspect to be the best medicine because they might
lose their reputations, licenses, and careers. Pharmacies might be
reluctant to carry marihuana as a Schedule II drug, and physicians
would hesitate to prescribe it. Through computer-based monitoring,
the DEA could know who was receiving prescription marihuana and how
much. It could hound physicians who by its standards prescribed
cannabis too freely or for off-label purposes the government
considered unacceptable. The potential for harassment would be
extremely discouraging. Unlike other Schedule II drugs such as
cocaine and morphine, cannabis has many potential medical uses.
Many patients might try to persuade their doctors that they had a
legitimate claim to a prescription. Physicians would not want the
responsibility of making such decisions if they were constantly
under threat of discipline by the state. A physician who prescribed
marihuana for chronic pain, for example, might be subjected to the
same harassment as those whom the DEA considers to be dispensing
opioids too liberally. Since the passage of the medical marihuana
initiative in California, I have heard from many patients who say
their doctors are afraid to recommend (not prescribe) marihuana
because of threats from the federal government—even
though those threats have been declared by the courts to be legally
baseless.
There is actually no case for the present
restrictions—unless third-party reefer-madness anxiety
counts as a risk. The Schedule II classification of cannabis would
not be accurate. It does not have a high potential for abuse, and
above all, it does not have limited medical uses. For example, a
physician might sensibly and safely prescribe it for muscle spasms
and chronic pain resulting from a variety of conditions, from
paraplegia to premenstrual syndrome. If the government and medical
licensing boards insist on tight restrictions, challenging
physicians as though cannabis were a dangerous drug every time it
is used for any new patient or any new purpose, there will be
constant conflict with one of two outcomes: patients do not get all
the benefits they should from this medicine, or they get the
benefits by abandoning the legal system for the black market or
their own outdoor or closet gardens.
Then there is the question of who will provide the cannabis. The
federal government now provides cannabis from its farm in
Mississippi to eight patients who have residual Compassionate INDs.
But surely the government could not or would not produce marihuana
for many thousands of patients receiving prescriptions, any more
than it does for other prescription drugs. But if production is
contracted out, will the farmers have to enclose their fields with
security fences? How would the marihuana be distributed? If through
pharmacies, how would they provide secure facilities capable of
keeping fresh supplies? When urine tests are demanded for workers,
how would patients who use marihuana legally as a medicine be
distinguished from those who use it for other (disapproved)
purposes?
If the full potential of cannabis as a medicine were to be achieved
in the setting of the present prohibition system, all of these
problems and more would have to be addressed. A delivery system
that successfully navigated this minefield would be so cumbersome,
inefficient, and bureaucratically top-heavy that patients would
continue to grow their own or buy it on the illicit market. The
authorities could claim that a legal medical distribution apparatus
existed, but most patients would find themselves in the same
situation they are in today. The Compassionate IND program, the
federal government's last scheme to satisfy these needs, lasted
from 1976 to 1992 but never supplied more than a few dozen patients
with cannabis.
Some believe a solution to the "medical marihuana problem"
(restricting the use of cannabis for medical purposes only) will be
found in the isolation of individual cannabinoids, the manufacture
of synthetic cannabinoids, and the development of analogs (chemical
cousins of cannabinoids). Supposedly, these drugs, sometimes in
combination, will make the natural product superfluous. Their use
in the form of parenterals, nasal sprays, vaporizers, skin patches,
pills, and suppositories will allegedly make it unnecessary to
expose the lungs to the particulate matter in marihuana smoke.
Furthermore, the commercial products may lack psychoactive effects,
which is apparently very important to some people. A pain
researcher at the Memorial Sloan-Kettering Cancer Institute
recently said that he was excited by the new analogs because "the
euphoria sparked by cannabinoids…is undesirable in
chronically ill patients."
Not everyone will agree that freedom from the psychoactive effects
is an advantage, but some cannabinoids and analogs may be
preferable to whole smoked or ingested marihuana for other reasons.
For example, cannabidiol may be more effective as an anti-anxiety
drug when it is taken without THC, which sometimes generates
anxiety. Other cannabinoid analogs may occasionally prove more
useful than marihuana because they can be administered
intravenously. For example, loss of consciousness occurs in 15% to
20% of patients who suffer a thrombotic or embolic stroke, an even
higher proportion after a hemorrhagic stroke, and some who develop
a brain syndrome after a severe blow to the head. The cannabinoid
analog dexanabinol (HU 211) has recently been shown to limit brain
swelling and protect brain cells from damage in these
circumstances. It is apparently not psychoactive and can be given
intravenously to an unconscious person.
The modern pharmaceutical laboratory will undoubtedly develop other
cannabinoid-related products with properties that whole marihuana
and marihuana extracts lack. There are already two known receptors
for cannabinoids with different anatomical distributions and only
partially overlapping functions. New agonists, antagonists, and
inverse agonists will be developed for these receptors (and
possibly for others still to be discovered), some of which may have
therapeutic potential. For example, tetrahydrocannabinol and
possibly other cannabinoids enhance appetite. Perhaps
pharmacologists will develop cannabinoid inverse tagonists which
inhibit appetite and act as nontoxic weight reduction medicines. A
better understanding of brain functions will also result from this
kind of research.
But these encouraging developments have a worrisome downside. South
American Indians have chewed the coca leaf for thousands of years
with little apparent abuse and few ill effects, but since the
isolation of methylbenzoylecgonine (cocaine) from the leaf's other
natural alkaloids, some users have developed serious problems.
Similarly, opium in its natural form is less risky than, say, the
potent synthetic opioid fentanyl. HU 211 (dexanabinol) is not
psychoactive, but its stereoisomer, HU 210, synthesized in the same
laboratory, is hundreds of times more psychoactive than THC. Other
analogs may be equally potent. The danger is that they will bear
the same relationship to marihuana that fentanyl bears to opium.
There are other reasons why isolated cannabinoids and cannabinoid
analogs will probably never completely displace marihuana itself as
a medicine. It was once widely believed that the availability of
dronabinol would make medical marihuana superfluous. Dronabinol is
packed in sesame oil, partly for easier absorption, but also
because it makes smoking impossible and therefore was thought to
make nonmedical use unlikely. But patients have generally not found
dronabinol to be nearly as useful as whole smoked marihuana. Even
among those who judge it equally effective, many find that street
marihuana is less expensive. If the advent of prescribable
dronabinol did not make marihuana medically obsolete, it is hard to
believe that the arrival of new analogs will do so. I believe that
many if not most patients who could get benefits from the new
analogs will choose instead to smoke the more easily accessible and
less expensive marihuana.
In evaluating the prospects for cannabis analogs, we must consider
what a pharmaceutical product requires for economic success.
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It must be as useful as or more useful than competitive
medicines for a particular symptom or syndrome, or it must have
a wide variety of approved medicinal uses.
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It must not have more undesirable side effects than
competitive medicines.
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It must have a mode of delivery which is as good as or
better than available alternatives.
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It must be priced competitively.
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It must have a risk-benefit ratio which is at least as good
as that of competitive medicines.
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It must not be restrictively scheduled under the federal
Comprehensive Drug Abuse and Control Act. The more restrictive
the schedule, the more serious impact on marketability and the
cost of development.
Now compare the anticipated analogs with whole marihuana:
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Except in a few situations, such as intravenous injection in
an unconscious person, analogs or combinations of analogs are
unlikely to be more useful than natural cannabis for most
specific symptoms. Nor are they likely to have a much wider
spectrum of therapeutic uses than the natural product, which
contains the cannabinoids (and synergistic combinations of
cannabinoids) from which the analogs are derived. In fact, one
result of the development of new analogs may be to identify new
medical uses for marihuana in its natural form. Shortly after
dexanabinol, which is both a potent antoxidant and an NMDA
antagonist, was found to protect brain cells against damage
after a stroke or trauma, it was shown that THC and
cannabidiol, also potent antoxidants, provide the same kind of
protection. In fact, given the urgency of retarding the
pathological process set in motion by a stroke or brain trauma,
it may be more medically sensible to allow patients with closed
head injuries to smoke the more accessible marihuana
immediately upon regaining consciousness as they await
transportation to a hospital to receive dexanabinol.
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The analogs may not cause such minor side effects as
inflammation of the sclera of the eyes or increased heart rate,
but these are not medically significant. Except for infrequent
orthostatic hypotension (faintness on standing up), pulmonary
exposure to smoke and, in the opinion of some, the psychoactive
effect (the high), marihuana has few medically significant side
effects.
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Inhalation devices now being perfected protect the lungs by
separating the cannabinoids in whole marihuana from burnt plant
products. When these devices are manufactured in large numbers,
they will provide an inexpensive, safe, and highly effective
means of delivery. Again, except for a few situations such as
unconsciousness and pulmonary impairment, it is doubtful that a
better means of delivery will be available for analogs.
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Given the cost of development, the new analogs will be
expensive. They will probably cost much more than whole smoked
marihuana even at the inflated prices imposed by the
prohibition tariff. Suppose, for example, that a new analog is
an antinauseant comparable to the prescription drug ondansetron
in effectiveness and price. Today a patient suffering from the
nausea of cancer chemotherapy might require one to four 8-mg
ondansetron pills at $30 to $40 apiece. Many patients will
probably get equally effective relief from a few puffs of a
marihuana cigarette—cost $5 at today's street
price, 30 cents if marihuana is produced as a medicine.
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The potential benefits of whole smoked marihuana are
extraordinarily high compared to the risks. For example, the
therapeutic ratio of marihuana is not known because it has
never caused an overdose death. It has been estimated on the
basis of extrapolation from animal data to be 20,000 to 40,000
to 1. Even if the therapeutic ratio of a new analog is also
high, it is unlikely to be as safe as whole marihuana because
it will be physically possible to ingest much more of the
analog.
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Any new cannabinoid analog with psychoactive properties
would presumably have to be placed in a restricted schedule by
the federal government. The Unimed Corporation, which makes
dronabinol, is now attempting to have it transferred from
Schedule II to Schedule III. That would allow physicians to
write prescriptions which could be refilled up to three times,
reducing the inconvenience and cost to the patient. Yet THC in
the form of dronabinol is chemically the same as the THC in
whole marihuana, which remains in Schedule I. It will become
increasingly difficult to justify such inconsistencies, which
might be regarded as hypocritical.
Ultimately, I do not believe the full potential of cannabinoids as
medicines can be realized through the use of prescription analogs
as long as the crushing, costly prohibition on natural marihuana is
maintained. Will prescription analogs be approved for all of the
present and future medical uses of whole cannabis? If not, will
off-label prescriptions of the analogs be allowed? And if
prescription drugs are available, will they always be sought? For
example, minor stomach upset is almost always quickly relieved with
a few puffs of cannabis. Will people suffering from this symptom go
to the trouble and expense of seeking a prescription? When it is
generally appreciated that marihuana usually relieves not only
gastric distress, but many other common symptoms such as headache,
insomnia, tension, pain and dysphoria, it may come to be regarded
much as aspirin is today.
In fact, the range of beneficial uses of marihuana is so broad that
it may ultimately be wrong to single out the strictly medical uses
for approval. Many people use it not only to ease everyday
discomforts, but also to heighten creativity or help them in their
work. It can serve as an intellectual stimulant, promote emotional
intimacy, or enhance the appreciation of food, sex, natural beauty,
music, and art. Cannabis use simply cannot be made to conform to
the boundaries established by present medical institutions. In this
case the demand for legal enforcement of a distinction between
medical and nonmedical use may be incompatible with the realities
of human need. I know that to say this is to invite the charge that
medical marihuana advocates are only using medicine as a stalking
horse for the legalization of nonmedical use. This false accusation
is actually a mirror image of the view taken by enemies of
marihuana. They are unwilling to admit that it can be a safe and
effective medicine largely because they are committed to
exaggerating its dangers when used for other purposes.
Nevertheless, it would be hypocritical to deny that there is a
connection. For 28 years I have been urging the legalization of
marihuana for general use. At one time I thought medical use could
be treated as a distinct issue, because even people who might never
see the urgency of legalizing nonmedical use would respond to
medical need. Now I have changed my mind. On the contrary, I
believe that making marihuana fully available as a medicine is one
of the reasons for general legalization.
Ideally, cannabis should be available under more or less the same
rules now applied to alcohol. At present, I fear, the political and
legal system is too ossified to accommodate that change. But I
believe enforcement of the laws against marihuana will be
increasingly neglected because of the same kind of public pressure
that has led to the enactment of the medical marihuana initiatives
in five states. If I am correct, anti-marihuana statutes will come
to resemble the laws against oral sex which still exist in several
states but are ignored so totally that most people do not even know
they exist. As the number of people arrested for possession
declines, cannabis in its natural form, along with isolated
cannabinoids and analogs, will be used more freely as a medicine.
As a result, the public will be in a better position to learn about
its virtues, and our understanding of those virtues will in turn
make the laws more difficult to enforce. I hope and expect that
this process will bring the era of prohibition to a de facto end.
Only then will it be possible to realize the full potential of this
remarkable substance, and its medical potential in particular.
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