"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 paper work 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 non medical 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.
(1) 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.
1.It must not have more undesirable side effects than competitive medicines.
2.It must have a mode of delivery which is as good as or better than available alternatives.
3.It must be priced competitively.
4.It must have a risk-benefit ratio which is at
least as good as that of competitive
medicines.
5.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:
1.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.
2.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.
3.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.
4.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.
5.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.
6.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.
