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A
s an issue on the cusp of science and social policy,
the value of marijuana in medicine refuses to go away. For
several years, researchers wishing to undertake clinical
trials of marijuana's medical effects on humans have
claimed that the National Institute on Drug Abuse (NIDA),
the White House Office of National Drug Control Policy
(ONDCP), and the Food and Drug Administration (FDA) are
stonewalling by insisting that the protocols are
unacceptable. Those organizations complain that several
proponents of clinical trials have failed to understand the
complexity of the issue and have been unwilling to change
their protocols. ONDCP has warned physicians in states
whose voters have approved initiatives that back the
concept of prescribing marijuana for medical purposes that
they risk losing their licenses if they follow that
advice.
A new report from the Institute of Medicine should
define the issue more tightly.(1) It may also stimulate
clinical trials somewhat different from those advocated to
date. The report concludes that cannabinoids, marijuana's
active components, have potential applicability for some
human symptoms. However, it also suggests that those
components should be delivered by a mechanism other than
inhaling smoke. The report recommends that any clinical
trials of smoked marijuana should be short, approved by
institutional review boards, and applied only to patients
most likely to benefit from the treatment.
"We say basically that we believe the future is
nonsmoked, inhaled molecules--inhaled from marijuana or
synthesized," says Stanley J. Watson Jr., codirector of the
University of Michigan's Mental Health Research Institute
and co-principal investigator of the report. "We can
imagine situations where you might want to start with a
short-term study with cannabinoids in the form of a
cigarette. But we feel there should be a time limit on
those studies."
In fact, the report provides some solace for both sides
in the prickly debate. And both sides quickly claimed
credit. "The scientific evidence in the report shows that
marijuana is relatively safe and effective medicine for
many patients," asserts Chuck Thomas, codirector of the
Marijuana Policy Project, an advocacy group in Washington,
D.C., that favors marijuana usage. "The smoked-marijuana
community should see this study as a nail in the coffin,"
retorts Eric Voth, chairman of the International Drug
Strategy Institute, based in Topeka, Kan. "It says that any
kind of research needs to be done with the ultimate focus
of nonsmoked cannabinoids. That's been my point all
along."
Do the report's conclusions encourage researchers who
have long sought approval of clinical trials of marijuana?
"I hope so," says the other co-principal investigator, John
A. Benson Jr. "We tried very hard to suggest a number of
experiments ...," adds Benson, who is dean and professor of
medicine emeritus at the Oregon Health Sciences University
School of Medicine.
The report contains six recommendations, each of which
bears on studies of marijuana's effects on humans:
1.Research should continue into the physiological
effects of synthetic and plant-derived cannabinoids and the
natural function of cannabinoids found in the body. The
research should include, but not be restricted to, effects
caused by THC (tetrahydrocannabinol--the best-characterized
cannabinoid in marijuana plants) alone.
2.Clinical trials of cannabinoid drugs for symptom
management should be conducted with the goal of developing
rapid-onset, reliable, and safe delivery systems.
3.Psychological effects of cannabinoids such as anxiety
reduction and sedation, which can influence perceived
medical benefits, should be evaluated in clinical
trials.
4.Studies to define the individual health risks of
smoking marijuana should be conducted, particularly among
populations in which marijuana use is prevalent.
5.Clinical trials of marijuana use for medical purposes
should be conducted under limited circumstances. They
should involve marijuana use for less than six months in
patients with conditions for which there is reasonable
expectation of efficacy, and should collect data about
efficacy. They should also be approved by institutional
review boards.
6.Short-term use of smoked marijuana (less than six
months) for patients with debilitating symptoms must meet
several conditions, including the failure of all approved
medications to provide relief.
Those recommendations would certainly appear to set the
stage for fresh research projects. However, even
participants in the IOM committee warn that change won't
occur overnight. "It will be a long process," predicts
Billy Martin, a professor of pharmacology and toxicology at
Virginia Commonwealth University and a member of the IOM
panel. Martin warns that proposals for clinical studies of
marijuana's medical effects must still meet tough
criteria.
Researchers' Challenges
Critics of the federal government's approach to medical
marijuana agree that it's difficult to set up studies. But
they blame a government that, they say, opposes the idea
that marijuana can offer medical benefits. "It's still as
hard as ever to get marijuana for clinical studies," says
Paul Consroe, a professor of pharmacology and toxicology at
the University of Arizona Health Sciences Center. Consroe
and others complain particularly about the process of
obtaining the starting material for clinical studies.
Scientists can obtain marijuana for such research only from
NIDA, which obtains it in turn from a farm in
Mississippi.(2) NIDA insists that researchers who apply for
the plant must have their studies approved by the National
Institutes of Health. "No other drug of any type has to
meet that standard," says Consroe. "On the one hand, the
government says that we don't have enough proof about
marijuana's medical effects. On the other hand, they won't
let us get the proof."
Consroe and University of Arizona colleagues have
experienced that situation firsthand. In September 1997,
they and the FDA agreed on a protocol for a large,
so-called Phase III study of marijuana's ability to
stimulate the appetites of patients with AIDS and cancer.
Then, in February of last year, recalls Consroe, a new
chair of the FDA committee ordered the group to downsize to
a small, Phase I study. After the team had submitted a new
protocol, the FDA rejected the study entirely. Finally,
"they told us we had to go back to do animal studies," says
Consroe. "I said, 'With all due respect, marijuana has been
studied to death.' It's a political drug. You're not
talking science."
Another disappointed researcher is Ethan Russo, a
neurologist at the Western Montana Clinic. For the past two
years, he has tried to persuade NIH to fund a clinical
study of the use of cannabis in treating migraines. "There
is this singling out of cannabis, which is irrational from
a scientific standpoint," Russo charges. "There does not
seem to be any change in the attitude of NIH top managers
about allowing studies to go forward."
One scientist has managed to cut through the red tape.
Starting in 1992, Donald Abrams of San Francisco General
Hospital sought funding for a clinical study of the
differential effects on AIDS patients of smoked marijuana,
Marinol--a tablet form of THC--and a placebo pill.(3) In
late 1997, he received grant money for the study, which
focuses on patients taking protease inhibitors. "We started
the study last May and have now enrolled 35 patients out of
63," Abrams says. "The project should be complete by next
January." However, his study was not approved until its
focus was changed from the efficacy to the safety of
marijuana.
Lester Grinspoon, a professor of psychiatry at Harvard
Medical School, argues that the safety issue is long dead.
"This country has devoted millions of dollars, mainly
through NIDA, to establish the toxicity of marijuana," he
says. "They've come up with a goose egg." He predicts that
pressure from potential patients will eventually force a
change in attitudes.
The Government's Response
Government sources say good research proposals will
receive a fair hearing. "NIH gets a huge number of grant
applications every year," says Bobbi Bennett, NIH's
spokesperson on medical marijuana. "Usually, we're only
able to fund ... 30 percent of them. We remain open to any
grant applications for research on marijuana. They will be
put through the same peer review system" as other
applications.
ONDCP, meanwhile, has taken a cool view of the IOM
report. "We will continue to rely on the professional
judgment of the Secretary of Health and Human Services, the
director of the National Institutes of Health, and the
Surgeon General on all issues related to the medical value
of marijuana and its constituent cannabinoids," the agency
declared in a statement. "We look forward to considered
responses from our nation's public health officials to the
interim solutions recommended by the report."
Peter Gwynne (pgwynne767@aol.com) is a freelance
science writer based in Marstons Mills, Mass.
References
1.Institute of Medicine, Marijuana and Medicine:
Assessing the Science Base, Washington, D.C., National
Academy Press, 1999.
2.P. Gwynne, "Trials of marijuana's medical potential
languish as government just says no," The Scientist,
9[23]:1, Nov. 27, 1995.
3.P. Gwynne, "Medical marijuana debate moving toward
closure," The Scientist, 11[7]:1, March 31, 1997.
The Scientist, Vol:13, #10, p. 1, May 10, 1999
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