POT'S VALUE AS MEDICINE STILL HAZY

People hearing Jody Corey-Bloom's plan to study how smoking marijuana
affects patients stiffened by multiple sclerosis often can't resist
teasing the doctor.

"Oh, nice research to be in," they say with a mischievous smile.

At the same time, many are curious about the possible medicinal value
of the plant called cannabis sativa. Because for all the stories
about how marijuana cures ills, rigorous scientific studies of its
therapeutic effects are scarce.

The absence of ample data is due largely to the difficulty of legally
obtaining marijuana for medical research. The federal government for
20 years has grown cannabis to research the drug's potential for
abuse and addiction; it was not until 1999 that it established a
policy for making marijuana available to independent researchers
interested in testing for medicinal effects.

"The research has not been easy to do," said Dr. Donald Abrams,
director of the AIDS program at San Francisco General Hospital. "I
mean, you're dealing with a controlled substance that has a lot of
emotional overlay. There are a lot of regulatory issues."

Those regulatory issues have made for a Catch-22: The federal
Controlled Substances Act does not recognize a medical benefit to
marijuana, and its status under that law as a "Schedule I" controlled
substance makes it difficult to obtain for medical research.

The conundrum was highlighted last week in a U.S. Supreme Court
ruling that the Oakland Cannabis Buyers' Cooperative, in distributing
marijuana for medical use, was not exempt from prosecution under
federal drug laws.

"It is clear from the text of the Act that Congress determined that
marijuana has no medical benefits worthy of an exception granted to
other drugs," Justice Clarence Thomas wrote for the unanimous court.

The one legal use of the drug, the court noted, is for
government-approved research projects. But getting that approval is
extremely complicated.

Abrams tried and failed for five years to obtain marijuana legally
before gaining the support of the National Institute on Drug Abuse,
which is in charge of the federally grown crop.

After rewriting his proposal a third time, Abrams in 1997 received
from NIDA $1 million and the marijuana necessary to compare the
safety for AIDS patients of smoking pot vs. ingesting Marinol, a
capsule form of THC, the foremost psychoactive ingredient in
marijuana. Some AIDS patients smoke the drug to stimulate appetite
and help them maintain their weight.

That was the first study to be done with human HIV patients and
smoked marijuana. Abrams said he found that neither the cigarettes
nor Marinol appeared to further degrade the immune system. Moreover,
the patients ate more and gained weight with both forms of the drug.

Abrams is set now to begin another cannabis study, this one focused
on whether the drug would alleviate nerve pain in AIDS patients. This
time, Abrams need not worry about the logistics of obtaining
marijuana because someone else is doing it on his behalf.

Abrams, Corey-Bloom and two other scientists are the first to have
research proposals approved by the new California Center for
Medicinal Cannabis Research. Unique in this country, the center was
established by a 1999 state law with $3 million in funding.

The first batch of studies still are awaiting the final go-ahead. The
research center had to submit the proposals for review and approval
by a state research advisory panel, a scientific review committee at
the U.S. Department of Health and Human Services, the National
Institute on Drug Abuse, the U.S. Food and Drug Administration, and
the federal Drug Enforcement Administration. Once a DEA license is
secured, said center co-director Drew Mattison, the center will place
an order for marijuana with NIDA, which grows pot on one acre of land
near the University of Mississippi. All the sites where the marijuana
will be used must be inspected by NIDA.

The process "is very, very complex," Mattison said. "It has been
very, very detail-oriented, and also new territory for some of these
regulatory agencies. You have to kind of develop policy as they go
along."

Exploring the therapeutic effects of nicotine is much easier, even
though, according to addiction expert Avram Goldstein of Stanford
University, nicotine is far more addictive than marijuana.

Goldstein said advocates of legalizing marijuana share responsibility
for impeding scientific research. "I have been involved in looking at
some of those proposed studies, and there's just an awful lot of junk
science there (from) people who have a bias in favor of smoking
marijuana," he said.

Much of the impetus for research has come from patients and the
public. In 1996, a majority of California voters approved the use of
marijuana as an alternative treatment for certain medical conditions.

For years, doctors had been hearing from seriously ill patients how
smoking marijuana provided relief where other medications failed.

One such patient was Steve Kubby. A former Libertarian candidate for
governor, Kubby and his wife, Michele, were prosecuted last year in
Placer County for growing marijuana in their home. Kubby has a rare
form of adrenal cancer that typically kills. But he has survived
seemingly miraculously for more than 16 years, and his physician, Dr.
Vincent DeQuattro of the University of Southern California, testified
that marijuana appeared to be the reason.

DeQuattro, who was traveling last week, this week, said in an
interview by e-mail that Kubby turned to marijuana after the
conventional medications DeQuattro prescribed made him sick. "I did
testify that since he could not take conventional medications, I
approved of his continuing that therapy," DeQuattro said. "He has
harbored this tumor with equanimity for ... years.

The marijuana-related counts against the Kubbys ultimately were dismissed.

Spurred by medical marijuana laws in several states, the National
Institutes of Health in 1997 appointed an expert panel to review the
scientific literature on marijuana as therapy. The panel concluded
from the information -- much of it anecdotal or based on animal
studies -- that evidence was compelling enough to merit further
research in five areas: appetite stimulation; nausea and vomiting
associated with cancer treatment; neurological and movement
disorders; pain; and glaucoma. That report helped prompt NIDA to make
its pot available to independent researchers.

One area in which considerable data exists on humans is in the use of
cannabis to ease nausea. However, the panel observed, most of the
clinical trials used dronabinol (the generic name for Marinol), the
THC capsule approved in the mid-1980s for use by cancer patients on
chemotherapy.

The problem with dronabinol is that its effects don't necessarily
follow those of smoked marijuana. The plant contains more than 400
chemicals, about 60 of which are psychoactive ingredients called
cannabinoids. THC is only one, albeit the most abundant.

THC capsules also take hours to work, whereas smoked marijuana has
effects within minutes. Moreover, experienced smokers are able to
regulate their doses by controlling their "puff rate" and the depth
of their breath -- possibly delivering enough drug to ease their
symptoms without becoming dysfunctionally "high."

At the same time, smoking carries its own risks, including irritation
of the respiratory system.

Mattison, co-director of the California cannabis research center,
said the center is working with a pharmaceutical company to develop
an under-the-tongue spray. Researchers elsewhere are trying to
develop inhalers and a skin patch.

The flowering tops and leaves of the hearty weed cannabis sativa seem
to have been as medicine for centuries. In 1993, researcher Raphael
Mechoulam of Hebrew University in Jerusalem reported recovering tiny
amounts of THC from a 1,600-year-old family tomb, near the corpse of
a young woman who evidently died in childbirth.

It was Mechoulam who in 1964 isolated THC from marijuana, spurring
the interest of scientists around the world on cannabinoids, which
are found in no other plant. Today, researchers know of two natural
cannabinoids in the human body, and have identified cannabinoid
receptors in the brain and immune system. Their function is, at this
point, unclear.

Growing understanding of the role of natural cannabinoids will be
critical to understanding marijuana's effects on the body, for better
and for worse. But to fully exploit the beneficial effects the plant
may confer will require experiments using the drug and human
subjects. Aside from the difficulty in obtaining legal marijuana,
said Corey-Bloom, it's tough designing a bullet-proof study.

"If somebody's not blinded (to whether they're receiving the drug or
a placebo), then I think that it's very easy for them to report that
(their condition) is improved in one situation and not in another,"
said Corey-Bloom, who directs the multiple sclerosis clinic at the
University of California, San Diego, and proposes to study marijuana
and spasticity, or stiffness.

"I think it's important to separate out the euphoria from real
medicinal benefits. We're not necessarily against someone feeling
good who has a chronic illness," she added, "but I think it's
important to say it didn't have an effect on spasticity, but in fact
they felt better."

When the Supreme Court decision on medical marijuana came out last
week, Corey-Bloom paid close attention, and found she basically
agreed.

"We need to get some good data," she said. "I thought it really
suggested that our work was more timely than ever."