REPORT SEES MEDICAL APPLICATIONS FOR MARIJUANA'S ACTIVE INGREDIENTS

Although Unsafe To Smoke, Chemicals Offer Hope For Pain Relief

Marijuana is too dangerous to the lungs to make smoking "grass" a safe
long-term treatment for illness but some of the active ingredients in the
weed could sprout into a whole new family of medicines.

Those are among the conclusions of a landmark report issued in March by an
expert panel on the medical uses of marijuana, a topic that has pitted
patients and pro-legalization activists against the federal government.

Marijuana's active ingredients belong to a chemical family called the
cannabinoids. In recent years, scientists have found that these chemicals
as well as receptors on cell surfaces that respond to them are found
naturally in the brain, where they probably play a role in memory, control
of movement and pain perception.

Scientific knowledge of cannabinoids has exploded, far outstripping the few
well-conducted medical studies of marijuana's therapeutic effects in
patients, according to the pair of scientists who headed the panel.
Together, the new laboratory findings and the clinical results suggest
that some cannabinoids could be developed into promising drugs for pain
control, the relief of nausea and vomiting, and stimulation of appetite in
people who have lost weight because of AIDS or other diseases.

Some patients currently smoke or eat marijuana to treat those problems, a
situation that has produced conflict between states that want to legalize
medical use of the drug and the federal government, which has opposed any
legalization.

"There are real clinical opportunities" to develop new drugs from
cannabinoids, said Stanley J. Watson, co-director of the Mental Health
Research Institute at the University of Michigan and co-chairman of the
panel that conducted the review for the Institute of Medicine (IOM), an
independent advisory body.

The IOM report had been eagerly awaited by both sides in the ongoing debate
over whether marijuana should be made legally available for people with
certain intractable symptoms, such as nausea caused by chemotherapy or
wasting associated with AIDS.

To the delight of many activists who have urged legalization of medical use
of the drug, the panel concluded that some of marijuana's constituents are
potentially effective therapies. Nevertheless, the report strongly opposes
the use of smoked marijuana except in short-term scientific studies
lasting less than six months, citing the dangers posed by tar, carcinogens
and other substances present in the smoke.

"Numerous studies suggest that marijuana smoke is an important risk factor
in the development of respiratory disease" and is associated with an
increased risk of cancer, lung damage and poor pregnancy outcomes, the
report states.

It calls for the rapid development of an inhaler that could deliver
cannabinoids into the lung from which they are quickly absorbed into the
bloodstream thus allowing patients to obtain the desired effects without
smoking.

"While we see a future in the development of . . . cannabinoid drugs, we see
little future in smoked marijuana as a medicine," said panel co-chairman
John A. Benson, an emeritus professor of medicine at Oregon Health
Sciences University.

How might cannabinoid drugs be used? "Analgesia (pain relief) may be the
biggest market for commercial exploitation," Benson said.

Animal studies show that cannabinoids can relieve mild to moderate pain,
working about as well as codeine. Because they act upon a different set of
brain receptors than the opiates (such as morphine and codeine), they are
unlikely to have the same side effects and might be used in combination with
opiate drugs. The report calls for additional human studies in this area,
saying the few trials conducted in humans so far are inconclusive.

For nausea and vomiting caused by chemotherapy, cannabinoids are mildly
effective, but for most patients, neither marijuana or THC (an active
ingredient of marijuana) works as well as other anti-nausea drugs currently
available, the report found. Those drugs are effective in more than 90% of
patients, Benson said, while THC is
effective only in about 25%. (THC, or dronabinol, sold under the brand name
Marinol, is approved by the Food and Drug Administration for control of
severe nausea in chemotherapy patients who don't respond to other drugs.)

But cannabinoids might enhance control of nausea when combined with other
drugs, the panel concluded, and delivering cannabinoids by inhaler might be
an effective route for people who are already too nauseated to swallow. It
called for further research on the topic.

Although many patients with AIDS say smoking marijuana has improved their
appetite and has helped them regain weight, the first clinical trial of
marijuana in such patients, conducted by Donald Abrams of the University of
California at San Francisco, has not yet been completed. Marinol was
approved by the FDA for this purpose in 1992, but some people with AIDS
find its psychological effects too intense and say it takes too long to
act, the report said.

The panel urged further research on the use of cannabinoids in AIDS, saying
they could be helpful both as appetite stimulants and to reduce pain,
nausea and anxiety.