MEDICAL MARIJUANA ON TRIAL

Medical marijuana is now legal in 11 states, and bills to legalize it are
pending in at least 7 more. The drug is also at the heart of a case being
considered by the United States Supreme Court.

Yet there remains much confusion over whether marijuana in fact has any
significant medical effect.

"People subjectively report benefits," said Dr. Joseph I. Sirven, an
epilepsy specialist and associate professor of neurology at the Mayo Clinic
College of Medicine in Scottsdale, Ariz. "There's a whole Internet
literature suggesting what a wonderful thing it is. But the reality is, we
don't know."

In an editorial last year in the journal Neurology, Dr. Sirven pointed out
that the best studies of marijuana's effects on humans have so far shown
little objective evidence of benefit in patients with epilepsy or multiple
sclerosis. And a growing body of research indicates that, at least in
teenagers, heavy marijuana use over a period of years significantly
increases the risk of developing psychosis and schizophrenia.

In the Supreme Court case, two California residents, Angel McClary Raich
and Diane Monson, brought a suit against federal officials in October 2002
to defend their use of marijuana after six of Ms. Monson's marijuana plants
were seized and destroyed by the Drug Enforcement Administration.

The federal government, which considers marijuana illegal under the
Controlled Substances Act, asked the Supreme Court to overturn a Court of
Appeals ruling that supported the two women. Oral arguments were heard just
after Thanksgiving, and a ruling could come any day.

Ms. Raich's physician, Dr. Frank Henry Lucido of Berkeley, Calif., asserted
in an affidavit that Ms. Raich risked death if she was denied the marijuana
to treat nausea, anorexia, severe chronic pain and other disorders brought
on by a variety of illnesses, including post-traumatic stress disorder,
asthma and an inoperable brain tumor. On a Web site created on her behalf,
www.angeljustice.org, Ms. Raich says she joined the lawsuit "in order to
save my life."

While little scientific evidence supports such a lifesaving role for
marijuana, many studies have found modest benefits in patients' subjective
measures of pain, sleep, nausea, appetite, tremors and muscle spasms.

"There's nothing better for nerve pain than marijuana," said Phillip Alden,
41, a writer in Redwood City, Calif.

Twice a month, he spends about $200 to buy a half ounce of high-potency
marijuana from one of San Francisco's medical marijuana buyers' clubs.

He smokes it three or more times a day to treat pain from a back injury,
and to improve his appetite and reduce nausea associated with AIDS and the
antiviral drugs he takes for it. It has even checked the progression of his
peripheral neuropathy, he said.

Two recent surveys, also published in Neurology, have documented widespread
use of marijuana among Canadian patients and a widespread belief in its
benefits.

The first survey, of 220 patients with multiple sclerosis, found that 36
percent had used marijuana to treat their symptoms, and that 14 percent
were using it at the time of the survey.

The second survey, of 136 patients attending the University of Alberta
Epilepsy Clinic, found that 21 percent had used marijuana in the previous
year. Just over two-thirds of the active users said it decreased the
severity of their seizures and slightly more than half reported a decreased
frequency of seizures.

But the lead author of the epilepsy study said it proved only that some
patients believed in marijuana, not that it or its active ingredients,
called cannabinoids, actually worked.

"There's not been a randomized, controlled trial demonstrating that
marijuana or any cannabinoid is any more effective in controlled seizures
than a placebo," said Dr. Donald W. Gross, director of the University of
Alberta's adult epilepsy program.

Although doctors may now prescribe marijuana in Canada for certain
disorders, including epilepsy, Dr. Gross said he had never done so. "It's
terribly complicated from a physician's standpoint, and somewhat
frustrating," he said. "We have a product that has been legitimized without
any evidence of efficacy."

A large body of research in test tubes and animals supports the view that
cannabinoids have anticonvulsive properties. But while a 2003 study of 657
patients with M.S. published in the journal Lancet found significant
improvements in subjective reports of muscle spasms and pain, it found no
improvement by objective measures after 15 weeks.

A follow-up report on the same group of patients did show modest benefit
after 12 months, but the researchers said that the results should be
interpreted cautiously, because the study had been intended to test only
short-term benefits.

Dr. David Baker, a professor at the Institute of Neurology in London, has
found beneficial effects of cannabinoids in mice who have an artificially
induced type of multiple sclerosis. But, he said, "Showing clinical benefit
in humans has been an elusive beast."

"At best there is a narrow therapeutic effect before the side effects
become unacceptable for many people," he said. " What is clear is that
there have been no dramatic improvements overall."

Dr. Kenneth P. Mackie, a professor of anesthesiology at the University of
Washington, has devoted 15 years to studying the brain's response to
cannabinoids through specialized brain receptors called CB1 and CB2.

"There's a whole bunch of theoretical reasons suggesting there would be a
benefit for marijuana on a variety of conditions relating to pain and
neuroinflammation," Dr. Mackie said. "But the clinical studies just aren't
there."

Far stronger evidence exists for a harmful effect of marijuana in teenagers
who use it early and often. "We know that cannabis is a contributory cause
of schizophrenia," said Dr. Robin M. Murray, a professor at the Institute
of Psychiatry in London and the co-editor of a new book, "Marijuana and
Madness: Psychiatry and Neurobiology."

In a 2002 study published in the British medical journal BMJ, Dr. Murray
reported that New Zealand teenagers who started smoking marijuana before
age 15 and continued doing so on a daily basis raised their risk of
developing psychosis and schizophrenia from about 2 percent to as much as
10 percent.

The study, he said, ruled out the possibility that the teenagers who used
marijuana were also those who were more likely to develop schizophrenia,
whether or not they used the drug.

Still, "You have to take a lot to go psychotic," Dr. Murray said. "But with
five joints a day for five years, an amount that is increasingly common in
Europe, you're seriously increasing your risk of schizophrenia."

He added that even so, the risk dropped sharply as people aged, so that
most chronically ill people who used marijuana for medical purposes were
unlikely to experience psychosis as a result.

Research in the United States has been greatly hampered by legal restrictions.

In 1997, Dr. Donald Abrams, an oncologist and assistant director of the
Positive Health Program at the University of California at San Francisco,
became the first doctor authorized by the National Institute of Drug Abuse
to receive marijuana to conduct research to determine if it provided
medical benefits.

Now more than a dozen California researchers are studying it under the
auspices of the University of California's Center for Medicinal Cannabis
Research.

"Cannabis has a 5,000-year history of medical use," Dr. Abrams said. He
said he had completed three studies in patients with H.I.V. that showed no
negative effects on their immune systems or on the functioning of the
protease inhibitor drugs they were taking.

He is now trying to show that marijuana has a beneficial effect on immune
functioning, he said.

The patients were brought into the hospital to smoke marijuana under
medical supervision.