MEDICAL MARIJUANA ON TRIAL

There Seems To Be No Clear Cut Evidence That Medicinal
Marijuana Provides Any Benefits

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, (http://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.