MEDICAL MARIJUANA ON TRIAL

As Supreme Court Nears Decision, Benefits Of Drug Remain In Question

Medical marijuana is now legal in Washington and 10 other states, and bills
to legalize it are pending in at least seven more. The drug is also at the
heart of a case being considered by the U.S. Supreme Court.

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

"People subjectively report benefits," said Dr. Joseph 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."

Diane Ballard is one of those subjective cases. Ballard has been smoking
marijuana since 1999 to help control the pain and nausea caused by
treatments she received for a rare form of cancer.

"When I don't take marijuana I'm nauseous all the time and I can't hold
down any food," said Ballard, who smokes up to two marijuana cigarettes a
day at her home in West Seattle.

Multiple rounds of chemotherapy and radiation left their mark on Ballard's
body. She's been diagnosed with fibromyalgia and severe acid reflux.

Washington voters approved a law in 1998 that allows people with a terminal
or debilitating illness to grow, smoke or obtain marijuana for medical
needs with a doctor's recommendation.

Ballard's doctors -- she sees someone for pain, an oncologist and an
arthritis specialist -- have all provided her with notes suggesting
marijuana will do her more good than harm.

"I'm positive it helps me," said Ballard. "For somebody to say it doesn't
help, they haven't a clue."

Dr. David Baker, a professor at the Institute of Neurology in London, has
found beneficial effects of cannabinoids in mice that 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. What is clear is that there have been no
dramatic improvements overall."

Dr. Kenneth 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," Mackie said. "But the clinical studies just aren't there."

In an editorial last year in the journal Neurology, Sirven said the best
studies of marijuana's effects on humans so far have shown little objective
evidence of benefit in certain patients -- those 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.

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-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," Abrams said.

He said he had completed three studies in patients with HIV 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.

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 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.

Raich's physician, Dr. Frank Henry Lucido of Berkeley, Calif., asserted in
an affidavit that 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, 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 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, 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 Gross, director of the University of
Alberta's adult epilepsy program.

A large body of research in test tubes and animals supports the view that
cannabinoids have anti-convulsive properties. But while a 2003 study of 657
patients with MS 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 the results should be interpreted
cautiously because the study had been intended to test only short-term
benefits.

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 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, 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.

"You have to take a lot to go psychotic," 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."

But he added, 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.