editorial comment Indeed, it is better to stick to Vioxx. It does kill pain forever!

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.


By DAN HURLEY

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