Pot debate comes to a boiling point

To believers, marijuana's benefits are already beyond discussion: Pot eases pain, settles the stomach, builds weight and steadies spastic muscles. And that's hardly the beginning. They speak of relief from PMS, glaucoma, itching, insomnia, arthritis, depression, childbirth, attention deficit disorder and ringing in the ears.

Marijuana is a powerful and needed medicine, they say, tragically withheld by misplaced phobia about drug addiction.

However, the drive to legalize medical marijuana is based almost entirely on the testimonials of sick people who swear it makes them feel better. Those stories are not the kind of dispassionate experimentation that drives medical thinking.

"We lack evidence that there is something unique about marijuana, other than an impressive number of anecdotal reports," says Dr. Billy Martin, chief of pharmacology at the Medical College of Virginia.

In the medical establishment's view, the buzz about marijuana is little more than that.

Pot has many effects on the body, including some that are probably worthwhile. But does it substantially relieve human suffering, they ask? And if so, is it any better than medicines already in drugstores?

For the first time in at least two decades, marijuana the medicine is being put to the test. Scientists say they will try to hold marijuana to the same standards as any other drug, to settle whether its benefits match its mystique.

Given marijuana's recreational uses and abuses, people in this new field are understandably eager to come across as serious scientists experimenting with a serious medicine. (Even marijuana's usual reason to be -- the high -- is dismissed as a mere side effect, and probably an unwanted one at that.)

One way to buff up a pharmaceutical's raffish image -- especially one that's a drug in more than one sense of the word -- is to call it something else. When the University of California at San Diego started the country's first institute to study the medical uses of marijuana this year, they named it the Center for Medicinal Cannabis Research. Cannabis is the botanical term for pot.

"We talked about it a lot," says Dr. Igor Grant, the psychiatrist who heads the new center. "Marijuana is such a polarizing name. We don't want this institute to be caught in the cross fire between proponents and antagonists. Ultimately, if cannabis drugs become medicine, they will almost certainly be known by that name, not marijuana."

The center will give out $9 million over the next three years to California researchers -- enough to underwrite six or seven marijuana studies a year each involving between 20 and 50 patients.

At least four other studies of the medical effects of marijuana are planned. Three are sponsored by the National Institutes of Health, the other by California's San Mateo County.

The medical marijuana movement began in earnest in 1996, when California passed a statewide referendum intended to make it legal. Alaska, Arizona, Hawaii, Maine, Oregon and Washington adopted similar laws, and Colorado and Nevada joined them in the November election.

"I was just so surprised at these policy decisions being made with so little scientific information," says Margaret Haney of Columbia University. "I'm not against the use of medical marijuana. There's just no data about its efficacy."

Most of the new research will probably focus on four main uses of marijuana that seem to hold the greatest promise:

--Relieving severe nausea and vomiting caused by cancer chemotherapy. This is probably marijuana's best-known medical use. While the drug almost certainly helps ease nausea, there is no research showing how it stacks up against highly effective anti-nausea drugs developed over the past 15 years.

--Stopping weight loss. Marijuana clearly improves appetite. However, the drug has not been adequately tested in people who are unintentionally losing weight, such as those with AIDS or cancer.

--Treating muscle spasticity conditions, including multiple sclerosis. Many victims say it helps, and some animal research backs up the idea. But is it better than standard medicines?

--Easing pain. Researchers especially want to test it on AIDS patients with peripheral neuropathy, numbness and pain in the feet that afflicts between 20 percent and 30 percent with the disease. Animal studies suggest marijuana may be a mild to moderate painkiller, and many with AIDS are already using it, since there is no other good treatment.

One of the first questions to answer is whether objectively testing marijuana as a medicine is even practical. At the San Mateo County Health Center, Dr. Dennis Israelski will tackle this by enrolling 60 AIDS patients who already use marijuana for painful neuropathy.

They will be randomly assigned to smoke marijuana -- or forgo it -- for six weeks. Will people go along with this if it means giving up something they already believe helps them? If not, larger, more elaborate studies of marijuana may be hard to accomplish.

Other studies will compare marijuana to THC -- delta-9-tetrahydrocannabinol -- the most active ingredient in pot.

THC has been available since the 1980s in a synthetic pill form called Marinol.

Theoretically, THC and smoked marijuana should do pretty much the same things, although some argue that the other chemicals in pot are essential for its effects. But many prefer smoking marijuana because the dose is much easier to control.

Marinol takes a couple of hours to kick in. By then it's impossible to fine tune the level in the bloodstream, which sometimes is too high, producing an unpleasantly intense and uncontrollable high.

The joint is an efficient drug delivery system. When smoked, marijuana's chemicals reach the bloodstream in seconds and hit the brain soon thereafter. Users can regulate the effect puff by puff.

In one of the new studies, Haney will compare marijuana with Marinol in AIDS patients experiencing unwanted weight loss. Volunteers won't be told whether they are getting genuine marijuana or dummy joints, Marinol or sugar pills. Then she'll see who eats the most.

But even if Haney and others show marijuana is a uniquely useful medicine, many doubt that packs of marijuana cigarettes will ever become standard items at the pharmacy.

The job of making marijuana an official prescription medicine would be daunting. Because the stuff cannot be patented, no drug company will pay hundreds of millions for the encyclopedic testing necessary to convince regulators.

And then there is that drug delivery system. Nonsmokers often have trouble inhaling marijuana smoke, which they find harsh. And it is, after all, a form of smoking, one of the ultimate health taboos.

"It's not going to be easy to sell marijuana cigarettes as a medicine, even if it could be shown there are particular benefits," says Grant. "It seems that if these things are indeed useful, we would have to find a way to deliver them in a manner that is prescribable."

To many, that means marijuana's real future is its ingredients, THC and the other 60 or so unique compounds called cannabinoids. These are chemicals that pharmaceutical firms can isolate, improve and call their own. These products could offer the health benefits of marijuana, only better, refashioned to avoid pot's unwanted effects and delivered, of course, without smoke.

"Marijuana does too many things to be a really good drug by itself," says John Huffman of Clemson University, a chemist who works with cannabinoids full time.

Some of the things it does are obvious to the 70 million or so Americans who admit trying marijuana: the sense of well-being, a ravenous appetite, messed-up perception of time and distance, talkativeness and the rest. Others may be less so. Marijuana also appears to disrupt short-term memory and suppress immune defenses.

Among the companies searching for better ways to harness marijuana are Unimed Pharmaceutics of Deerfield, Ill., which makes Marinol. The company is working on a THC aerosol spray, intended to offer the quick, easily controllable wallop of marijuana smoking.

Unimed President Robert E. Dudley says that in testing so far, the spray seems to work pretty much like a joint, reaching peak blood levels of THC within minutes. "It mirrors what you would expect to see with inhaled marijuana smoke," he says, including the high.

The high, in fact, is one thing that some pharmaceutical designers would like to get rid of.

Atlantic Technology Ventures of New York City is testing a synthetic form of THC intended to be a painkiller. By tweaking the molecule, says CEO Joseph Rudnick, "we kept most of the benefits of THC but got rid of the psychogenic effects." In safety testing in France, no one got high.

All of the research done on genuine marijuana will use pot supplied by the nation's only legal supplier, the federal government's National Institute on Drug Abuse. Until recently, all of it went to experiments intended to document marijuana's hazards, not its benefits. Some complain that the government provided pot only for government-financed research and made that funding almost impossibly difficult to get. However, Dr. Steven Gust of the drug institute says the real issue was lack of interest. Now, the government will supply marijuana for scientifically rigorous studies backed by nongovernment organizations. It is even shipping some north for experiments sponsored by Health Canada, the Canadian government agency.

To the believers, however, all of this is simply an attempt to prove the obvious, and they question whether the studies are necessary at all.

Dr. Lester Grinspoon, a retired Harvard psychiatrist, became a believer in the 1960s. His son suffered terrible nausea during treatment for leukemia and tried marijuana against his father's advice. It seemed to work. Instead of vomiting for eight hours after chemotherapy, he'd ask to stop for a sandwich on his way home. Now Grinspoon is chairman of the NORML Foundation, which wants to legalize marijuana.

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