STUDIES ATTEMPT TO GET PAST MEDICAL MARIJUANA MYTHS

SAN DIEGO -- Maybe the smoke is about to clear in the debate over medical
marijuana.

Few ideas, it seems, are so firmly held by the public and so doubted by the
medical profession as the healing powers of pot. But at last, researchers
are tiptoeing into this field, hoping to prove once and for all whether
marijuana really is good medicine.

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," said 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.

Sober Scholarship

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, 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 the pot plant.

"We talked about it a lot," said 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.

Voter Approval

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," said 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 might 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 could be hard to accomplish.

Other studies will compare marijuana as a whole 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.

Prescriptions Unlikely

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," Grant said. "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," said
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,
distorted perception of time and distance, talkativeness and the rest.
Others might 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 said 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 said, 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, said 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. Every year or two, it pays the University of Mississippi to
plant 1 1/2 acres of marijuana for experiments.

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, Steven Gust of the drug institute said the real issue was lack of
interest. "The fact of the matter is, there were very, very few
applications to conduct research on medical applications of marijuana," he
said.

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.

Cannabis Converts

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 National Organization for the Reform of
Marijuana Laws Foundation, which wants to legalize marijuana.

"We're going to have to go through this business of doing these studies,"
he concedes. "But they won't prove anything that clinicians who have paid
attention to this don't already know."