IS MARIJUANA REALLY MEDICINE? AT LAST IT'S BEING PUT TO THE TEST

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,'' 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. Every year or two, it pays the University of
Mississippi to plant an acre and a half 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, Dr. Steven Gust of the drug institute says 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 says.

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.

``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.''