RESEARCHERS AIM TO DEVELOP MARIJUANA WITHOUT THE HIGH

After 10 years of searching, University of Mississippi Professor Mahmoud El
Sohly thinks he has a new way to quiet opponents of marijuana as medicine:
a pot suppository. Designed to ease post-chemotherapy nausea, among other
conditions, its best feature may be what it doesn't do. "There is no high,"
says Dr. El Sohly.

Whether the Food and Drug Administration ever will approve his drug, which
he has tried out on animals and human subjects, is hard to predict, pending
clinical trials sure to cost millions he doesn't yet have. He's trying to
interest drug companies.

For patients turning to marijuana for relief from a symptom such as nausea,
the high may be an unwanted side effect. To the government, it's illegal
substance abuse. So in labs around the world, researchers like Dr. El Sohly
are attempting to create marijuana pills, aerosols, injections and sprays
that don't create a buzz. Some are tweaking molecules, while others are in
the greenhouse crossbreeding plants.

One And The Same

What makes the task so tricky is that the same ingredient that appeals to
pot smokers -- tetrahydrocannabinol, or THC -- is what holds promise as a
medicine. Of the 400 or so chemicals found in the hemp plant, more than 60
are so-called cannabinoids, and none is more psychoactive than THC.

Some challengers in the race are already claiming victory. A tiny New York
City firm called Atlantic Technology Ventures Inc. is waiting to unveil a
synthetic compound called CT-3 -- claimed to be THC without the high.
Sumner Burstein, a professor at the University of Massachusetts department
of biochemistry and molecular pharmacology, developed the drug as a
pain-reliever and says it is nonpsychoactive: "I took one myself -- no
mental aberrations." At least four years of testing await the drug, which
the company hopes to market one day as a "super-Tylenol."

Prof. Audra Stinchcomb of the Albany College of Pharmacy in New York is
testing in the lab a patch designed to relieve the side effects of
chemotherapy in cancer patients. Key to this effort's success is the rate
of "transdermal" intake of the drug -- too little and patients feel no
effect; too much and they get giggly. She attaches synthetic-THC patches to
pieces of skin left over from plastic surgeries to evaluate absorption.

Fifteen Tons

In southern England, three-year-old GW Pharmaceuticals is hybridizing
cannabis plants to breed out psychoactive agents in some cases, to increase
THC in others. The company, which has a unique license from the government
of the United Kingdom, grows 50,000 plants, producing 15 tons of marijuana
a year for medical research. "We have a perfect factory growing one
cannabinoid or another," says founder and chairman Geoffrey Guy.

While most other research involves extracting a single THC molecule from
cannabis and modifying it, Dr. Guy hopes to use the pharmaceutical extracts
of the entire plant. One way to reduce psychotropic effects, says Dr. Guy,
would be to increase the content of other helpful cannabanoids besides THC,
such as cannabidiol, or CBD, which seems to minimize the high.

GW's first product, which could hit U.K. markets as a pain-reliever by
2003: a device the size of a mobile phone that allows a daily dose of a
prescribed number of squirts under the tongue of cannabis extract,
containing both CBD and THC. The dispenser won't allow extra squirts. "We
have chaps [in tests] using heavy machinery ... some are teaching," says
Dr. Guy. "They aren't sitting in a corner high as a kite."

At London's Imperial College, researchers are testing a THC-based drug that
circumvents the brain entirely -- delivered by a spinal injection. Though
it is too early for human trials, researchers are hoping to find that THC
derivatives are more effective than morphine for relieving pain from
spinal-cord injuries.

Individual scientists, academic labs and small drug firms are pushing the
research hardest, largely because big drug companies have traditionally
been leery of the cost and political problems associated with marketing
marijuana as medicine. Also, because cannabis is a natural product in the
public domain, it can't be patented. Today, the only prescription-based
medical marijuana available in the U.S. is Marinol, a synthetic cousin of
THC sold and marketed by Unimed Pharmaceuticals Inc. Though approved as a
nausea drug in 1985, and as an appetite-stimulant for AIDS patients in
1992, it can induce a drug high. Sales today reach an estimated $20 million
annually.

Big companies are starting to get interested in the field. "We see them --
Pfizer, GlaxoSmithKline, Novartis -- all the time at the meetings of the
society now," says Roger Pertwee, a professor at the University of Aberdeen
in the U.K. and secretary of the International Cannabinoid Research
Society, a group of medical and academic researchers. "They never came in
the past." Spokesmen for all three companies said they wouldn't dispute
that assertion but also wouldn't confirm that they have had people at
meetings. Kate Robins of Pfizer Inc. said, "Our job is to cure diseases. We
have 12,000 researchers. We leave no stone unturned."

In 1999, the Institute of Medicine, a branch of the National Academy of
Sciences, made the strongest case to date for cannabis as a potentially
effective treatment for nausea, AIDS-related appetite loss, glaucoma,
multiple sclerosis and other ailments. Its compilation of studies,
"Marijuana and Medicine: Assessing the Science Base," concluded that
cannabinoids have "potentially far-reaching therapeutic applications."

Recent findings suggest that THC holds more potential as a painkiller than
anyone ever guessed. Discoveries that the body produces its own
cannabinoids that bind with receptors located in the brain and elsewhere
lead scientists to believe THC could affect nerve impulses between cells in
precise ways.

"In war, some men lose limbs and they don't feel pain because the body can
turn pain off," explains J. Michael Walker, a professor at Brown University
and current president of the cannabis research society. New research
suggests that "when you activate parts of the brain that turn pain off, it
causes the release of cannabinoids. Can cannabinoids suppress pain
pathways? It's a very exciting science question."

Some scientists remain skeptical. "Anecdote is not evidence," declares Alan
I. Leshner, director of the National Institute on Drug Abuse, which funds
research on addiction. "There is still very little controlled clinical
research on cannabis that demonstrates medical benefit."

Prof. Burstein, of the University of Massachusetts, says other professors
often "get a big grin on their face" when he speaks about his marijuana
research.

"They ask, 'Did you remember to bring the brownies?'"