ANOTHER CANNABIS DRUG SANS BUZZ

Jerusalem -- Hey man, wanna score some cannabinoids? An Israeli
pharmaceutical company is working on a drug mimicking cannabis' chemical
constituents -- cannabinoids -- to offer marijuana's therapeutic benefits
without the buzz.

The new type of synthetic cannabinoid is "equivalent to ... the
best-quality marijuana," says Dr. George Fink, vice president of research
at Pharmos, which presented its new bicyclic dextrocannabinoic compounds at
the BIO CEO and Investor conference in New York in February.

The cannabis plant contains over 60 cannabinoids. When you smoke (or eat)
pot, the cannabinoids bind to two cannabinoid receptors in the body, called
CB1 and CB2. CB1 appears to enhance appetite, reduce pain and ease muscle
spasms -- and it is also the receptor that produces the psychotropic
effects smokers want.

However, getting stoned is not what the pharmaceutical industry wants for
its clients. Pharmos' synthetic cannabinoid shuns CB1 to bind almost
exclusively to CB2. So, unfortunately for some, there's no getting wasted.
"I wouldn't call the 'high' an adverse side effect," Fink says. "The
serious side effects are those which prevent people getting on with their
normal work."

What you get instead is CB2, with its own box of tricks: CB2 is expressed
by immune and inflammatory cells and acts as an anti-inflammatory. "It
shows very good activity in animal models for multiple sclerosis, and also
seems to be a good analgesic for pain ... as well as being effective in
inflammatory bowel diseases," Fink says.

Pharmos' cannabinoids are derivatives of a compound discovered by Hebrew
University of Jerusalem professor Raphael Mechoulam and licensed to the
company.

Mechoulam is a founding father of medicinal marijuana research. In 1964, he
was the first to isolate marijuana's active ingredient, THC. "I am a
chemist working in natural products, and these are important natural
products, the one drug of abuse used most widely in the world," he says.

In 1992, Mechoulam and colleagues identified the first cannabinoid in the
brain and called it anandamide, after the Sanskrit for "internal bliss."
Since then, more have been found. "The cannabinoids in the brain seem to be
very central to the functioning of our body," Mechoulam says.

Dr. Paul Mallet, a behavioral pharmacologist researching cannabinoids at
Australia's University of New England, is interested in Pharmos' new
compounds. Mallet's research is funded by the Australian Research Council.
He also manages the Cannabinoid Science mailing list.

"Other pharmaceutical companies have produced synthetic chemicals that
activate both CB1 and CB2 receptors," he says. "They have also developed
... chemicals that selectively block either CB1 or CB2 receptors. However,
the development by Pharmos of chemicals that selectively stimulate the CB2
type of cannabinoid receptor is an important breakthrough."

The U.S. government is also supporting cannabinoid research. Dr. Steven
Childer of the department of physiology and pharmacology at Wake Forest
University is conducting work on cannabinoids in the brain, for example.
The National Institute on Drug Abuse is funding part of this research.

Childer welcomes Pharmos' specific CB2 cannabinoid, calling it preferable
to natural THC because of its lack of psychotropic effects. But he is
uncertain if such compounds could bring all the therapeutic benefits
cannabis has to offer.

"They probably would not be effective in treating problems originating in
the central nervous system ... treatment of nausea and vomiting associated
with chemotherapy, loss of appetite (for example, in AIDS patients), CNS
motor diseases and certain types of pain," he says.

Pharmos expects to begin Phase I clinical trials in mid-2003, and it could
take another five years before trials and regulatory procedures are completed.

One point stressed by all involved is that the development of
cannabis-based medicines should not be linked to the thorny issue of
legalizing marijuana. Says the Hebrew University's Mechoulam: "The medical
thing should be looked upon separately, whatever anyone thinks about
marijuana. If it is a good medicine, then chances are it will be approved,
with certain legal constraints."