2:00 a.m. March 2, 2002 PST
By Tania Hershman
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."
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