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Natural Alternative to Medical Marijuana Discovered

Blocked enzyme lets chemical compound in brain ease pain, study finds

THURSDAY, July 26, 2001 (HealthDayNews) -- The controversy over the medical use of marijuana may soon be moot.

California researchers say they have discovered that blocking a particular enzyme, known as FAAH, in mice lets a natural, marijuana-like compound in the brain trigger pain relief.

That compound is called anandamide, and it's a chemical cousin of tetrahydrocannabinol (THC), the cannabinoid found in marijuana. Researchers at the Scripps Research Institute have shown anandamide activity was heightened in mice that lack FAAH, which typically eliminates anandamide from the brain. More importantly, the same mice had less sensitivity to pain, which is a main medical use of marijuana.

The findings appear in the July 31 issue of the Proceedings of the National Academy of Sciences.

"What we would like to do is try to get rid of the enzyme, block it chemically by an inhibitor," says lead author Benjamin F. Cravatt, an assistant professor of cell biology and chemistry at Scripps. "We could increase the (natural) levels of cannabinoids and get a more sensitive effect."

A lot of biochemical research is needed to reach that goal, Cravatt says. Much of that would be devoted to maximizing the benefits of anandamide while minimizing the side effects, which can include short-term memory loss.

"Anandamide reduces pain sensitivity, but it has a lot of side effects," Cravatt says. "We have to see whether those can be separated, one from the other, so we get pain reduction without side effects."

A number of molecules that can inhibit FAAH are available for study, Cravatt says. Work will be needed to identify a specific molecule, but the new report shows "we have a legitimate candidate for a drug target."

The importance of the report is that "it really proves that anandamide is broken down by this enzyme and no other," says Dale Deutsch, an associate professor of biochemistry and cell biology at the State University of New York at Stony Brook. Deutsch, who is president of the International Cannabinoid Research Society, played a major role in research that first described the role of FAAH.

Deutsch is also working with anandamide inhibitors.

"The goal of our research is to understand the mechanism by which anandamide is broken down in the brain, and how cells take it up," he says. "FAAH appears to act like a straw, sucking anandamide into the cell to get rid of it."

A medication that heightens anandamide activity could have a number of uses, Deutsch says. Cannabinoids also affect mood, blood pressure and memory, he explains, and they are closely related to the brain mechanisms of drug addiction, so one possible use would be reducing the ill effects of withdrawal from addiction.

Weight reduction is another possibility, Deutsch says. Safoni, an Italian pharmaceutical company, is planning clinical trials of a compound that blocks cannabinoid receptors in the brain as an aid to weight loss.

What To Do

Detailed information about cannabinoid research is available from the International Cannabinoid Society.

For more on anandamide research, read this article from the Society for Neuroscience.

SOURCES: Interviews with Benjamin F. Cravatt, assistant professor, cell biology and chemistry, Scripps Research Institute, La Jolla, Calif; Dale Deutsch, associate professor, biochemistry and cell biology, State University of New York, Stony Brook; July 31, 2001, Proceedings of the National Academy of Sciences
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