ENZYME COULD LEAD TO MEDICAL MARIJUANA ALTERNATIVE

NEW YORK (Reuters Health) - In findings that could one day offer an
alternative to so-called medical marijuana, scientists have discovered that
blocking a particular enzyme in mice allows a natural marijuana-like
compound in the brain to trigger pain-numbing effects comparable to the drug's.

Researchers have known that the brain chemical anandamide acts on the same
brain receptors as marijuana does. Anandamide is known as an endogenous
cannabinoid, a class of marijuana-like compounds that naturally exist in
the body.

What has been unclear is why injecting anandamide into the body does not
have the same medicinal effects that marijuana reportedly has.

"It can't accumulate and hang around like THC (marijuana's active
ingredient)," Benjamin F. Cravatt of The Scripps Research Institute in La
Jolla, California, explained in an interview.

Cravatt and his colleagues hypothesized that an enzyme called FAAH--for
fatty acid amide hydrolase--quickly breaks down extra anandamide in the
brain before it can trigger marijuana-like effects. They confirmed this
belief in experiments with mice engineered to lack the FAAH enzyme.

When these FAAH-less animals were exposed to various doses of anandamide,
they showed effects similar to those that have been seen in mice treated
with THC, Cravatt explained. For one, the mice became lazy and less
responsive. More importantly, they became less sensitive to pain, according
to the report in the July 31st issue of the Proceedings of the National
Academy of Sciences.

These findings, Cravatt said, hold out the possibility that a drug that
blocks the FAAH enzyme in humans will allow the natural anandamide system
to work as a painkiller--but without making patients inhale the toxic
compounds in marijuana smoke or experience the drug's mind-altering effects.

He noted that he and his colleagues will also look at whether mice lacking
the FAAH enzyme show changed eating patterns. Advocates of medical
marijuana use say that in addition to easing the chronic pain of cancer and
other conditions, the drug helps prevent AIDS-linked wasting by stimulating
patients' appetites.

A drug that blocks FAAH in the brain would likely be more desirable than
either marijuana smoking or the synthetic cannabinoids now available for
chronic pain control, Cravatt suggested. It would get around the ill
effects of smoking and probably be more effective than introducing a
foreign cannabinoid because it would boost the body's natural cannabinoid
system.

"Ideally," Cravatt said, "what you want is to allow the endogenous system
to be enhanced."

SOURCE: Proceedings of the National Academy of Sciences 2001;98:9371