HIGH HOPES

Can You Get The Benefits Of Cannabis Without The Drag?

The painkilling effect of cannabis can be reproduced by boosting the effect
of the body's own cannabis-like chemicals, according to American
scientists. The finding raises the prospect of painkillers that do the same
trick as smoking a joint but without any of the side effects.

The active ingredient of marijuana, called tetrahydrocannabinol, has a
variety of effects. It reduces pain, lowers body temperature and enhances
appetite. It achieves these effects by binding to cells in the brain called
cannabinoid receptors.

However, the medicinal use of marijuana is highly controversial, and even
some of the drug's advocates admit that its action is less specific than
doctors would like. Harnessing the pain relief without the psychoactive
effects of the drug would be useful, says Benjamin Cravatt of the Scripps
Research Institute in La Jolla, California. But cannabinoid receptors are
widespread in the brain and the immune system, so it hasn't been possible
to separate the desired effects of THC from the others.

Now Cravatt's team, together with Billy Martin and Aron Lichtman of
Virginia Commonwealth University in Richmond have stumbled across a novel
strategy. This strategy relies on harnessing the body's own supply of
cannabinoid-like compounds, such as anandamide.

The researchers were studying genetically engineered mice with a
switched-off gene that would normally code for a protein called fatty acid
amide hydrolase. Because FAAH's job is to break down anandamide, the mice
had an excess of the chemical.

Apart from this disrupted gene the mice were normal. "These animals were
not cataleptic or wasted," says Cravatt. But they did have a higher pain
threshold. For example, the modified mice licked wounded areas less than
half as often as controls. This suggests that drugs that inhibit FAAH could
be powerful painkillers with few side effects. The painkilling effect
completely disappeared when the mice were injected with a drug that clogs
the receptors, proving that the pain relief used the same pathway as THC.

"It's an outstanding result," says George Kunos of the National Institutes
of Health near Washington DC, who studies the effects of endogenous
cannabinoids. "These mice are going to be a major breakthrough in
understanding how cannabinoids work."

Why the modification has such a specific effect on pain isn't clear, but
Cravatt believes that anandamide is released in the brain in response to
pain. If he's right, FAAH inhibitors could be of great therapeutic value.
"We might be able to let the body produce anandamide exactly where it's
needed," says Cravatt. "By simply blocking its degradation we'll get a more
robust effect," he says.

More at: Proceedings of the National Academy of Sciences (vol 98, p 9371)