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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.