Appetite regulator. Molecules in the brain that act like the active ingredient in marijuana spur mice to eat.

Making Sense of the Munchies

Bill Clinton may not know it first hand, but millions of marijuana smokers who have inhaled claim that cannabis boosts their appetite. Now, new results show how the brain's own cannabis-like compounds can lead to late-night refrigerator raids. The results may lead to new drugs to control obesity or boost the appetite of anorexics and cancer patients treated with chemotherapy.

Appetite is regulated by more than a half dozen molecular signals, all working together in ways that still are not well understood. Cannabis boosts appetite in rats and mice; because the brain makes its own cannabis-like molecules, called cannabinoids, pharmacologist George Kunos of the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, and his colleagues asked if cannabinoids help regulate appetite.

The hunch was right, the researchers report in the 12 April issue of Nature. Genetically engineered mice whose brains lacked a receptor needed to sense cannabinoids didn't have healthy appetites: They ate about 40% less, on average, than normal mice. And a drug that blocked the action of cannabinoids led normal mice to eat only as much as the mutant animals.

The cannabinoids seem to be a key part of the neural circuit that regulates appetite, Kunos says. Obese mice and rats that can't make leptin, an important appetite-regulating hormone, showed higher levels of two cannabinoids in the hypothalamus, a brain region where leptin is thought to act. Kunos says that drugs that block or boost cannabinoid signaling could alter people's appetite.

"I think it's very exciting work ... that reveals an unexpected connection [between leptin] and endogenous cannabinoids," says pharmacologist Daniele Piomelli of the University of California, Irvine. And he and other researchers say that while hurdles still remain, the findings boost hopes that a cannabinoid-blocking drug could be used to treat obesity.

Related sites

The International Cannabinoid Research Society
An overview of the cannabinoid system in humans