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April 11, 2001 -- Those who try marijuana (and inhale) know that smoking it can bring on an acute snack attack known as "the munchies." Scientists from Italy, the U.S. and Japan now say that pot may stimulate the appetite by interacting in the brain with a key hunger-controlling hormone.

The discovery suggests that in mice and probably in humans, the appetite-regulating hormone leptin, which is produced by fat cells, may suppress hunger by controlling brain levels of cannabinoids, naturally occurring substances that are also found in marijuana.

The research also indicates that cannabinoids and other substances controlled by leptin may contribute to overeating in some people who are obese, say George Kunos, PhD and colleagues in the April 10 issue of the journal Nature.

"The potential therapeutic implications are obvious, and that is that in obesity, where reducing food intake and appetite is a primary goal, one could think of blocking [a cannabinoid docking-site in the brain] as one means to achieve that," says Kunos, scientific director at the National Institute on Alcohol Abuse and Alcoholism.

Researchers have long known that cannabinoids stimulate appetite. In fact, doctors use a cannabinoid chemical derived from marijuana, called THC, to help maintain appetite and weight in people with advanced AIDS and other body-wasting diseases.

Leptin is a hormone produced by fat cells that has been shown to both reduce food intake and increase energy use by the body by acting on a part of the brain known as the hypothalamus.

To determine whether there might be an interplay between leptin and cannabinoids in the brain, Kunos and colleagues studied mice that had been specially bred to be missing a gene for a brain receptor for cannabinoid molecules. When the mice were given food after an 18-hour fast, they ate less food than did their littermates without the missing gene. In addition, when the mice were given a drug that blocks the action of the receptor, it suppressed the appetite of the normal mice but not of those with the missing receptor gene.

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