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.
The researchers also looked at other animals -- mice engineered for obesity, and mice and rats engineered for diabetes -- to determine whether leptin might have an effect on cannabinoids in the brain. They found that when normal and obese rodents were given leptin, brain levels of two naturally occurring cannabinoids were reduced. But when mice and rats with defects in the leptin system were given leptin, the cannabinoids were only slightly reduced, suggesting that leptin plays an important role in the release of chemicals that either suppress or enhance appetite.
The experiments indicate that specific cannabinoids in the brain may activate cannabinoid receptors to stimulate appetite and therefore maintain weight. They also suggest that naturally occurring cannabinoids form part of the appetite-control circuit in the brain, with leptin serving as a kind of master dimmer switch.
Kunos tells WebMD that while it is tempting to speculate about potential weight-loss drugs based on a cannabinoid receptor-blocking strategy, "there are so many of these [appetite controlling] hormones, one would think it logical that it would be very difficult to have a major effect on food intake by using only one or the other. A case in point was the clinical trials with leptin which were kind of disappointing in that leptin wasn't very effective in reducing food intake, even though it's a very powerful orchestrating hormone, probably because other components of the system kicked in and compensated."