Marijuana Munchies Hold Weight-Loss Clues

Biting into the science behind the "marijuana munchies," American researchers have uncovered clues to pot's effect on appetite. Their insights might also lead to drugs that could help increase -- or curb -- wayward appetites. The team of researchers at Columbia University, in New York City, didn't focus on the drug itself, but rather on the body's own version of pot's principal ingredient, tetrahydrocannabinol (THC). Naturally produced cannabinoid molecules, called endocannabinoids, are drawn to the hypothalamus -- a region of the brain that regulates hunger and other basic functions such as memory, perception and movement. Researchers have long known that once endocannabinoids dock with their brain receptors -- known as CB1s -- hunger ensues. What has not been understood is why. The new study conducted in mice reveals that specific CB1 neurons linked with hunger arousal are "excited" when cannabis molecules, such as THC or endocannabinoids, dock with CB1 receptors. This neural stimulation, in turn, ignites the need to feed. The authors also discovered that this endocannabinoid-induced hunger effect is tamped down by leptin -- a naturally produced hormone previously associated with the long-term regulation of body weight. In sufficient amounts leptin short-circuits the cannabis docking process -- maintaining a check on hunger by inhibiting the flow of calcium into the neurons, the researchers found. Leptin deficiency, on the other hand, seems to allow CB1 neuronal stimulation to continue unfettered for longer periods of time -- time presumably spent raiding the fridge. "In mice we see that without the leptin signal they become obese, because they have more endocannabinoids in the brain," said study author Young-Hwan Jo, formerly of Columbia University's Center for Neurobiology and Behavior, and currently with the department of medicine's endocrinology division at the Albert Einstein College of Medicine in New York City. Jo's team believe the findings could lead to appetite-stimulating drugs that could help ill patients such as those battling cancer or AIDS. New insights into the mechanics of hunger may also point to novel targets for weight-loss drugs that could manipulate the body's natural circuitry to control cravings. In fact, drugs that work on CB1 receptor blockers are already here -- most notably rimonabant (Acomplia), which is currently undergoing U.S. Food and Drug Administration review as a weight-loss aid. Although early clinical trials with rimonabant have proved promising, Jo noted that not even the drug's developers clearly understood the mechanism behind the new treatment. Until now. "Nobody has known how it works," said Jo. "So now maybe our study will provide at least the mechanism by which this new drug affects the brain and hunger." The Columbia team emphasized that their work to date has been limited to mice that were genetically altered to be leptin-deficient. Making the leap to designing effective human interventions could prove difficult at best, noted Richard Mattes, a professor of foods and nutrition at Purdue University. "Obtaining adequate energy is so vital to the survival of our species, that even if you can trick part of the hunger system for some period of time -- and what they've found may be part of the system -- other systems may come into play to work around that," said Mattes. "That's why sustained weight loss is so difficult," he added. "So while this is fundamental research and may provide a sound basis for the development of interventions in the future, we should all be cautious to jumping to the belief that there is a magic bullet. It's still a long way away from understanding eating behavior."