George Kunos MD., PhD. Chief LPS

George Kunos M.D., Ph.D. Chief
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
5625 Fishers Lane, Room 2S-24:MSC 9413
Bethesda MD 20892-9413
telephone: +1 301.443.2069
fax: +1 301.480.0257



The Section on Neuroendocrinology focuses on the endocannabinoid system, which is involved in the regulation of appetite and the metabolism of lipids, and is therefore implicated in obesity, alcoholism and cardiovascular disease. The Section previously provided the first evidence that mice deficient in the cannabinoid receptor CB1 showed reduced food intake following temporary food deprivation. However, the use of rimonabant (a CB1 antagonist) for obesity was abandoned due to neuropsychiatric side effects, so the Section is currently testing other CB1 antagonists with limited brain penetration. The Section is particularly interested in AM6545. It has used mouse models of obesity to show that AM6545 does not affect behavioral responses mediated by CB1 receptors in the brain, and that the compound significantly reduced weight without reducing caloric intake. The Section is currently conducting similar experiments on JD-5037, another CB1 antagonist with limited brain penetrance. The Section is also studying fatty-acid hydrolase (FAAH), an enzyme that catalyzes the degradation of the endocannabinoid anandamide. In vivo experiments with hypertensive rats have shown that AM3506 (an FAAH inhibitor) normalizes elevated blood pressure and cardiac contractility without causing hyperglycemia or insulin resistance.