One of the widely reported effects of Cannabis or cannabinoids is their ability to stimulate appetite. This effect has been studied therapeutically, particularly in relation to cachexia and malnutrition associated with cancer, acquired immunodeficiency syndrome, and anorexia nervosa. Our understanding of the mechanism by which marijuana exerts its pharmacological actions increased considerably following the identification in the early 1990s of the sites of action of (DELTA)~9-tetrahydrocannabinol ((DELTA)~9-THC), the cannabinoid CB1 and CB2 receptors and, subsequently, of the endocannabinoids (i.e., the endogenous agonists anandamide and 2-arachydonylglicerol).A number of reports have suggested that the endogenous cannabinoid system may regulate energy balance and food intake at several functional levels, both in the brain and in the periphery. Sites of action of cannabinoids include the limbic system (for hedonic evaluation of foods), hypothalamus and hindbrain (integrative functions), intestinal tract, adipose tissue, skeletal muscle and liver. In a number of animal species, including in humans, the administration of exogenous and endogenous cannabinoids leads to robust increases in food intake and can promote body weight gain. These effects are believed to be mediated through activation of the CB1 receptors. Conversely, selective CB1 receptor antagonists may reduce food intake and body weight, with the effect being greater in obese animals. Such findings have led a number of pharmaceutical companies to develop selective CB1 receptor antagonists for the treatment of obesity. The most advanced of these antagonists is rimonabant. Clinical studies have recently demonstrated that rimonabant, combined with a hypocaloric diet over 1 year, promoted a significant decrease in body weight and waist circumference and an improvement in cardiovascular risk factors.
展开▼
