Modification of cardiometabolic risk through cannabinoid type-1 receptor antagonism

Large-scale epidemiological studies show that hypertension, diabetes, and dyslipidaemia are highly prevalent among obese individuals. Regrettably, preventive efforts have failed to abolish the increasing prevalence of obesity worldwide. The endocannabinoid system is implicated in the regulation of appetite, food intake, lipids, and glucose metabolism. Rimonabant is the first type-1 endocannabinoid receptor blocker that has been shown to improve the serum lipid profile, insulin and glucose levels, and blood pressure. In particular, the RIO (rimonabant in obesity) studies documented the beneficial metabolic effects of rimonabant. These favorable metabolic effects exceed by about 50% those anticipated by weight reduction, possibly due to modulation of the endocannabinoid system in peripheral tissues. The beneficial effects, however, seem to come at the cost of an increased risk of psychiatric disorders. However, given the efficacy of this treatment and the magnitude of the obesity problem, rimonabant may prove to be a valuable adjunct in targeting obesity-related cardiovascular risk factors.