CNR1 and obesity due to melanocortin 4 receptor deficiency: The endocannabinoid system in the brain facilitates food intake, and its overactivity is implicated in the etiology of obesity.42,43 Key neural circuitry underlying these effects includes the hypothalamus and the limbic forebrain, where endocannabinoid levels rise during periods of hunger.44 In order to interfere with such endocannabinoid hunger signals, the CB1R inverse agonist rimonabant was marketed to treat obesity in humans.