First, CBD acts as a noncompetitive negative allosteric modulator of CB1R, exerting weak agonist effects on this receptor, and therefore, it does not cause either the psychotropic effects of THC [116,117], or the depressive effects observed with rimonabant, which is an inverse antagonist of CB1R that was initially approved by the European Union for the treatment of obesity and its comorbidities, such as NAFLD and NASH [118]. Here, CNR1 is linked to obesity due to melanocortin 4 receptor deficiency.