Targeting the endocannabinoid system in diabesity: Fact or fiction?

'Diabesity' refers to a rising epidemic indicated by the intricate relationship between obesity and diabetes. The global prevalence of these coexisting, insidious diseases increases social and economic health burdens at a rapid pace. Numerous reports delineate the involvement of the underlying endocannabinoid (EC) signaling system through the cannabinoid-1 (CB1) receptor in the regulation of metabolism and adiposity. Conversely, EC inverse agonists can result in severe depression and suicidal thoughts through interactions with CB1/2 receptors in the brain. This review attempts to elucidate a possible mechanism for the amelioration of diabesity. Moreover, we also highlight the available targets of the CB1 receptor, which could pave the way for safe and effective therapy.