The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders

The skin is the largest organ of the body and has a complex and very active structure that contributes to homeostasis and provides the first line defense against injury and infection. In the past few years it has become evident that the endocannabinoid system (ECS) plays a relevant role in healthy and diseased skin. Specifically, we review how the dysregulation of ECS has been associated to dermatological disorders such as atopic dermatitis, psoriasis, scleroderma and skin cancer. Therefore, the druggability of the ECS could open new research avenues for the treatment of the pathologies mentioned. Numerous studies have reported that phytocannabinoids and their biological analogues modulate a complex network pharmacology involved in the modulation of ECS, focusing on classical cannabinoid receptors, transient receptor potential channels (TRPs), and peroxisome proliferator-activated receptors (PPARs). The combined targeting of several end-points seems critical to provide better chances of therapeutically success, in sharp contrast to the one-disease-one-target dogma that permeates current drug discovery campaigns.