The discovery of the endocannabinoid system (ECS; comprising of G-protein coupled cannabinoid 1 and 2 receptors, their endogenous lipid ligands or endocannabinoids, and synthetic and metabolizing enzymes, triggered an avalanche of experimental studies that have implicated the ECS in a growing number of physiological/pathological functions. They also suggested that modulating ECS activity holds therapeutic promise for a broad range of diseases, including neurodegenerative, cardiovascular and inflammatory disorders, obesity/metabolic syndrome, cachexia, chemotherapy-induced nausea and vomiting, tissue injury and pain, among others. However, clinical trials with globally acting CB1 antagonists in obesity/metabolic syndrome, and other studies with peripherally restricted CB1/2 agonists and inhibitors of the endocannabinoid...