Should peripheral CB1 cannabinoid receptors be selectively targeted for therapeutic gain?

Endocannabinoids, endogenous lipid ligands of cannabinoid receptors, mediate a variety of effects similar to those of marijuana. Cannabinoid CB1 receptors are highly abundant in the brain and mediate psychotropic effects, which limits their value as a potential therapeutic target. There is growing evidence for CB1 receptors in peripheral tissues that modulate a variety of functions, including pain sensitivity and obesity-related hormonal and metabolic abnormalities. In this review we propose that selective targeting of peripheral CB1 receptors has potential therapeutic value because it would help to minimize addictive, psychoactive effects in the case of CB1 agonists used as analgesics, or depression and anxiety in the case of CB1 antagonists used in the management of cardiometabolic risk factors associated with the metabolic syndrome.