Endocannabinoid-Based Therapies.

Annual Review of Pharmacology and Toxicology
Daniele Piomelli, Alex Mabou Tagne


The endocannabinoids are lipid-derived messengers that play a diversity of regulatory roles in mammalian physiology. Dysfunctions in their activity have been implicated in various disease conditions, attracting attention to the endocannabinoid system as a possible source of therapeutic drugs. This signaling complex has three components: the endogenous ligands, anandamide and 2-arachidonoyl-sn-glycerol (2-AG); a set of enzymes and transporters that generate, eliminate, or modify such ligands; and selective cell surface receptors that mediate their biological actions. We provide an overview of endocannabinoid formation, deactivation, and biotransformation and outline the properties and therapeutic potential of pharmacological agents that interfere with those processes. We describe small-molecule inhibitors that target endocannabinoid-producing enzymes, carrier proteins that transport the endocannabinoids into cells, and intracellular endocannabinoid-metabolizing enzymes. We briefly discuss selected agents that simultaneously interfere with components of the endocannabinoid system and with other functionally related signaling pathways. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Vol...Continue Reading

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