Endocannabinoid-Based Therapies
- 6 January 2022
- journal article
- review article
- Published by Annual Reviews in Annual Review of Pharmacology and Toxicology
- Vol. 62 (1), 483-507
- https://doi.org/10.1146/annurev-pharmtox-052220-021800
Abstract
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, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.Keywords
This publication has 160 references indexed in Scilit:
- The Serine Hydrolase ABHD6 Is a Critical Regulator of the Metabolic SyndromeCell Reports, 2013
- Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's DiseaseCell Reports, 2012
- Endocannabinoids Shape Accumbal Encoding of Cue-Motivated Behavior via CB1 Receptor Activation in the Ventral TegmentumNeuron, 2012
- Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in ratsPharmacological Research, 2011
- Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 Å resolutionProtein Science, 2011
- Crystal Structure of Fatty Acid Amide Hydrolase Bound to the Carbamate Inhibitor URB597: Discovery of a Deacylating Water Molecule and Insight into Enzyme InactivationJournal of Molecular Biology, 2010
- Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer PathogenesisCell, 2010
- Fatty Acid Amide Hydrolase Inhibition Heightens Anandamide Signaling Without Producing Reinforcing Effects in PrimatesBiological Psychiatry, 2008
- Full Mass Spectrometric Characterization of Human Monoacylglycerol Lipase Generated by Large-Scale Expression and Single-Step PurificationJournal of Proteome Research, 2008
- A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2-ArachidonoylglycerolCell Chemical Biology, 2007