Pharmacotherapeutic modulation of the endocannabinoid signalling system in psychiatric disorders: drug-discovery strategies.
Medicinal chemistry has produced small-molecule agents with drug-like character that potently and safely modulate the activity of discrete endocannabinoid system components as potential treatments for medical disorders, including various psychiatric conditions. Two cannabinoid (CB) receptors (CB1 and CB2) currently represent prime endocannabinoid-system therapeutic targets for ligands that either mimic endocannabinoid signalling processes and/or potentiate endocannabinoid-system activity (agonists) or attenuate pathologically heightened endocannabinoid-system transmission (antagonists). Two endocannabinoid deactivating enzymes, fatty acid amide hydrolase (FAAH) and soluble monoacylglycerol lipase (MGL), are increasingly prominent targets for inhibitors that indirectly potentiate endocannabinoid-system signalling. Continued profiling of drug candidates in relevant disease models, identification of additional cannabinoid-related therapeutic targets, and validation of new pharmacological modes of endocannabinoid system modulation will undoubtedly invite further translational efforts in the cannabinoid field for treating psychiatric disorders and other medical conditions.
Center for Drug Discovery, Northeastern University, Boston, Massachusetts 02115-5000, USA.
David R
DR
Janero
Subramanian K
SK
Vadivel
Alexandros
A
Makriyannis
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis* / Q000494:pharmacology*; D002186:Cannabinoids / Q000138:chemical synthesis / Q000494:pharmacology; D055808:Drug Discovery; D063388:Endocannabinoids; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000503:physiopathology; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D008994:Monoacylglycerol Lipases; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases