期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
卷 61, 期 -, 页码 441-463出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-030220-112741
关键词
THC; endocannabinoids; FAAH; MAGL; cannabinoid receptor
资金
- VICI grant from the Netherlands Organization for Scientific Research
- Oncode Institute
Researchers have developed compounds to modulate the endocannabinoid system in the human brain, including inhibitors of FAAH and MAGL to exert therapeutic effects without inducing adverse reactions associated with direct stimulation of the CB1 receptor by THC. These compounds have potential for treatment without the side effects of THC.
Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (-)-trans-Delta(9)-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB1 receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.
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