Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors

Annu Rev Pharmacol Toxicol. 2021 Jan 6:61:441-463. doi: 10.1146/annurev-pharmtox-030220-112741. Epub 2020 Aug 31.

Abstract

Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (-)-trans9-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.

Keywords: FAAH; MAGL; THC; cannabinoid receptor; endocannabinoids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amidohydrolases
  • Endocannabinoids*
  • Enzyme Inhibitors*
  • Humans
  • Lipase

Substances

  • Endocannabinoids
  • Enzyme Inhibitors
  • Lipase
  • Amidohydrolases
  • fatty-acid amide hydrolase