The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity

Crohn's disease and ulcerative colitis are two major forms of inflammatory bowel diseases (IBD), which are chronic inflammatory disorders of the gastrointestinal tract. These pathologies are currently under investigation to both unravel their etiology and find novel treatments. Anandamide and 2-arachidonoylglycerol are endogenous bioactive lipids that bind to and activate the cannabinoid receptors, and together with the enzymes responsible for their biosynthesis and degradation [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)] constitute the endocannabinoid system (ECS). The ECS is implicated in gut homeostasis, modulating gastrointestinal motility, visceral sensation, and inflammation, as well as being recently implicated in IBD pathogenesis. Numerous subsequent studies investigating the effects of cannabinoid agonists and endocannabinoid degradation inhibitors in rodent models of IBD have identified a potential therapeutic role for the ECS.