The Endogenous Cannabinoid System in the Gastrointestinal Tract

The digestive tract contains endogenous cannabinoids (anandamide and 2-arachidonylglycerol), enzymes involved in their synthesis and metabolism and cannabinoid receptors. CB1 receptors are mainly expressed on myenteric and submucosal nerve plexuses and their activation results in inhibition of neurotransmitters (mainly acetylcholine) release. CB2 receptors are mainly expressed on cells of immune system, with a possible role in pathophysiological states (e.g. inflammation). Action of cannabinoids in the digestive tract include inhibition of intestinal motility, gastric and intestinal secretion, inflammation, visceral pain and cell proliferation. Experimental evidence also suggests that anandamide (an orexic fatty acid ethanolamide) in the gut may act as a “hunger signal”, an action which could be counterbalanced by intestinal oleoylethanolamide (an anorexic fatty acid ethanolamide).