ABSTRACT
Preparations of Cannabis sativa have been known for centuries to stimulate appetite, inhibit emesis, and improve a variety of other gastrointestinal disorders including gastrointestinal pain, flatulence, gastroenteritis, Crohn’s disease, diarrhoea, anddiabetic gastroparesis (1-5). Themain psychotropic constituent of Cannabis sativa is 9-tetrahydrocannabinol, which activates CB1 receptors (present in central and peripheral nerves, including the enteric nervous system) and CB2 receptors (expressedmainly in immune cells) (6,7). A general feature of CB1 activation is the reduction in the release of a variety of neurotransmitters, including acetylcholine from enteric nerves. Endogenous ligands for the cannabinoid receptors have been identified; the best knowns are anandamide and 2-arachidonylglycerol (2-AG) (8). Endocannabinoids are biosynthesized “on demand” and released from cells immediately after their production. Endocannabinoid levels in the gut appear to be elevated as an adaptive reaction to re-establish normal homeostasis when this is acutely and pathologically perturbed. For example, noxious stimuli (9-12), food deprivation (13), or clinically diagnosed gut diseases [e.g., inflammatory bowel disease (IBD), colorectal cancer, diverticulitis, and celiac disease] (14-17) produced measurable increases in intestinal endocannabinoid (mainly anandamide) levels.
