Cannabinoids and the digestive tract.
In the digestive tract there is evidence for the presence of high levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and enzymes involved in the synthesis and metabolism of endocannabinoids. Immunohistochemical studies have shown the presence of CB1 receptors on myenteric and submucosal nerve plexuses along the alimentary tract. Pharmacological studies have shown that activation of CB1 receptors produces relaxation of the lower oesophageal sphincter, inhibition of gastric motility and acid secretion, as well as intestinal motility and secretion. In general, CB1-induced inhibition of intestinal motility and secretion is due to reduced acetylcholine release from enteric nerves. Conversely, endocannabinoids stimulate intestinal primary sensory neurons via the vanilloid VR1 receptor, resulting in enteritis and enhanced motility. The endogenous cannabinoid system has been found to be involved in the physiological control of colonic motility and in some pathophysiological states, including paralytic ileus, intestinal inflammation and cholera toxin-induced diarrhoea. Cannabinoids also possess antiemetic effects mediated by activation of central and peripheral CB1 receptors. Pharmacological modulation of the endogenous cannabinoid system could provide a new therapeutic target for the treatment of a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, secretory diarrhoea, paralytic ileus, inflammatory bowel disease, colon cancer and gastro-oesophageal reflux conditions.
Izzo
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Department of Experimental Pharmacology, University of Naples Federico II, via D Montesano 49, 80131 Naples, Italy.
Coutts
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AA
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D004361:Drug Tolerance; D049630:Esophageal Sphincter, Lower / Q000187:drug effects / Q000502:physiology; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D002189:Marijuana Abuse; D013276:Stomach Ulcer / Q000188:drug therapy; D009435:Synaptic Transmission / Q000187:drug effects; D050916:TRPV Cation Channels / Q000819:agonists; D014839:Vomiting / Q000188:drug therapy
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D050916:TRPV Cation Channels; C494484:TRPV1 receptor