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.
KeywordsCannabinoid receptors Intestinal motility Intestinal secretion Emesis Intestinal inflammation Feeding
Unable to display preview. Download preview PDF.
- Akiba Y, Nakamura M, Ishii H (2001) Immunolocalization of vanilloid receptor-1 (VR-1) in CGRP-positive neurons and interstitial cells of Cajal in the myenteric plexus of the rat gastrointestinal tract. Gastroenterology 120:1721Google Scholar
- Coutts AA (2004) Cannabinoid receptor activation and the endocannabinoid system in the gastrointestinal tract. Curr Neuropharmacol 2:91–102Google Scholar
- Guanini F, Croci T, Aureggi G, Manara L, Rinaldi-Carmona M, Mukenge S, Aldrighetti L, Ferla G, Maffrand J-P, Le Fur G (2000) Tolerance to (+)WIN55,212-2 inhibitory effect and withdrawal by the cannabinoid CB1 receptor antagonist SR 141716 in isolated strips of small intestine. International Cannabinoid Research Society symposium on the Cannabinoids, Burlington, VermontGoogle Scholar
- Heshmati H, Caplain H, Bellisle F, Mosse M, Fauveau C, Le Fur G (2001) SR141716, a selective CB1 receptor cannabinoid receptor antagonist reduces hunger, caloric intake, and body weight in overweight or obese men. Obes Res 9:70SGoogle Scholar
- Izzo AA, Capasso F, Costagliola A, Bisogno T, Marsicano G, Ligresti A, Matias I, Capasso R, Pinto L, Borrelli F, Cecio A, Lutz B, Mascolo N, Di Marzo V (2003) An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice. Gastroenterology 125:765–774PubMedCrossRefGoogle Scholar
- MacNaughton WK, Cushing K, Van Sickle MD, Keenan CM, Mackie K, Sharkey KA (2003) Cannabinoid CB1 receptor distribution and function in neurally mediated chloride secretion in the guinea pig ileum. Gastroenterology 124:A342Google Scholar
- MacNaughton WK, Van Sickle MD, Keenan CM, Cushing K, Mackie K, Sharkey KA (2004) Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves. Am J Physiol Gastrointest Liver Physiol (in press)Google Scholar
- Morrone LA, Romanelli L, Mazzanti G, Valeri P, Menichin F (1993) Hashish antagonism on the in vitro development of withdrawal contracture. Pharmacol Res 27(Suppl 1):63–64Google Scholar
- Parker LA, Mechoulam R (2003) Cannabinoid agonists and antagonists modulate lithium-induced conditioned gaping in rats. Integr Physiol Behav Sci 38:134–146Google Scholar
- Pertwee RG, Fernando S, Ritchie JEA (1998) Preliminary validation of a novel experimental model for the study of cannabinoid tolerance. International Cannabinoid Research Society symposium on the Cannabinoids, Burlington, VermontGoogle Scholar
- Rosell S, Agurell S, Martin BR (1976) Effects of cannabinoids on isolated smooth muscle preparations. New York, Springer-VerlagGoogle Scholar
- Tramer MR, Carroll D, Campbell FA, Reynolds DJM, Moore RA, McQuay HJ (2001) Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. Br Med J 323:16–21Google Scholar