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Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice
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Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice
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Journal Article
Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice
2008
Overview
Background and purpose: Cannabidiol is a Cannabis‐derived non‐psychotropic compound that exerts a plethora of pharmacological actions, including anti‐inflammatory, neuroprotective and antitumour effects, with potential therapeutic interest. However, the actions of cannabidiol in the digestive tract are largely unexplored. In the present study, we investigated the effect of cannabidiol on intestinal motility in normal (control) mice and in mice with intestinal inflammation. Experimental approach: Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with ACh. Key results: In vivo, cannabidiol did not affect motility in control mice, but normalized croton oil‐induced hypermotility. The inhibitory effect of cannabidiol was counteracted by the cannabinoid CB1 receptor antagonist rimonabant, but not by the cannabinoid CB2 receptor antagonist SR144528 (N‐[‐1S‐endo‐1,3,3‐trimethyl bicyclo [2.2.1] heptan‐2‐yl]‐5‐(4‐chloro‐3‐methylphenyl)‐1‐(4‐methylbenzyl)‐pyrazole‐3‐carboxamide), by the opioid receptor antagonist naloxone or by the α2‐adrenergic antagonist yohimbine. Cannabidiol did not reduce motility in animals treated with the fatty acid amide hydrolase (FAAH) inhibitor N‐arachidonoyl‐5‐hydroxytryptamine, whereas loperamide was still effective. In vitro, cannabidiol inhibited ACh‐induced contractions in the isolated ileum from both control and croton oil‐treated mice. Conclusions and implications: Cannabidiol selectively reduces croton oil‐induced hypermotility in mice in vivo and this effect involves cannabinoid CB1 receptors and FAAH. In view of its low toxicity in humans, cannabidiol may represent a good candidate to normalize motility in patients with inflammatory bowel disease. British Journal of Pharmacology (2008) 154, 1001–1008; doi:10.1038/bjp.2008.177; published online 12 May 2008
Publisher
Blackwell Publishing Ltd,Nature Publishing,Nature Publishing Group
Subject
/ Amidohydrolases - antagonists & inhibitors
/ Amidohydrolases - metabolism
/ Animals
/ Biological and medical sciences
/ Cholinergic Agents - pharmacology
/ Croton
/ Dose-Response Relationship, Drug
/ Enzyme Inhibitors - pharmacology
/ Gastroenterology. Liver. Pancreas. Abdomen
/ Gastrointestinal Agents - pharmacology
/ Gastrointestinal Motility - drug effects
/ Gastrointestinal Transit - drug effects
/ Ileitis - chemically induced
/ Male
/ Mice
/ Pharmacology. Drug treatments
