Cannabidiol, extracted fromCannabis sativa, selectively inhibits inflammatory hypermotility in mice

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Abstract
Background and purpose: Cannabidiol is aCannabis‐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: Motilityin vivowas measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; contractilityin vitrowas 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 CB1receptor antagonist rimonabant, but not by the cannabinoid CB2receptor 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) inhibitorN‐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 micein vivoand this effect involves cannabinoid CB1receptors 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

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