Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice

R Capasso, F Borrelli, G Aviello, B Romano, C Scalisi, F Capasso, A A Izzo

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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 alpha2-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.

Original languageEnglish
Pages (from-to)1001-1008
Number of pages8
JournalBritish Journal of Pharmacology
Volume154
Issue number5
DOIs
Publication statusPublished - Jul 2008

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Cannabidiol
Cannabis
Croton Oil
Cannabinoid Receptor Antagonists
rimonabant
Ileum
Adrenergic alpha-2 Receptor Antagonists
Loperamide
Inflammation
Cannabinoid Receptor CB1
Gastrointestinal Motility
Yohimbine
Narcotic Antagonists
Irritants
Neuroprotective Agents
Naloxone
Baths
Inflammatory Bowel Diseases
Small Intestine
Gastrointestinal Tract

Keywords

  • Acetylcholine
  • Amidohydrolases
  • Animals
  • Cannabidiol
  • Cannabis
  • Cholinergic Agents
  • Croton Oil
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • Gastrointestinal Agents
  • Gastrointestinal Motility
  • Gastrointestinal Transit
  • Ileitis
  • Ileum
  • Loperamide
  • Male
  • Mice
  • Mice, Inbred ICR
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Capasso, R., Borrelli, F., Aviello, G., Romano, B., Scalisi, C., Capasso, F., & Izzo, A. A. (2008). Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. British Journal of Pharmacology, 154(5), 1001-1008. https://doi.org/10.1038/bjp.2008.177

Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. / Capasso, R; Borrelli, F; Aviello, G; Romano, B; Scalisi, C; Capasso, F; Izzo, A A.

In: British Journal of Pharmacology, Vol. 154, No. 5, 07.2008, p. 1001-1008.

Research output: Contribution to journalArticle

Capasso, R, Borrelli, F, Aviello, G, Romano, B, Scalisi, C, Capasso, F & Izzo, AA 2008, 'Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice', British Journal of Pharmacology, vol. 154, no. 5, pp. 1001-1008. https://doi.org/10.1038/bjp.2008.177
Capasso, R ; Borrelli, F ; Aviello, G ; Romano, B ; Scalisi, C ; Capasso, F ; Izzo, A A. / Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. In: British Journal of Pharmacology. 2008 ; Vol. 154, No. 5. pp. 1001-1008.
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N2 - 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 alpha2-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.

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KW - Enzyme Inhibitors

KW - Gastrointestinal Agents

KW - Gastrointestinal Motility

KW - Gastrointestinal Transit

KW - Ileitis

KW - Ileum

KW - Loperamide

KW - Male

KW - Mice

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KW - Piperidines

KW - Pyrazoles

KW - Receptor, Cannabinoid, CB1

KW - Journal Article

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