Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice

Angelo A Izzo, Raffaele Capasso, Gabriella Aviello, Francesca Borrelli, Barbara Romano, Fabiana Piscitelli, Laura Gallo, Francesco Capasso, Pierangelo Orlando, Vincenzo Di Marzo

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Abstract

BACKGROUND AND PURPOSE: Cannabichromene (CBC) is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). Both endocannabinoids and TRPA1 may modulate gastrointestinal motility. Here, we investigated the effect of CBC on mouse intestinal motility in physiological and pathological states.

EXPERIMENTAL APPROACH: Inflammation was induced in the mouse small intestine by croton oil. Endocannabinoid (anandamide and 2-arachidonoyl glycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry; TRPA1 and cannabinoid receptors were analysed by quantitative RT-PCR; upper gastrointestinal transit, colonic propulsion and whole gut transit were evaluated in vivo; contractility was evaluated in vitro by stimulating the isolated ileum, in an organ bath, with ACh or electrical field stimulation (EFS).

KEY RESULTS: Croton oil administration was associated with decreased levels of anandamide (but not 2-arachidonoyl glycerol) and palmitoylethanolamide, up-regulation of TRPA1 and CB₁ receptors and down-regulation of CB₂ receptors. Ex vivo CBC did not change endocannabinoid levels, but it altered the mRNA expression of TRPA1 and cannabinoid receptors. In vivo, CBC did not affect motility in control mice, but normalized croton oil-induced hypermotility. In vitro, CBC reduced preferentially EFS- versus ACh-induced contractions. Both in vitro and in vivo, the inhibitory effect of CBC was not modified by cannabinoid or TRPA1 receptor antagonists.

CONCLUSION AND IMPLICATIONS: CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1.

Original languageEnglish
Pages (from-to)1444-1460
Number of pages17
JournalBritish Journal of Pharmacology
Volume166
Issue number4
Early online date17 May 2012
DOIs
Publication statusPublished - Jun 2012

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Keywords

  • Animals
  • Arachidonic Acids
  • Cannabinoids
  • Cannabis
  • Duodenum
  • Endocannabinoids
  • Ethanolamines
  • Gastrointestinal Agents
  • Gastrointestinal Motility
  • Gene Expression Regulation
  • Ileitis
  • Ileum
  • In Vitro Techniques
  • Jejunum
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscle Contraction
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Transient Receptor Potential Channels
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Izzo, A. A., Capasso, R., Aviello, G., Borrelli, F., Romano, B., Piscitelli, F., Gallo, L., Capasso, F., Orlando, P., & Di Marzo, V. (2012). Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. British Journal of Pharmacology, 166(4), 1444-1460. https://doi.org/10.1111/j.1476-5381.2012.01879.x