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Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice.
Br J Pharmacol 2012; 166(4):1444-60BJ

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.

Authors+Show Affiliations

Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy. aaizzo@unina.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22300105

Citation

Izzo, Angelo A., et al. "Inhibitory Effect of Cannabichromene, a Major Non-psychotropic Cannabinoid Extracted From Cannabis Sativa, On Inflammation-induced Hypermotility in Mice." British Journal of Pharmacology, vol. 166, no. 4, 2012, pp. 1444-60.
Izzo AA, Capasso R, Aviello G, et al. Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. Br J Pharmacol. 2012;166(4):1444-60.
Izzo, A. A., Capasso, R., Aviello, G., Borrelli, F., Romano, B., Piscitelli, F., ... 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), pp. 1444-60. doi:10.1111/j.1476-5381.2012.01879.x.
Izzo AA, et al. Inhibitory Effect of Cannabichromene, a Major Non-psychotropic Cannabinoid Extracted From Cannabis Sativa, On Inflammation-induced Hypermotility in Mice. Br J Pharmacol. 2012;166(4):1444-60. PubMed PMID: 22300105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. AU - Izzo,Angelo A, AU - Capasso,Raffaele, AU - Aviello,Gabriella, AU - Borrelli,Francesca, AU - Romano,Barbara, AU - Piscitelli,Fabiana, AU - Gallo,Laura, AU - Capasso,Francesco, AU - Orlando,Pierangelo, AU - Di Marzo,Vincenzo, PY - 2012/2/4/entrez PY - 2012/2/4/pubmed PY - 2012/10/10/medline SP - 1444 EP - 60 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 166 IS - 4 N2 - 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/22300105/Inhibitory_effect_of_cannabichromene_a_major_non_psychotropic_cannabinoid_extracted_from_Cannabis_sativa_on_inflammation_induced_hypermotility_in_mice_ L2 - https://doi.org/10.1111/j.1476-5381.2012.01879.x DB - PRIME DP - Unbound Medicine ER -