Cannabidiol, a Safe and Non-Psychotropic Ingredient of the Marijuana Plant Cannabis Sativa, Is Protective in a Murine Model of Colitis

J Mol Med (Berl). 2009 Nov;87(11):1111-21. doi: 10.1007/s00109-009-0512-x. Epub 2009 Aug 20.

Abstract

Inflammatory bowel disease affects millions of individuals; nevertheless, pharmacological treatment is disappointingly unsatisfactory. Cannabidiol, a safe and non-psychotropic ingredient of marijuana, exerts pharmacological effects (e.g., antioxidant) and mechanisms (e.g., inhibition of endocannabinoids enzymatic degradation) potentially beneficial for the inflamed gut. Thus, we investigated the effect of cannabidiol in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzene sulfonic acid. Inflammation was assessed both macroscopically and histologically. In the inflamed colon, cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) were evaluated by Western blot, interleukin-1beta and interleukin-10 by ELISA, and endocannabinoids by isotope dilution liquid chromatography-mass spectrometry. Human colon adenocarcinoma (Caco-2) cells were used to evaluate the effect of cannabidiol on oxidative stress. Cannabidiol reduced colon injury, inducible iNOS (but not cyclooxygenase-2) expression, and interleukin-1beta, interleukin-10, and endocannabinoid changes associated with 2,4,6-dinitrobenzene sulfonic acid administration. In Caco-2 cells, cannabidiol reduced reactive oxygen species production and lipid peroxidation. In conclusion, cannabidiol, a likely safe compound, prevents experimental colitis in mice.

MeSH terms

  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Caco-2 Cells
  • Cannabidiol / pharmacology
  • Cannabidiol / therapeutic use*
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabis / chemistry*
  • Cell Survival / drug effects
  • Colitis / prevention & control*
  • Colon / drug effects
  • Colon / pathology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Gene Expression / drug effects
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Organ Size / drug effects

Substances

  • Antioxidants
  • Cannabinoid Receptor Modulators
  • Interleukin-1beta
  • Interleukin-10
  • Cannabidiol
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Amidohydrolases
  • fatty-acid amide hydrolase