Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis

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-1β 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-1β, 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.

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Abbreviations

2-AG:

2-Arachydonylglycerol

CBD:

Cannabidiol

COX-2:

Cyclooxygenase-2

DMEM:

Dulbecco's modified Eagle’s medium

DNBS:

2,4,6-Dinitrobenzene sulfonic acid

ELISA:

Enzyme-linked immunosorbent assay

FAAH:

Fatty acid amide hydrolase

FBS:

Fetal bovine serum

iNOS:

Inducible nitric oxide synthase

H2DCF-DA:

2′,7′-Dichlorfluorescein-diacetate

IL-1β:

Interleukin-1β

IL-10:

Interleukin 10

MDA:

Malondialdehyde

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PBS:

Phosphate-buffered saline

ROS:

Reactive oxygen species

TBA:

Thiobarbituric acid

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Acknowledgments

We are grateful to GW Pharmaceuticals (Porton Down, Wiltshire, UK) for providing us cannabidiol.

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Correspondence to Angelo A. Izzo.

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Francesca Borrelli, Gabriella Aviello, Barbara Romano, Pierangelo Orlando, Rafaelle Capasso, Federico Guadagno, Stefania Petrosino, Vincenzo Di Marzo, and Angelo A, Izzo are members of the Endocannabinoid Research Group.

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Borrelli, F., Aviello, G., Romano, B. et al. Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis. J Mol Med 87, 1111 (2009). https://doi.org/10.1007/s00109-009-0512-x

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Keywords

  • Cannabinoids
  • Colitis
  • Inflammatory bowel disease
  • Gastroenterology