An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

Ester Pagano,Fabiana Piscitelli,Angelo A Izzo,Francesca Borrelli,Anna Lauritano,Raffaele Capasso,Olga A Parisi,Stefania Finizio,Barbara Romano,Vincenzo Di Marzo

doi:10.3389/fphar.2016.00341

Ester Pagano, Fabiana Piscitelli + Show 8 more

Open Access

https://doi.org/10.3389/fphar.2016.00341

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Abstract

Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage – after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

Highlights

Inflammatory bowel disease (IBD) is a a chronic immunologically mediated disease with growing incidence and prevalence rates in industrialized countries (Ananthakrishnan, 2015; Taleban et al, 2015)
We have examined the effect of CBD BDS in the murine model of colitis induced by dinitrobenzenesulfonic acid
The dose of CBD BDS used in the experiments refers to the amount of CBD contained in the extract (e.g., 10 mg/kg of CBD BDS indicates a dose of the BDS that contains 10 mg/kg of CBD). 2,4,6-dinitrobenzenesulfonic acid (DNBS), croton oil and myeloperoxidase (MPO) from human leucocytes, were purchased from Sigma Aldrich S.r.l. (Milan, Italy)

Summary

Introduction

Inflammatory bowel disease (IBD) is a a chronic immunologically mediated disease with growing incidence and prevalence rates in industrialized countries (Ananthakrishnan, 2015; Taleban et al, 2015). The anecdotal use of marijuana and/or preparations from Cannabis sativa L. (hemp) in IBD patients has been recently confirmed by Cannabis Extract and Intestinal Inflammation investigations in humans (Ravikoff Allegretti et al, 2013; Naftali et al, 2014; Storr et al, 2014; Izzo et al, 2015). The most known among the phytocannabinoids is 9-tetrahydrocannabinol (THC), whose possible clinical use is hindered by its psychoactivity. This obstacle has addressed further research toward non-psychotropic phytocannabinoids such as cannabidiol (CBD), the versatile pharmacology of which is well established (Esposito et al, 2013; Welty et al, 2014; Brodie et al, 2015; Burstein, 2015; McPartland et al, 2015)

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