The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis

Abstract

Background Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammation. We collated studies examining outcomes for meta-analysis from EMBASE, MEDLINE and Pubmed until March 2017. Quality was assessed according to mSTAIR and SRYCLE score. Results From 2008 papers, 51 publications examining the effect of cannabinoid compounds on murine colitis and 2 clinical studies were identified. Twenty-four compounds were assessed across 71 endpoints. Cannabidiol, a phytocannabinoid, was the most investigated drug. Macroscopic colitis severity (disease activity index [DAI]) and myeloperoxidase activity (MPO) were assessed throughout publications and were meta-analyzed using random effects models. Cannabinoids reduced DAI in comparison with the vehicle (standard mean difference [SMD] -1.36; 95% CI, -1.62 to-1.09; I 2 = 61%). FAAH inhibitor URB597 had the largest effect size (SMD -4.43; 95% CI, -6.32 to -2.55), followed by the synthetic drug AM1241 (SMD -3.11; 95% CI, -5.01 to -1.22) and the endocannabinoid anandamide (SMD -3.03; 95% CI, -4.89 to -1.17; I 2 not assessed). Cannabinoids reduced MPO in rodents compared to the vehicle; SMD -1.26; 95% CI, -1.54 to -0.97; I 2 = 48.1%. Cannabigerol had the largest effect size (SMD -6.20; 95% CI, -9.90 to -2.50), followed by the synthetic CB 1 agonist ACEA (SMD -3.15; 95% CI, -4.75 to -1.55) and synthetic CB 1/2 agonist WIN55,212-2 (SMD -1.74; 95% CI, -2.81 to -0.67; I 2 = 57%). We found no evidence of reporting bias. No significant difference was found between the prophylactic and therapeutic use of cannabinoid drugs. Conclusions There is abundant preclinical literature demonstrating the anti-inflammatory effects of cannabinoid drugs in inflammation of the gut. Larger randomised controlled-trials are warranted.