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

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; I2 = 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; I2 not assessed). Cannabinoids reduced MPO in rodents compared to the vehicle; SMD -1.26; 95% CI, -1.54 to -0.97; I2 = 48.1%. Cannabigerol had the largest effect size (SMD -6.20; 95% CI, -9.90 to -2.50), followed by the synthetic CB1 agonist ACEA (SMD -3.15; 95% CI, -4.75 to -1.55) and synthetic CB1/2 agonist WIN55,212-2 (SMD -1.74; 95% CI, -2.81 to -0.67; I2 = 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.