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...

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Main Authors: Couch, Daniel G., Maudslay, Henry, Doleman, Brett, Lund, Jonathan N., O'Sullivan, Saoirse
Format: Article
Language:English
Published: Lippincott, Williams & Wilkins 2018
Subjects:
Online Access:https://eprints.nottingham.ac.uk/49221/
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author Couch, Daniel G.
Maudslay, Henry
Doleman, Brett
Lund, Jonathan N.
O'Sullivan, Saoirse
author_facet Couch, Daniel G.
Maudslay, Henry
Doleman, Brett
Lund, Jonathan N.
O'Sullivan, Saoirse
author_sort Couch, Daniel G.
building Nottingham Research Data Repository
collection Online Access
description 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 endocannabinoid system in intestinal inflammation. We collated studies examining outcomes for metaanalysis 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 two clinical studies were identified. 24 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-analysed using random effects models. Cannabinoids reduced DAI in comparison with vehicle; 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,-2.55), followed by the synthetic drug AM1241 (SMD–3.11, 95% CI -5.01, -1.22) and the endocannabinoid anandamide (SMD-3.03, 95% CI -4.89,-1.17, I² not assessed). Cannabinoids reduced MPO in rodents compared to 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, -2.50), followed by the synthetic CB₁ agonist ACEA(SMD -3.15, 95%CI-4.75, -1.55) and synthetic CB₁/₂ agonist WIN55,212-2(SMD-1.74, 95%CI-2.81, -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 pre-clinical literature demonstrating the anti-inflammatory effects of cannabinoid drugs in inflammation of the gut. Larger randomised controlled-trials are warranted.
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spelling nottingham-492212019-03-19T04:30:10Z https://eprints.nottingham.ac.uk/49221/ The use of cannabinoids in colitis: a systematic review and meta-analysis Couch, Daniel G. Maudslay, Henry Doleman, Brett Lund, Jonathan N. O'Sullivan, Saoirse 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 endocannabinoid system in intestinal inflammation. We collated studies examining outcomes for metaanalysis 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 two clinical studies were identified. 24 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-analysed using random effects models. Cannabinoids reduced DAI in comparison with vehicle; 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,-2.55), followed by the synthetic drug AM1241 (SMD–3.11, 95% CI -5.01, -1.22) and the endocannabinoid anandamide (SMD-3.03, 95% CI -4.89,-1.17, I² not assessed). Cannabinoids reduced MPO in rodents compared to 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, -2.50), followed by the synthetic CB₁ agonist ACEA(SMD -3.15, 95%CI-4.75, -1.55) and synthetic CB₁/₂ agonist WIN55,212-2(SMD-1.74, 95%CI-2.81, -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 pre-clinical literature demonstrating the anti-inflammatory effects of cannabinoid drugs in inflammation of the gut. Larger randomised controlled-trials are warranted. Lippincott, Williams & Wilkins 2018-03-19 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/49221/1/IBD-D-17-00866_R1.pdf Couch, Daniel G., Maudslay, Henry, Doleman, Brett, Lund, Jonathan N. and O'Sullivan, Saoirse (2018) The use of cannabinoids in colitis: a systematic review and meta-analysis. Inflammatory Bowel Diseases, 24 (4). pp. 680-697. ISSN 1536-4844 cannabinoid inflammation gut intestine colitis https://academic.oup.com/ibdjournal/article/24/4/680/4944355 doi:10.1093/ibd/izy014 doi:10.1093/ibd/izy014
spellingShingle cannabinoid
inflammation
gut
intestine
colitis
Couch, Daniel G.
Maudslay, Henry
Doleman, Brett
Lund, Jonathan N.
O'Sullivan, Saoirse
The use of cannabinoids in colitis: a systematic review and meta-analysis
title The use of cannabinoids in colitis: a systematic review and meta-analysis
title_full The use of cannabinoids in colitis: a systematic review and meta-analysis
title_fullStr The use of cannabinoids in colitis: a systematic review and meta-analysis
title_full_unstemmed The use of cannabinoids in colitis: a systematic review and meta-analysis
title_short The use of cannabinoids in colitis: a systematic review and meta-analysis
title_sort use of cannabinoids in colitis: a systematic review and meta-analysis
topic cannabinoid
inflammation
gut
intestine
colitis
url https://eprints.nottingham.ac.uk/49221/
https://eprints.nottingham.ac.uk/49221/
https://eprints.nottingham.ac.uk/49221/