大麻素在结肠炎中的应用：系统评价和荟萃分析。

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

机构信息

School of Medicine, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom.

出版信息

Inflamm Bowel Dis. 2018 Mar 19;24(4):680-697. doi: 10.1093/ibd/izy014.

DOI:10.1093/ibd/izy014

PMID:29562280

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; 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.

摘要

背景

由于临床前文献表明大麻素类药物在减轻炎症方面具有疗效，因此预计会开展临床试验来研究大麻素类药物在治疗肠道炎症方面的应用。

方法

我们系统性地检索了有关靶向内源性大麻素系统药物治疗肠道炎症的益处的出版物。我们整理了截至 2017 年 3 月从 Embase、Medline 和 Pubmed 中检索到的可进行荟萃分析的研究结果。质量评估按照 mSTAIR 和 SRYCLE 评分标准进行。

结果

从 2008 篇论文中，我们确定了 51 篇关于大麻素化合物对鼠结肠炎影响的研究和 2 项临床研究。共评估了 71 个终点的 24 种化合物。植物大麻素大麻二酚是研究最多的药物。整个研究过程中均评估了宏观结肠炎严重程度（疾病活动指数 DAI）和髓过氧化物酶活性（MPO），并采用随机效应模型进行荟萃分析。与载体相比，大麻素降低了 DAI（标准均数差 SMD-1.36；95%置信区间，-1.62 至-1.09；I2=61%）。FAAH 抑制剂 URB597 的作用最大（SMD-4.43；95%置信区间，-6.32 至-2.55），其次是合成药物 AM1241（SMD-3.11；95%置信区间，-5.01 至-1.22）和内源性大麻素大麻酰胺（SMD-3.03；95%置信区间，-4.89 至-1.17；I2 未评估）。与载体相比，大麻素降低了啮齿动物的 MPO；SMD-1.26；95%置信区间，-1.54 至-0.97；I2=48.1%。大麻萜酚的作用最大（SMD-6.20；95%置信区间，-9.90 至-2.50），其次是合成的 CB1 激动剂 ACEA（SMD-3.15；95%置信区间，-4.75 至-1.55）和合成的 CB1/2 激动剂 WIN55，212-2（SMD-1.74；95%置信区间，-2.81 至-0.67；I2=57%）。我们未发现有报道偏倚的证据。在预防性和治疗性使用大麻素类药物方面，我们未发现有显著差异。