The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis
Couch et al.·Inflammatory Bowel DiseasesImpact 2.3
Klarer NutzenGRADEHoch66 Zitate
Stichprobek = 53 Studien
Dauerbis März 2017
KontrolleFahrzeugkontrolle
EndpunktDAI
Verblindungunklar
DesignSystematic Review + Meta-Analyse
”Kernaussage
Cannabinoide reduzierten Kolitis-Schweregrad (DAI) und Myeloperoxidase-Aktivität (MPO) in Tiermodellen signifikant im Vergleich zu Kontrolle.
Zusammenfassung
Systematische Review und Meta-Analyse zu Cannabinoiden bei intestinaler Inflammation; k=53 Publikationen (51 präklinische Tiermodelle, 2 klinische Studien). Präklinisch: Cannabinoide reduzierten Disease Activity Index (DAI) vs. Vehikel (SMD -1.36; 95% CI -1.62 bis -1.09; I²=61%); größter Effekt für FAAH-Inhibitor URB597 (SMD -4.43; 95% CI -6.32 bis -2.55). MPO-Reduktion SMD -1.26 (95% CI -1.54 bis -0.97; I²=48.1%). Cannabigerol zeigte größten MPO-Effekt (SMD -6.20; 95% CI -9.90 bis -2.50). Kein signifikanter Unterschied zwischen prophylaktischer und therapeutischer Anwendung.
OutcomeCannabinoide reduzierten DAI (SMD -1.36; 95% CI -1.62 bis -1.09; I²=61%) und MPO (SMD -1.26; 95% CI -1.54 bis -0.97; I²=48,1%) gegenüber Kontrolle
Vertrauen in die Evidenz
Sehr niedrigNiedrigModeratHoch
Hoch
Höchste von vier GRADE-Stufen, die Effektschätzung ist sehr verlässlich.
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.