“Background: Exogenous cannabinoids are considered promising therapeutic candidates for inflammatory bowel disease (IBD). However, robust pre-clinical evidence supporting its efficacy remains limited. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of exogenous cannabinoids in animal models of IBD.
Methods: Controlled experimental studies involving animal models of IBD that evaluated the effects of exogenous cannabinoids compared to untreated models were included. Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched up to August 26, 2025. Two independent reviewers conducted study selection, data extraction, and the risk-of-bias assessment. The risk-of-bias assessment was performed using the Systematic Review Center for Laboratory Animal Experimentation tool. Meta-analyses were performed using standardized mean differences (SMDs) and random-effects models. The study was registered in INPLASY (INPLASY202540009).
Results: Twenty-seven pre-clinical studies involving 408 animals were included. Compared with controls, exogenous cannabinoids significantly reduced disease activity index (SMD = -3.43; 95% confidence interval [CI]: -4.98 to -1.89; I2 = 83%) and histopathological score (SMD = -4.46; 95% CI: -6.37 to -2.54; I2 = 84%). It also decreased levels of myeloperoxidase (MPO), TNF-α, IL-6, and IL-1β. However, substantial heterogeneity was noted across several outcomes.
Interpretation: Exogenous cannabinoids show beneficial effects in pre-clinical IBD models, likely through anti-inflammatory, antioxidant, and barrier-enhancing mechanisms. These findings provide a supportive foundation for future translational research. Nevertheless, the overall certainty of the evidence is limited by unclear randomization, lack of blinding, high heterogeneity, and small sample sizes. Although some clinical trials have already begun exploring its therapeutic potential, further rigorous and standardized animal studies are needed to clarify mechanisms, optimize dosing, and reinforce the translational pathway.”