“Introduction: Stroke is a leading cause of morbidity and mortality worldwide, with ischemic stroke accounting for the majority of cases. The endocannabinoid system (ECS), comprising cannabinoid receptors CB1 and CB2, has been implicated in regulating physiological processes and has shown potential neuroprotective effects in preclinical studies. However, the precise impact of cannabinoid receptor modulation on stroke outcomes remains unclear. This systematic review and meta-analysis aimed to evaluate the impact of cannabinoid receptor modulation on infarct volume and behavioral deficits in animal models of focal ischemic stroke, with a primary focus on infarct outcomes.
Method: A comprehensive literature search was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, yielding 29 eligible studies for inclusion.
Results: The analysis revealed significant reductions in infarct volume with cannabinoid agonists, particularly CB1 and CB2 agonists, indicating their potential as neuroprotective agents. Subgroup analyses further highlighted specific agonists, such as ACEA and KN38-72717, as particularly effective in reducing infarct volume. Additionally, CB antagonists, particularly CB1 antagonists, such as SR141716, showed promising results in reducing infarct volume. Although improvements in neurological scores were observed with both agonists and antagonists, statistical significance was not reached, indicating the need for further investigation.
Conclusion: These results highlight the potential of cannabinoid receptor modulation as a neuroprotective strategy in ischemic strokes and underscore the need for further research to elucidate the underlying mechanisms and optimize therapeutic approaches.”