Abstract
BACKGROUND: Ischemic stroke is an acute neurological disorder with limited treatment options. Medical cannabinoids (MCs), primary bioactive compounds extracted from cannabis plants, have shown therapeutic prospects for ischemic stroke. This study integrates bibliometrics and meta-analysis to comprehensively summarize the research landscape of MCs in cerebral ischemia and thoroughly investigate their role and potential mechanisms in ischemic stroke. METHODS: Bibliometric analysis was performed based on literature retrieved from Web of Science Core Collection (WoSCC), PubMed, and Scopus. For meta-analysis, a comprehensive search was conducted across four databases (WoSCC, PubMed, Embase, and Cochrane Library) and grey literature repositories. Studies were screened according to predefined criteria. Pooled standardized mean differences with 95% confidence interval were calculated, followed by subgroup analysis. RESULTS: A total of 241 publications were identified for bibliometric analysis. From 2000 to June 2025, the annual publication output on MCs in cerebral ischemia displayed a fluctuating yet overall upward trend. Keyword co-occurrence analysis revealed three major research topics: neuroprotective mechanisms of MCs, pathological models of cerebral ischemia, and bioactive components of MCs. Meta-analysis of 26 studies demonstrated that MCs provided significant neuroprotection in animal models of ischemic stroke, including cerebral infarct volume, neurological function score (NFS), cerebral blood flow (CBF), blood-brain barrier (BBB) permeability, brain water content, apoptosis (TUNEL-positive cells), oxidative stress markers, inflammation (TNF-α, IL-1β), and excitotoxicity (Glu/NAA, Lac/NAA ratio). Subgroup analysis revealed that intraperitoneal administration and a full-course of cannabidiol (CBD) treatment were associated with reduced heterogeneity and enhanced therapeutic benefit. Isoflurane was identified as a potentially suitable anesthetic. CONCLUSION: MCs exert multi-target neuroprotection in ischemic stroke by improving CBF, reducing brain edema and BBB permeability, and inhibiting oxidative stress, neuroinflammation, apoptosis, and excitotoxicity. Future research should focus on high-quality clinical trials to validate these findings and translate MCs into clinical practice. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/6je7n.