Cannabidiol in pediatric drug-resistant epilepsies: A systematic review and meta-analysis of seizure responder rates and neurobehavioral outcome reporting.

Praticò A. · Epilepsy research · 2026

**Background & Methods** This systematic review and meta-analysis examined cannabidiol (CBD) as adjunctive treatment for pediatric drug-resistant epilepsies, particularly developmental and epileptic encephalopathies like Dravet and Lennox-Gastaut syndromes. The analysis included 63 studies (92 reports; 3,439 patients) identified through PubMed/MEDLINE search through October 2026, with 37 studies (1,610 responders) included in meta-analysis using random-effects modeling. **Key Findings** - Pooled ≥50% seizure responder rate was 48.4% (95% CI 44.5-52.3) across all studies, with substantial heterogeneity (I²=76.4%). Responder rates differed significantly between study types: 41.3% in randomized controlled trials versus 49.8% in observational studies. - Long-term seizure outcomes demonstrated higher response rates (57.4%) compared to short-term assessments (42.8%), though long-term estimates were likely inflated by selective retention bias. - Critical evidence gap: cognitive and behavioral outcomes were reported in only 7.9% and 27.0% of studies, respectively, despite seizure outcomes being documented in 98.4% of studies. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This meta-analysis represents moderate-quality evidence with significant limitations. The majority of included studies (88.9%) were observational rather than randomized controlled trials, introducing substantial bias and heterogeneity. The prediction interval (29.4-67.8%) indicates wide variability in true effect estimates across populations. Responder rate differences between RCTs (41.3%) and observational studies (49.8%) suggest potential overestimation in non-controlled settings. The dramatic disparity in outcome reporting—with seizure metrics thoroughly documented but neurodevelopmental domains largely neglected—limits comprehensive clinical assessment. Long-term follow-up data likely reflect survivor bias due to selective retention of responders. Lack of standardized cognitive and behavioral measurement scales prevents meta-analysis of these domains. These findings underscore the need for future pediatric CBD research incorporating harmonized longitudinal follow-up, standardized neurodevelopmental outcome measures, and balanced reporting alongside seizure outcomes to enable robust efficacy and safety evaluation.

More recent cannabis research