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

Background

Cannabidiol (CBD) has emerged as an important adjunctive treatment option for pediatric drug-resistant epilepsies (DREs), particularly in developmental and epileptic encephalopathies (DEEs) such as Dravet syndrome and Lennox-Gastaut syndrome. However, the current literature remains heterogeneous and predominantly focused on seizure outcomes, with limited evaluation of broader neurodevelopmental domains.

Methods

A systematic review with meta-analysis of proportions was conducted according to PRISMA 2020 recommendations. PubMed/MEDLINE was searched for studies evaluating CBD treatment in pediatric epilepsies (search updated to October 1st 2026), supplemented by citation searching. Randomized controlled trials and observational studies were included; secondary reports of the same cohort (extensions, post hoc and sub-analyses) were linked to their parent study. Extracted variables included study design, epilepsy syndrome, follow-up duration, seizure outcomes, cognitive outcomes, and behavioral outcomes. The primary outcome was the proportion of patients achieving ≥ 50% seizure reduction at the earliest stable post-titration timepoint, pooled across all studies with ≥ 10 assessed patients using a random-effects model (logit transformation, DerSimonian-Laird estimator).

Results

Sixty-three studies (92 reports) were included, predominantly observational (56/63, 88.9%). The meta-analysis included 37 studies (3439 assessed patients; 1610 responders) and yielded a pooled ≥ 50% responder rate of 48.4% (95% CI 44.5-52.3), with substantial heterogeneity (I²=76.4%; 95% prediction interval 29.4-67.8%). Responder rates were lower in the CBD arms of randomized trials (41.3%) than in observational studies (49.8%), and higher at long-term than at short-term assessments (57.4% vs 42.8%). Seizure outcomes were reported in 98.4% of included studies, whereas cognitive and behavioral outcomes were reported in only 7.9% and 27.0% of studies, respectively.

Conclusions

Approximately half of children with drug-resistant epilepsies treated with adjunctive cannabidiol achieve a ≥ 50% seizure reduction in the available, predominantly observational literature; randomized trials suggest a somewhat lower proportion, and long-term estimates are likely inflated by selective retention. The literature remains strongly seizure-centered, while cognitive and behavioral outcomes are inconsistently assessed and poorly standardized. Future pediatric CBD studies should incorporate harmonized longitudinal follow-up and standardized neurodevelopmental outcome measures alongside seizure outcomes.