Use of purified cannabidiol as add-on therapy in children with non-self-limited focal epilepsies of childhood: A multicenter study.

Reyes Valenzuela G.; Espeche A.; Fortini S.; Gamboni B.; Adi J.; Semprino M.; Fasulo L.; Galicchio S.; Cachia P.; Chacón S. et al. · Epilepsy & behavior : E&B · 2026

**Background & Methods** This multicenter retrospective study evaluated the long-term effectiveness and tolerability of adjunctive purified cannabidiol (CBD) in 79 children with treatment-resistant non-self-limited focal epilepsies (non-SeLFEs) across 11 pediatric neurology centers in Argentina and Chile. All participants had previously failed ≥4 antiseizure medications (ASMs), with individualized CBD dosing based on response and tolerability over a mean follow-up period of 30 months (range, 6-44 months). **Key Findings** • 54.4% of patients (43/79) achieved ≥50% seizure frequency reduction, with 5.1% (4/79) becoming seizure-free; response remained stable through 30 months of follow-up. • Response rates did not significantly differ between tuberous sclerosis complex (TSC) and non-TSC focal epilepsies, and no significant associations were found between seizure reduction and seizure type, age at onset, epilepsy duration, or concomitant ASM use. • Interictal epileptiform abnormalities improved among responder patients, indicating electrographic benefit alongside clinical improvement. **Dosage & Administration** Mean purified CBD dose was 34 mg/kg/day (range, 10-40 mg/kg/day), individualized according to patient response and tolerability. **Safety & Adverse Effects** Adverse events occurred in 23 patients (29.1%), predominantly mild and transient in nature. Drowsiness was the most common adverse effect. Most adverse events were manageable through dose adjustments. No serious treatment-related adverse events were reported during the study period. **Evidence Quality** This study is limited by its retrospective design, which restricts causal inference and introduces potential recall bias. The lack of a control group prevents comparison of CBD efficacy against standard care or placebo. The relatively small sample size (n=79) and heterogeneous population (various focal epilepsy etiologies) may limit generalizability. However, the multicenter design across two countries strengthens external validity, and the prolonged follow-up period (up to 44 months) provides valuable data on long-term tolerability and sustained efficacy. The study provides Level III-IV evidence and serves as preliminary evidence supporting further randomized controlled trials of purified CBD in treatment-resistant childhood focal epilepsies.

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