Frequent cannabis use and the association with seizure burden in drug-resistant epilepsy.

Philibert-Rosas S.; Guston K.; Kalkach-Aparicio M.; Keller A.; Semia S.; Imhoff-Smith T.; Brace C.; Haworth S.; Branco de Paiva F.; Almane D. et al. · Epilepsia · 2026

**Background & Methods** This retrospective cohort study examined 64 adults with drug-resistant epilepsy admitted to a tertiary care epilepsy monitoring unit, comparing 22 frequent cannabis users (≥20 days/month) to 42 nonusers. Primary outcomes assessed epilepsy severity markers including time from onset to EMU admission, focal to bilateral tonic-clonic seizure (FBTCS) prevalence and frequency, and antiseizure medication (ASM) burden, with secondary analyses of epilepsy syndrome and brain imaging characteristics. **Key Findings** • Frequent cannabis use was associated with significantly shorter disease duration (mean 5.0 vs. 18.1 years to EMU admission, p=.004) and higher FBTCS prevalence (90.9% vs. 57.1%, p=.04), suggesting accelerated disease progression and greater seizure severity in cannabis users. • Frequent users demonstrated substantially higher annualized FBTCS frequency (3.00 vs. 1.32 seizures/year, p=.003) and greater ASM burden (mean 3.05 vs. 2.21 medications, p=.027), indicating more refractory seizure patterns requiring intensified pharmacological management. • All frequent cannabis users had temporal lobe epilepsy (TLE) localization, though this difference was not statistically significant between groups, and no significant imaging abnormalities distinguished the groups on volumetric analysis. **Dosage & Administration** Not reported. The study defined frequent use as cannabis use on ≥20 days per month but did not specify cannabinoid concentrations, consumption methods, or tetrahydrocannabinol (THC)/cannabidiol (CBD) ratios, though the authors noted modern products are characterized by high THC concentrations and variable composition. **Safety & Adverse Effects** Not reported. The study focused on association with seizure outcomes rather than adverse effects of cannabis use itself. **Evidence Quality** This retrospective cohort study provides low-to-moderate evidence limited by its small sample size (n=64), reliance on electronic medical record documentation without objective cannabis exposure measures, and selection bias inherent to EMU-admitted patients with treatment-resistant disease. The cross-sectional design precludes causal inference regarding cannabis effects on epilepsy severity. Authors acknowledge these limitations and call for prospective studies with objective biomarkers to clarify whether cannabis use directly worsens seizure outcomes or whether patients with more severe epilepsy are more likely to use cannabis.

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