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

Abstract Objective Cannabis use has increased substantially, with modern products characterized by high tetrahydrocannabinol concentrations and variable composition. The relationship between frequent cannabis use and epilepsy outcomes remains uncertain. We examined the association between frequent cannabis use and epilepsy severity, clinical phenotype, and imaging characteristics in patients admitted to an epilepsy monitoring unit (EMU). Methods This retrospective cohort study included adults with drug‐resistant epilepsy admitted to a tertiary care EMU. Patients were classified based on cannabis use documented in the electronic medical record over the year prior to admission. Frequent use was defined as cannabis use on ≥20 days/month; patients with low use were excluded. Primary outcomes included markers of epilepsy severity, including time from epilepsy onset to EMU admission, presence and frequency of focal to bilateral tonic–clonic seizures (FBTCS), and antiseizure medication (ASM) burden. Secondary analyses evaluated epilepsy syndrome and mesial temporal lobe volumetric measures. Results Sixty‐four patients were included (42 nonusers and 22 frequent users). Frequent cannabis use was associated with shorter time from epilepsy onset to EMU admission (mean [SD] = 5.0 [4.2] vs. 18.1 [16.3] years, p = .004), higher prevalence of FBTCS (90.9% vs. 57.1%, p = .04), greater annualized FBTCS frequency (mean [SD] = 3.00 [3.63] vs. 1.32 [3.87], p = .003), and higher ASM burden (mean [SD] = 3.05 [1.00] vs. 2.21 [1.14], p = .027). All frequent cannabis users had temporal lobe epilepsy (TLE), although the between‐group difference in TLE prevalence was not statistically significant. No significant group differences were observed in imaging analysis. Significance In this cohort of patients with drug‐resistant epilepsy, frequent cannabis use was associated with markers of increased epilepsy severity, including higher FBTCS burden, shorter time to specialized EMU evaluation, and greater ASM requirements. Prospective studies using objective cannabis exposure measures are needed to clarify the relationship between cannabis use and epilepsy outcomes.