Frequent cannabis use may be associated with markers of increased epilepsy severity among patients with drug-resistant epilepsy.
Investigators conducted a retrospective cohort study of adults with drug-resistant epilepsy admitted to a single academic tertiary epilepsy monitoring unit between 2019 and 2024. Drug-resistant epilepsy was defined as failure of adequate trials of 2 appropriately chosen and tolerated antiseizure medications. Among 100 patients screened, 64 met the final inclusion criteria, 22 of whom reported frequent cannabis use and 42 of whom had no documented cannabis use. Patients reporting occasional use were excluded. The cohort consisted entirely of patients with focal epilepsy.
Cannabis exposure was determined retrospectively from electronic medical records during the year prior to admission rather than through a standardized survey or objective testing. Frequent use was defined as at least 20 days of use per month. The investigators assessed time from epilepsy onset to epilepsy monitoring unit admission, the presence and annualized frequency of focal to bilateral tonic–clonic seizures (FBTCS), and antiseizure medication (ASM) burden at discharge. Additional analyses examined epilepsy syndrome and mesial temporal imaging measures.
FBTCS were documented in 91% of frequent cannabis users compared with 57% of nonusers. Mean annualized FBTCS frequency was also higher among frequent users, at 3 vs. 1.32. In contrast, the investigators found no statistically significant differences in the presence or frequency of focal aware seizures or focal impaired awareness seizures.
Frequent cannabis users also reached epilepsy monitoring unit evaluation sooner following epilepsy onset, with a mean interval of 5 years vs. 18.1 years among nonusers. At discharge, frequent users were taking a mean of 3.05 ASMs compared with 2.21 among nonusers. ASM burden at admission did not differ between groups, but frequent users had a larger mean increase in medications during monitoring.
All 22 frequent cannabis users had temporal lobe epilepsy compared with 83% of nonusers, although the between-group difference was not statistically significant following correction for multiple comparisons. In the analysis restricted to 57 patients with temporal lobe epilepsy, frequent users had a shorter mean interval from epilepsy onset to monitoring unit admission (5 vs. 17.3 years), a higher prevalence of FBTCS (91% vs. 54%), greater mean annualized FBTCS frequency (3 vs. 1.02), and greater ASM burden at discharge (3.05 vs. 2.26).
Exploratory imaging analyses did not identify statistically significant between-group differences in hippocampal or amygdala volumes after correction for multiple comparisons. Among patients with left-sided mesial temporal lobe epilepsy confirmed by stereoelectroencephalography, frequent users had larger left amygdala volumes, but the difference did not remain statistically significant following correction. No statistically significant volumetric differences were identified in the right-sided subgroup.
The timing of cannabis initiation was available for 15 of the 22 frequent users, and cannabis use preceded reported seizure onset in all 15. However, the investigators characterized analyses of the interval between cannabis initiation and seizure onset as descriptive and hypothesis-generating because of the small subgroups and reliance on self-reported timing.
The study had several limitations. Cannabis exposure was derived from clinical documentation and was not objectively verified, and information on tetrahydrocannabinol content, dose, route, amount consumed, and duration of use was not consistently available. Patients classified as nonusers could have included patients whose cannabis use was undocumented. The retrospective design precluded causal inference, and seizure frequency was largely based on patient or caregiver reports. Psychiatric and behavioral comorbidities were not systematically quantified or adjusted for, creating the possibility of residual confounding. The single-center cohort was also limited to patients with drug-resistant focal epilepsy and was predominantly White and non-Hispanic, limiting generalizability to broader epilepsy populations.
“Although causality cannot be inferred, these findings suggest that cannabis exposure may be an important factor to consider in the clinical evaluation and management of patients with drug-resistant epilepsy,” wrote lead study author Santiago Philibert-Rosas, of Washington University in St. Louis, and colleagues.
The study authors reported no conflicts of interest.
Source: Epilepsia
