Frequent Cannabis Use Tied to Greater Seizure Burden in DRE

Frequent cannabis use in patients with drug-resistant epilepsy (DRE) experienced more severe seizures and required more antiseizure medications (ASMs) than their counterparts who did not use cannabis.Results of a small retrospective study of 64 adults with DRE showed those who used cannabis at least 20 d/mo had focal to bilateral tonic-clonic seizures (FBTCSs) — which start in one area of the brain and spread to cause full-body convulsions — were much more common than in nonusers (90.9% vs 57.1%).Frequent cannabis users also had more FBTCSs each year, averaging 3.00 vs 1.32 per year among nonusers, despite being treated with more ASMs.“Right now, the honest answer when a patient asks whether their cannabis use is affecting their seizures is that we’re not sure,” study investigator Santiago Philibert-Rosas, MD, research specialist at Washington University Medicine in St. Louis, said in a statement. “Larger studies will help us give them a real answer — how much matters and whether stopping helps — so they can make an informed decision.”The study was published online on September 28 in Epilepsia.More Use, Increased PotencyCannabis use is common among US adults, with about 15% reporting use in the past month and nearly 8% using it daily or nearly daily. In addition, recreational cannabis products increasingly contain high concentrations of tetrahydrocannabinol (THC) and relatively little cannabidiol.However, the relationship between cannabis use and seizure control remains unclear because previous studies often relied on self-reported use and lacked detailed data about dose, frequency, and THC content.To address this gap, investigators assessed the relationship between frequent cannabis use and epilepsy severity, clinical phenotype, and brain imaging findings in adults with DRE.The investigators reviewed 100 adults admitted to an epilepsy monitoring unit (EMU) at a tertiary care academic center from 2019 to 2024. The final cohort included 64 adults with DRE. Of these individuals, 22 were frequent cannabis users and 42 were nonusers.Frequent use was defined as using cannabis at least 20 d/mo. Nonusers had no documented history or mention of cannabis use. The study did not consistently capture product type, THC concentration, dose, route of administration, amount used per session, or duration of use.All participants had focal epilepsy and met the International League Against Epilepsy definition of DRE, having failed to achieve sustained seizure freedom despite adequate trials of at least two appropriate, well-tolerated ASMs.The groups were similar in age at seizure onset and EMU admission. The mean age at seizure onset was 25.7 years among frequent cannabis users and 22.0 years among nonusers.Greater Seizure SeverityFrequent cannabis users reached EMU evaluation sooner after epilepsy onset than nonusers (mean, 5.0 vs 18.1 years; P = .004). The most pronounced differences involved FBTCSs, reported in 90.9% of frequent users compared with 57.1% of nonusers (P = .04). Frequent users also experienced more FBTCSs annually (mean, 3.00 vs 1.32; P = .003).Other focal seizure measures were similar between groups, including focal aware seizures (54.5% vs 52.4%) and focal impaired awareness seizures (95.5% vs 85.7%).At discharge from the EMU, participants who were frequent cannabis users were taking more ASMs, 3.05 vs 2.21 among nonusers (P = .027).Temporary lobe epilepsy (TLE) was diagnosed in all 22 frequent cannabis users and 35 of 42 nonusers (100% vs 83.3%). However, the difference was not statistically significant after correction for multiple comparisons, including seizure burden, medication use, and epilepsy classification (adjusted P = .16).Among the 57 participants with TLE, frequent cannabis use was associated with a shorter interval from seizure onset to EMU admission (5.0 vs 17.3 years; P = .01), a higher prevalence of FBTCSs (90.9% vs 54.3%; P = .02), and greater ASM use at discharge (3.05 vs 2.26 medications; P = .028).MRI analyses showed no significant differences in hippocampal or amygdala volumes after accounting for the multiple comparisons.Among the 15 participants who recalled when they began using cannabis, all said their use started before their seizures did. However, the researchers cautioned, however, that the subgroup was small and relied on self-report, so the finding does not establish a causal link.Frequent cannabis use may be linked to more difficult-to-treat epilepsy, said senior investigator Aaron F. Struck, MD, associate professor of neurology at Washington University Medicine.“This result is maybe the most concerning,” he told Medscape Medical News. “Chronic THC users had more frequent severe seizures despite being on more antiseizure medications.”Struck suggested that clinicians ask patients about regular cannabis use and consider whether reducing or stopping it might improve seizure control.One potential explanation for this correlation involves the endocannabinoid system, particularly CB1 receptors, which are concentrated in the hippocampus and other mesial temporal structures, Struck noted.“We hypothesize that it is the interaction of the CB1 receptors, where THC binds, and their density in the mesial temporal structures, primarily the hippocampus,” that accounts for the association with TLE.The hippocampus is already prone to epileptogenesis, and THC may affect this region in particular. “The observation is that THC could make mesial temporal lobe epilepsy more severe and difficult to treat,” he said, but emphasized that the mechanism remains speculative.A Bi-Directional Link?The need for a cautious interpretation was reinforced by Orrin Devinsky, MD, professor of neurology, neurosurgery, and psychiatry at NYU Grossman School of Medicine in New York City, who was not involved in the study.“Without a prospective and randomized study, which is near impossible in this case, it is hard to separate cannabis use from confounding issues such as depression, anxiety, insomnia, and impulsivity,” Devinsky, who also directs the NYU Langone Comprehensive Epilepsy Center, told Medscape Medical News.“The arrows could point both ways,” he said, adding that people with more severe epilepsy may also be more likely to use cannabis.Patients may also use cannabis because they believe it helps with sleep, anxiety, or pain, but those conditions themselves may adversely affect seizures, Devinsky said. High-THC cannabis could also potentially worsen seizures directly, impair sleep, or cause memory problems that affect medication adherence.For these reasons, Devinsky recommended closely monitoring patients with epilepsy who use high-THC products, ideally documenting seizure patterns for at least 3 months before they start cannabis and for an equal or longer period afterward.Disclosure information for study authors is available in the original study publication. Devinsky reported no relevant financial disclosures.