Expanding the Evidence for Cannabidiol in Focal Epilepsy

A multicenter study led by Nationwide Children’s Hospital demonstrates long-term efficacy and safety of Epidiolex® for treatment-resistant seizures.

As global use of cannabidiol for seizure management increases, most research has targeted generalized epilepsy. This leaves a major evidence gap for patients with focal seizures and epilepsy.

Anup D. Patel, MD, FAAN, FAES, FCNS, neurologist and associate chief quality officer in the Center for Clinical Excellence at Nationwide Children’s Hospital, and colleagues across the nation recently published a landmark study in Epilepsia evaluating the long-term safety and efficacy of Epidiolex® in patients with treatment-resistant focal epilepsies through the U.S. Expanded Access Program.

Epidiolex is a purified plant-based cannabidiol oil. It is FDA-approved for seizures associated with Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. This new study provides the most extensive long-term data to date on the sustained benefit of cannabidiol for other types of focal epilepsy.

The research tracked 140 patients whose seizures persisted despite multiple anti-seizure treatments. Participants received care at 35 epilepsy centers in the United States, including 26 pediatric patients at Nationwide Children’s.

“This was truly a collaborative effort,” Dr. Patel, who is also a professor in Clinical Pediatrics and Neurology at The Ohio State University, says. “Working together, we wanted to eliminate treatment silos, standardize outcomes and build the evidence needed to inform how we treat focal epilepsy.”

Within the patient pool, 33 had tuberous sclerosis complex-related focal epilepsy. The remaining 107 had other focal epilepsies, such as cortical dysplasia and frontal lobe epilepsy. All participants received 100 mg/mL oral cannabidiol, starting at 2–10 mg/kg and titrated to 25–50 mg/kg per day.

During a 144-week follow-up, researchers observed that cannabidiol treatment led to a 46% to 87% drop in focal seizure frequency, depending on the epilepsy type. Total seizure frequency also showed similar reductions.

“Seeing sustained seizure reduction over nearly three years is remarkable,” Dr. Patel explains. “Many of these patients have tried multiple therapies without success.”

In addition, the rate of seizure freedom was small but clinically meaningful, at about 3% of participants.

The most common side effects included diarrhea, somnolence and appetite suppression. In some patients, occasional mild elevations in liver enzymes required monitoring.

“Overall, cannabidiol was well tolerated,” Dr. Patel notes. “But, careful observation is important, especially early in treatment.”

The research also holds historical significance.

“When we began studying cannabidiol in 2014, the federal government classified it as a Schedule I substance with no recognized medical benefit,” he recalls. “We’ve come a long way from navigating complex licensing just to provide it to patients.”

This study supplies the strongest evidence yet that cannabidiol could play a key role in managing focal epilepsies.

Dr. Patel explains, “The expanded access program is critical in collecting real-world data that can inform the gold-standard, placebo-controlled trials leading to further FDA approvals.”

Although the study’s open-label design lacked a control group, Dr. Patel maintains the results are clinically meaningful.

“These results suggest cannabidiol can offer long-term seizure reduction and a known tolerable safety profile,” he concludes. “We can now make more informed choices for patients with focal epilepsy who have exhausted other treatments.”

Reference:

Patel AD, Szaflarski JP, Lyons PD, et al. Long-term efficacy and safety of cannabidiol in patients with treatment-resistant focal epilepsies treated in the Expanded Access Program. Epilepsia. Published online July 17, 2025. doi:10.1111/epi.18496.

Image Credit: Adobe Stock (header); Nationwide Children’s Hospital (portrait)