This study aims to characterize outcomes in children and adults being treated for epilepsy with cannabidiol (CBD) and ketogenic diet therapy (KDT) concurrently. 

Cannabidiol was approved by the FDA in 2018 for the treatment of Lennox-Gastaut Syndrome, Dravet Syndrome, and Tuberous Sclerosis Complex. Additionally, there are artisanal CBD/THC products available. KDT is a nonpharmacologic treatment for refractory epilepsy. Even though CBD and KDT are used for many of the same indications, there currently exists no research that characterizes the interactions between these two treatments. 

Fifty-eight patients (mean age 10 years at combination initiation) were identified from 2018-2025. The average duration of combination therapy was 17.4 months. Forty-four (76%) patients received prescription CBD and 35 (60%) were on the classic ketogenic diet; 33 (57%) received CBD before starting KDT. At 1 month, 40% had >50% seizure reduction; at 3 months, 28% had >50% seizure reduction. Overall, 87% reported moderate-large urinary ketosis, and for those who added CBD to KDT, 8/13 had no change in ketosis. Five (15%) with documented liver function tests before and after the combination had increased values, mostly minor. Eighteen (36%) had weight loss.  Younger patients were more likely to start the classic KD, be treated with prescription cannabidiol, and not lose weight. There was greater seizure reduction when CBD was initiated before KDT. 

This study is the first to characterize outcomes and tolerability in patients being treated with CBD and KDT concurrently for refractory epilepsy. The combination was well-tolerated and these results show similar efficacy of the combination in treating epilepsy compared to either therapy alone.