Study: CBD Linked to Major Seizure Reductions in Those With Severe, Drug-Resistant Epilepsy Across Genetic and Acquired Causes

A new study published in the journal Medicine by researchers from Korea University College of Medicine provides further evidence that cannabidiol (CBD) can substantially reduce seizures in children and young adults with some of the most difficult-to-treat forms of epilepsy, even when the condition stems from a wide variety of genetic, structural, and acquired causes. The retrospective cohort study examined 29 patients with pediatric-onset, intractable epilepsy treated with adjunctive CBD therapy at Korea University Hospitals over a five-year period. Patients had seizure onset at a median age of just 7 months, were taking a median of five antiseizure medications, and many had already tried ketogenic diets, vagus nerve stimulation, or even brain surgery before CBD was introduced.

At the start of CBD therapy, 93.1% were on valproic acid, 82.8% were on clobazam, and 75.9% were on levetiracetam.

Despite this heavy treatment burden, CBD was associated with striking improvements.

At 12 months, 79.3% of patients experienced at least a 50% reduction in seizures, and 34.5% experienced a reduction of at least 75% without generalized motor seizures. One patient with a GABRB3 genetic variant became completely seizure-free.

The study reports that “CBD therapy demonstrated favorable retention, efficacy, and safety profiles in pediatric-onset intractable epilepsy across a spectrum of etiologies.”

Importantly, these outcomes were sustained. The retention rate — a key indicator of whether patients and doctors find a treatment worthwhile — was 92.3% at 6 months, 86.9% at 12 months, and 86.3% at 24 months.

Researchers emphasized that many patients required careful adjustments to their other antiseizure medications after starting CBD, particularly clobazam and valproic acid, to manage side effects like somnolence and lethargy. These side effects were generally mild and resolved with dosage adjustments rather than stopping CBD.

“Adverse events occurred in 37.9%, most commonly somnolence and lethargy. These were mild and resolved with antiseizure medication adjustments,” the authors wrote.

Only three patients discontinued CBD, due to pneumonia, severe lethargy, or worsening seizures.

The patient population reflected the complexity of real-world pediatric epilepsy. Confirmed genetic causes included SCN1A, SCN2A, GABRB3, KCNT1, KIF1A, COL4A1, Angelman syndrome, and Down syndrome. Others had cortical dysplasia, hemimegalencephaly, brain injury from lack of oxygen, or infections of the central nervous system. In 41.4% of cases, the cause was unknown, though most of those patients had a history of infantile spasms.

The researchers noted that CBD’s broad mechanisms of action may explain why it worked across such diverse conditions.

“CBD lacks psychoactive effects and exerts its antiepileptic actions through several complex mechanisms,” the study explains, including modulation of the endocannabinoid system, reduction of neuroinflammation, suppression of excitatory neurotransmitter release, and regulation of calcium and adenosine signaling.

The authors said these “multifactorial mechanisms of CBD may underlie its efficacy across a diverse range of epileptic syndromes.”

One of the most notable findings involved the GABRB3 genetic variant, where a patient achieved seizure freedom. The study highlights that this gene affects GABA receptors in the brain and that CBD may positively influence this pathway, though researchers caution that more data is needed before drawing firm conclusions about variant-specific responses.

The study also sheds light on the interaction between CBD and clobazam. CBD is known to increase levels of clobazam’s active metabolite in the body, which may enhance seizure control but also increase sedation. Rather than discontinuing CBD, physicians in the study often reduced clobazam or other medications to improve tolerability — a strategy the authors believe contributed to the unusually high long-term retention rates seen in this group.

“Active modification of concomitant ASMs may have contributed to the low discontinuation rate of CBD,” the authors wrote, noting that this rate was significantly lower than seen in previous CBD studies.

The researchers acknowledge limitations, including the small sample size and reliance on caregiver seizure reports, but say the findings add to a growing body of evidence showing CBD’s usefulness beyond the specific syndromes for which it is officially approved.

“CBD demonstrated additive antiseizure properties across diverse etiologies,” they concluded. “With appropriate adjustment of concomitant antiseizure medications, CBD may be safely utilized across both genetic and nongenetic causes of intractable pediatric epilepsy.”

For families dealing with severe childhood epilepsy that has not responded to years of medications, dietary therapies, and even surgery, this study offers encouraging evidence that CBD may provide meaningful seizure relief across a surprisingly wide range of underlying causes — with manageable side effects and strong long-term adherence.