CBD gel reduces seizures in children with encephalopathies

Cannabidiol transdermal gel improved outcomes among children with developmental and epileptic encephalopathies, according to results of a nonrandomized controlled trial published in JAMA Network Open.

“Cannabidiol (CBD), the primary nonpsychoactive cannabinoid of the cannabis plant, reduces neuronal excitability and limits seizures through effects on multiple targets,” Ingrid E. Scheffer, MBBS, PhD, of Austin Health and Royal Children’s Hospital in Australia, and colleagues wrote. “An open-label trial of oral CBD suggested it was safe and well tolerated in patients with drug-resistant epilepsy. This was followed by randomized clinical trials enrolling patients with Dravet syndrome and [Lennox-Gastaut syndrome].”

According to the researchers, challenges remain for orally administered treatments among patients with developmental and epileptic encephalopathies, warranting consideration of alternative drug delivery methods.

In a study conducted at two centers in Australia and New Zealand between April 2018 and July 2019, Scheffer and colleagues sought to evaluate the safety and tolerability of CBD transdermal gel among 48 children (mean age, 10.5 years; 54% boys) in this patient population, as well as to evaluate seizure frequency, sleep and quality of life. They included children and adolescents aged 3 to 18 years with developmental and epileptic encephalopathies who were receiving a stable regiment of one to four antiseizure medications. Patients underwent 5.5 months of flexible-dosing maintenance following 1-month baseline and titration periods, totaling 6.5 months of treatment. The researchers analyzed data throughout the 6.5 months of treatment.

The intervention consisted of two applications per day of CBD transdermal gel at doses of 125 mg to 500 mg for the treatment period. Scheffer and colleagues conducted safety and tolerability assessments that included adverse events and examination of skin. Median percentage change from baseline in monthly seizure frequency of focal impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS) over 6.5 months served as the outcome for seizures.

Results showed 60% of participants had at least one treatment-related adverse event over 6.5 months, with 96% considered mild or moderate. Application-site dryness, application-site pain and somnolence were each reported by 8% of patients. One patient reported diarrhea, which was the only treatment-related gastrointestinal adverse event. CBD treatment correlated with reductions in FIAS and TCS (n = 33), with a median reduction in seizures of 58% at 5 months and 43.5% over the 6.5-month study period. Parent- and caregiver-reported improvements included social or interpersonal engagement and irritability (77%); alertness, energy and sleep (53%); and cognition or concentration (47%).

“These findings highlight the need for a double-masked randomized clinical trial of CBD transdermal gel,” Scheffer and colleagues wrote.