Cannabidiol reduces tuberous sclerosis complex-associated seizure frequency

Treatment with cannabidiol led to a significant reduction in the frequency of seizures in children and adults with tuberous sclerosis complex (TSC), according to the GWPCARE6* study.

This phase III, international, parallel-group, double-blind trial involved 224 patients (median age 11.4 years, 41.5 percent female) with TSC-associated seizures and medication-resistant epilepsy who were recruited from 46 sites in Australia, Poland, Spain, the Netherlands, UK, and US. Participants were randomly assigned to receive oral cannabidiol 25 mg/kg/day (CBD25; n=75) or 50 mg/kg/day (CBD50; n=73), or placebo (n=76) for 16 weeks. [JAMA Neurol 2020; doi:10.1001/jamaneurol.2020.4607]

At 16 weeks, patients who received either dose of cannabidiol had a greater reduction in seizure frequency from baseline than those who received placebo (-48.6 percent [for CBD25] and -47.5 percent [for CBD50] vs -26.5 percent).

The frequency of total seizures was also reduced in the cannabidiol arm vs the placebo arm (change from baseline, -48.1 percent [CBD25] and -47.6 percent [CBD50] vs -26.9 percent).

In addition, more patients treated with cannabidiol than placebo achieved a 50 percent reduction in the frequency of seizures from baseline (36.0 percent [CBD25] and 40.0 percent [CBD50] vs 22.0 percent).

Diarrhoea (31.0 and 56.0 percent for CBD25 and CBD50, respectively), somnolence (13.0 and 26.0 percent), and decreased appetite (20.0 and 23.0 percent) were the most common adverse events (AEs) reported in the cannabidiol group, with the incidence of AEs lower in the CBD25 than the CBD50 group.

In addition, elevated liver transaminase levels were reported in 18.9 percent of the patients in the cannabidiol group compared with none in the placebo group.

“This is the first randomized clinical trial to assess add-on cannabidiol in a disorder with primarily focal seizures, and the efficacy results are consistent with those from the four prior phase III trials of cannabidiol in the treatment of Lennox-Gastaut and Dravet syndromes,” the researchers noted. [JAMA Neurol 2020;77:613-621; Lancet 2018;391:1085-1096; N Engl J Med 2018;378:1888-1897; N Engl J Med 2017;376:2011-2020]

“In this study, both cannabidiol dosages were equally efficacious in reducing TSC–associated seizures compared with placebo, but the smaller dosage led to fewer AEs,” said the researchers.

“[L]ong-term evaluation of cannabidiol in patients with TSC is needed and will be conducted in the ongoing open-label extension trial,” they added.

*GWPCARE6: A randomized controlled trial of cannabidiol (GWP42003-P, CBD) for seizures in tuberous sclerosis complex