Antiseizure effect of cannabidiol seen within 2 weeks of treatment

In the treatment of patients with drug-resistant epilepsy associated with tuberous sclerosis complex (TSC), the antiseizure effect of cannabidiol (CBD) occurs within 6–10 days, according to the results of a phase III trial. Adverse events (AEs) also emerge during the first 2 weeks of the titration period, and majority of these are resolved during the 16-week treatment period.

A total of 224 patients (median age 11.3 years) with treatment-resistant TSC-related epilepsy were randomized to receive plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25, n=75) or 50 mg/kg/day (CBD50, n=73) or placebo (n=76) for 16 weeks (4-week titration, 12-week maintenance).

Treatment was initiated at 5 mg/kg/day for all groups and reached 25 mg/kg/day at day 9 and 50 mg/kg/day at day 29. Researchers calculated percentage change from baseline in TSC-associated seizure (countable focal or generalized) count by cumulative day (ie, including all previous days). Time to onset and resolution of AEs were evaluated.

Overall, patients had discontinued a median of four antiseizure medications and were currently taking three. Seizure reduction between CBD and placebo differed by day 6 (titrated dose, 15 mg/kg/day) and became nominally significant (p<0.049) by day 10. The difference in ≥50-percent responder rate between placebo and CBD was also observed by day 10.

In 61 percent of the population, AEs occurred during the first 2 weeks of the titration period (CBD25, 61 percent; CBD50, 67 percent; placebo, 54 percent). The AEs resolved within 4 weeks of onset in 42 percent of patients on placebo and 27 percent of those on CBD, and by end of trial in 78 percent of those on placebo and 51 percent of those on CBD.

While the CBD treatment effect occurred within 2 weeks of starting treatment, the findings also showed that the percentage reduction in seizure count and the proportion of ≥50-percent responders continued to increase over the full treatment period of the trial. This suggested that some patients without an early response might still benefit later during the treatment.