Two CBD Doses Reduced Dravet Convulsive Seizures Without Showing More Benefit at the Higher Dose
Both tested CBD doses reduced convulsive seizures beyond placebo in a Dravet syndrome trial. The higher dose did not show greater average efficacy, and several tolerability concerns were more frequent with it.
A defined pediatric population
The blinded randomized trial studied children and adolescents with treatment-resistant Dravet syndrome receiving other antiseizure treatment. Of 199 randomized patients, 198 contributed to the intention-to-treat analysis.
Purified oral CBD at 10 or 20 mg/kg/day was compared with placebo over a 14-week treatment period. The primary endpoint was convulsive seizure frequency, not elimination of epilepsy or efficacy of retail supplements.
Baseline reductions are not placebo-adjusted effects
Estimated convulsive seizure reductions from baseline were 48.7% with the lower dose, 45.7% with the higher dose and 26.9% with placebo. Both CBD comparisons significantly favored active treatment.
These percentages differ from the model-based reductions relative to placebo. Relabeling them casually misrepresents the treatment effect. Similar average efficacy does not demonstrate formal dose equivalence or identical individual benefit.
Tolerability changes the interpretation
Decreased appetite, diarrhea, fatigue and several other adverse outcomes occurred more frequently with the higher dose. Liver-enzyme elevations greater than three times the reference limit occurred in CBD-treated patients taking valproate; none occurred with placebo.
Safety-analysis group sizes differed from randomized efficacy groups because two patients titrated above their assigned target. Those denominators should not be mixed when reporting percentages. Concurrent medication and somnolence also mattered.
Do not generalize beyond the formulation
These findings concern adjunctive purified CBD in Dravet syndrome. They do not establish dosing for another condition or show that more CBD always provides more benefit.
The observation period was limited, caregiver seizure records were important and concurrent treatment complicates interpretation. A later correction changed a collaborator’s name, rather than the efficacy results.
For a different study design, see our analysis of adult epilepsy CBD outcomes, retention and confounding.
Primary research
Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome: A Randomized Clinical Trial. JAMA Neurology (2020). DOI: 10.1001/jamaneurol.2020.0073.
