Devinsky, E. Marsh, D. Friedman, E. Thiele, L. Laux, J. Sullivan, I. Miller, R. Flamini, A. Wilfong, F. Filloux, M. Wong, N. Tilton, P. Bruno, J. Bluvstein, J. Hedlund, R. Kamens, J. Maclean, S. Nangia, N. S. Singhal, C. A. Wilson, A. Patel, M. R. Cilio
- CBD oil treatment showed a favorable safety and adverse event profile
- There was a 36.5% reduction in motor seizures frequency over the treatment period and a reduction of 35.5% in seizures of all types
- For motor seizures, 39% of patients had a reduction of 50% or more, 21% of 70% or more and 9% had a reduction of 90% or more
- For all seizure types, 37% of patients had a reduction of 50% or more, 22% of 70% or more, and 8% had a reduction of 90% or more
- Most patients who achieved seizure freedom or a reduction of 90% had never experienced a previous antiepileptic drug regimen that was as efficacious as CBD oil
OBJECTIVES & HYPOTHESIS → The aim was to establish whether addition of cannabidiol to existing anti-epileptic regimens would be safe, tolerated, and efficacious in children and young adults with highly treatment-resistant epilepsy. The primary endpoint was to demonstrate safety and tolerability while the efficacy outcome was measured by the median percentage change in the mean monthly frequency of motor seizures and in all seizure types at 12 weeks. The response rate was also assessed, defined as patients whose reduction in seizure frequency was > 50%, 70%, or 90%.
METHODS → Prospective, open-label, expanded-access trial with patients aged 1–30 years with severe, intractable, treatment-resistant epilepsy. Of the 214 enrolled patients, 162 were included in the safety analysis and 137 in the efficacy one. There was a 4 week pre-cannabidiol period during which the seizure activity was reported and after which patients received a 99% pure oil-based cannabidiol extract in a 100mg/mL sesame oil-based solution. Cannabidiol at a dose of 2–5 mg/kg/day divided in twice-daily dosing was added to the baseline antiepileptic drug regimen, then up-titrated until intolerance or a maximum daily dose of 25 mg/kg or 50 mg/kg was reached.
RESULTS → The high rates of seizure reduction and freedom achieved suggest clinically meaningful efficacy. Patients included in this study were some of the most treatment-resistant and poor-prognosis patients, with high rates of use of rescue medication and sudden unexpected death.
Safety outcomes: Adverse events were reported in 128 patients and most of them were mild-moderate and transient. The safety and tolerability of cannabidiol was acceptable and its adverse event profile favorable, with only 3% of patients stopping treatment because of an adverse event. Efficacy outcomes: The median monthly frequency of motor seizures decreased from 30.0 to 15.8 over the treatment period and the median change in monthly motor seizures was –36.5%. 5 patients were free of all motor seizures during the 12 week treatment period. 54 patients had a reduction of 50% or more in motor seizures, whereas 29 had a reduction of 70% or more and 12 of 90% or more. For all seizure types, 51 patients had a reduction of 50% or more, 30 of 70% or more, and 11 had a reduction of 90% or more. The median change in monthly seizures of all types was –35.5%.