Study register · detailKlinische Studie · Epilepsy · 2019
Higher cannabidiol plasma levels are associated with better seizure response following treatment with a pharmaceutical grade cannabidiol.
Szaflarski et al.·Epilepsy & behaviorImpact 2.4
Clear benefitGRADEModerate78 citations
Samplen = 100 Pat.
Durationunclear
EndpointSeizure frequency
Blindingoffen
DesignKlinische Studie
Cannabinoidcbd
Routeoral
”Key finding
Higher CBD plasma levels are associated with improved seizure control; an increase of 100 ng/mL was associated with a reduction of approximately 2 seizures per period.
Summary
Open-label EAP with Epidiolex® in treatment-refractory epilepsy (n=100; 56 adults, 44 children). Linear correlation between CBD dose (5–50 mg/kg/d) and plasma level (7,1–1200 ng/mL; r=0,640, p<0,001). Quantile regression: 100 ng/mL CBD increase associated with ~2 fewer seizures per 2-week period (1,87 [96%-CI 0,34–3,39]; p=0,018). Children and adults showed similar response rates; children possibly responsive at lower plasma levels.
P
PopulationAdults and children with treatment-refractory epilepsy in an expanded-access program, n=100 (56 adults, 44 children, 54 female)
I
InterventionPharmaceutically pure CBD (Epidiolex®), weight-based dosing 5–50 mg/kg/day orally, dose escalation possible every 2 weeks
O
OutcomeLinear relationship between CBD plasma levels and seizure reduction: +100 ng/mL CBD level associated with approx. 2 fewer seizures per 2-week period (β=1,87; 96%-CI 0,34–3,39; p=0,018)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Risk of bias
Quality profile
Sample size★★★★★
BlindingOpen-label
Effect sizeClear benefit
Citations / year★★★★★
Authors
Szaflarski JP, Hernando K, Bebin EM, Gaston TE, Grayson LE, Ampah SB, Moreadith R
Objective: The objective of this study was to determine the relationship between cannabidiol (CBD) dose, CBD plasma level, and seizure control in a large open-label single-center study.
Methods: All participants with treatment-refractory epilepsy participating in our expanded access program (EAP) were approached for participation. Highly purified grade CBD (Epidiolex(R)) dosing was weight-based and could be increased every 2 weeks by 5 mg/kg/day up to a maximum dosage of 50 mg/kg/day depending on tolerance and seizure control. Seizure counts were obtained at each visit with frequency calculated per 2-week periods. Cross-sectional plasma peak levels of CBD were obtained ~4 h after dosing in consecutively presenting patients.
Results: We evaluated 56 adults and 44 children (100 total; 54 female) at two time points - one before initiating CBD and one at the time of CBD plasma level testing. There was a positive linear correlation between CBD dosage (range from 5 to 50 mg/kg/day) and level (range from 7.1-1200 ng/mL) in all participants (r = 0.640; p < 0.001). The quantile regression model supported the notion of increased CBD levels being associated with improvement in seizure frequency after adjusting for age - specifically, a 100 ng/mL increase in CBD level was associated with approximately two counts reduction in seizure frequency per time period (1.87 96% confidence interval [CI] 0.34-3.39; p = 0.018). In participants with the same CBD level, differences in seizure improvement did not depend on age (p = 0.318).
Conclusions: In this open-label study, we found evidence of a linear correlation between CBD dosage and plasma levels, and that higher dose/levels are associated with a higher response rate for seizure improvement. Children and adults responded to CBD similarly. However, seizure control response rates suggest children may respond to lower dosages/plasma levels than adults. Findings reported in this study are specific to Epidiolex(R) and should not be extrapolated to other CBD products.