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Epilepsy Behav. 2019 Jun;95:131-136. doi: 10.1016/j.yebeh.2019.03.042. Epub 2019 Apr 29.

Higher cannabidiol plasma levels are associated with better seizure response following treatment with a pharmaceutical grade cannabidiol.

Author information

1
Department of Neurology, University of Alabama at Birmingham, USA; Department of Pediatrics, University of Alabama at Birmingham, USA; UAB Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA; Serina Therapeutics, Inc., Huntsville, AL, USA. Electronic address: jszaflarski@uabmc.edu.
2
Department of Neurology, University of Alabama at Birmingham, USA; UAB Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA.
3
Department of Neurology, University of Alabama at Birmingham, USA; Department of Pediatrics, University of Alabama at Birmingham, USA; UAB Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA.
4
Biostatistics, Birmingham, AL, USA.

Abstract

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®) 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® and should not be extrapolated to other CBD products.

KEYWORDS:

Cannabidiol; Epidiolex®; Epilepsy; Level; Seizure control

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