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

Academic Article

Abstract

  • © 2019 Elsevier Inc. 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.
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    Author List

  • Szaflarski JP; Hernando K; Bebin EM; Gaston TE; Grayson LE; Ampah SB; Moreadith R
  • Start Page

  • 131
  • End Page

  • 136
  • Volume

  • 95