Abstract
Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5-6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible nonlinear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.
| Original language | English |
|---|---|
| Article number | 716 |
| Journal | Frontiers in Neurology |
| Volume | 10 |
| Issue number | JUL |
| DOIs | |
| Publication status | Published - 2019 |
| Externally published | Yes |
Bibliographical note
Funding Information:This study was funded through research grants from the Saskatchewan Health Research Foundation, the Jim Pattison Children’s Hospital Foundation, the Durwood Seafoot Estate, and the Savoy Foundation. As grant numbers were not provided with these awards, copies of the award letters from these granting agencies to our research team are available upon request. The granting agencies and CanniMed, from whom we purchased the study drug at cost, had no influence on study design, or the collection, interpretation, and/or reporting of data.
Funding Information:
The authors would like to acknowledge the financial support to perform this study received from the Jim Pattison Children’s Hospital Foundation, the Durwood Seafoot Estate, the Saskatchewan Health Research Foundation and the Savoy Foundation. We also acknowledge the operational support provided by the Department of Pediatrics, University of Saskatchewan and the Saskatchewan Health Authority.
Publisher Copyright:
Copyright © 2019 Huntsman, Tang-Wai, Alcorn, Vuong, Acton, Corley, Laprairie, Lyon, Meier, Mousseau, Newmeyer, Prosser-Loose, Seifert, Tellez-Zenteno, Huh, Leung and Major. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
ASJC Scopus Subject Areas
- Neurology
- Clinical Neurology
PubMed: MeSH publication types
- Journal Article