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Front Neurol. 2019 Jul 3;10:716. doi: 10.3389/fneur.2019.00716. eCollection 2019.

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study.

Author information

1
Cannabinoid Research Initiative of Saskatchewan, University of Saskatchewan, Saskatoon, SK, Canada.
2
Department of Pediatrics, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
3
Division of Child Neurology, Department of Pediatrics, Loma Linda University, San Bernardino, CA, United States.
4
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.
5
Saskatchewan Health Authority and Department of Psychology, University of Saskatchewan, Royal University Hospital, Saskatoon, SK, Canada.
6
Clinical Trial Support Unit, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
7
Department of Pathology and Laboratory Medicine, Royal University Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada.
8
Cell Signalling Laboratory, Departments of Psychiatry and Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
9
Department of Pharmaceutical Services, Royal University Hospital, Saskatchewan Health Authority, Saskatoon, SK, Canada.
10
Division of Neurology, Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
11
Division of Pediatric Neurology, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
12
Division of Pediatric Neurology, Department of Pediatrics, Children's Hospital, University of Manitoba, Winnipeg, MB, Canada.
13
Service de Neurologie Pédiatrique, Département de Neurosciences, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC, Canada.

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 non-linear 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.

KEYWORDS:

cannabidiol; cannabinoid plasma levels; cannabis; epileptic encephalopathy; Δ9-tetrahydrocannabinol

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