Study register · detailOpen-Label-Pilotstudie (prospektiv, Dosiseskalation) · Epilepsy · 2019
Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study.
All participants showed a reduction in seizure frequency as well as improved quality-of-life scores under CHE dose escalation with good tolerability.
Summary
n=7 children with treatment-resistant epileptic encephalopathy; cannabis herbal extract (THC:CBD 1:20) up to 10–12 mg CBD/kg/day; all participants showed improvement in seizure frequency and QOLCE quality-of-life scores; C_ss-CBD levels at >50% seizure reduction were below values previously reported for purified CBD; recommended starting dose 5–6 mg CBD/kg/day.
P
PopulationChildren with treatment-resistant epileptic encephalopathy, n=7
I
InterventionCannabis Herbal Extract (CHE) 1:20 THC:CBD, dose escalation up to 10–12 mg CBD/kg/day, oral
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OutcomeAll 7 participants tolerated CHE up to 10–12 mg CBD/kg/day; all showed improvement in seizure frequency and QOLCE scores; CBD plasma levels for >50% seizure reduction lower than for purified CBD
Confidence in the evidence
Very lowLowModerateHigh
Low
The second of four GRADE levels, the effect estimate is of limited reliability.
Downgraded for
Risk of biasImprecision
Quality profile
Sample size★★★★★
BlindingOpen-label
Effect sizeClear benefit
Citations / year★★★★★
Authors
Huntsman RJ, Tang-Wai R, Alcorn J, Vuong S, Acton B, Corley S, Laprairie R, Lyon AW, Meier S, Mousseau DD, Newmeyer D, Prosser-Loose E, Seifert B, Tellez-Zenteno J, Huh L, Leung E, Major P.
<b>Purpose:</b> 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. <b>Methods:</b> The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a <i>Cannabis</i> Herbal Extract (CHE) preparation of 1:20 Δ<sup>9</sup>-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 (C<sub>ss, Min</sub>) of selected cannabinoids were quantified. <b>Results:</b> All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. C<sub>SS, Min</sub> plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. C<sub>SS, Min</sub> CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, C<sub>SS, Min</sub> levels of THC remained lower than what would be expected to cause intoxication. <b>Conclusion:</b> 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.