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 Δ
9
-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
ss, 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. C
SS, Min
plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. C
SS, 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, C
SS, 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.
We hypothesized that enteral doxapram would effectively treat apnea of prematurity without the appearance of major side effects. Of 16 infants, 10 (BW 1,520 ± 102 g) received doxapram alone and 6 (BW 1,020 ± 35 g) received doxapram plus theophylline. Apneas decreased from 16.7 ± 1.9 to 2.1 ± 0.6 in infants receiving doxapram alone, and from 38.2 ± 4.4 to 7.9 ± 2.2 apneas/24 h in those receiving doxapram plus theophylline. This was associated with an increase in alveolar ventilation, a shift of the ventilatory response to CO2 to the left, and no change in the immediate ventilatory response to 100% oxygen. Side effects included premature teeth buds corresponding to the lower central incisors, prevalence of occult blood in stool and necrotizing enterocolitis. The findings suggest that doxapram effectively controls apnea when given enterally, but should be used cautiously because of potentially harmful side effects.
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