Abstract
Objective: Controlled and open label trials have demonstrated efficacy of cannabidiol for certain epileptic encephalopathies. However, plant derived cannabidiol products have been used almost exclusively. Efficacy of synthetically derived cannabidiol has not been studied before. The objective of this study was to evaluate tolerability and efficacy of synthetic cannabidiol in patients with pharmacoresistant epilepsy.Methods: In this prospective, open-label study (DRKS00013177), patients with pharmacoresistant epilepsy received synthetic cannabidiol in addition to their previously stable anticonvulsive treatment. Starting dose was 5 mg/kg/day, up-titrated to a maximum of 50 mg/kg/day. Primary efficacy endpoint was monthly frequency of motor seizures at 3 months.Results: Between April 2017 and May 2019, 35 patients were enrolled in the study. Mean age was 19.7 years (SD 14.6). Median motor seizure frequency decreased from 21.8 (IQR 7.5–52.5) seizures per month at baseline to 8.5 (IQR 3.7–28.3, p < 0.001) at 3 months, effect not influenced by AED changes and drop-outs. Adjusted percentage reduction was 40.0% (IQR 18.2–58.5). Adverse events (AE) were reported in 25 patients (71.4%), most frequently somnolence (40%), diarrhea (34.3), and loss of appetite (20%). Two patients (5.7%) discontinued treatment due to AE. Median (range) of treatment duration was 321 days (range 36–824). With ongoing treatment up to date in 21 patients (60%).Conclusion: Efficacy and tolerance in our study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD. Regarding economic and ecological aspects, synthetic cannabidiol might be a reasonable alternative to plant derived cannabidiol.
Highlights
Over the last decade, the therapeutic use of cannabidiol (CBD) in intractable epilepsies has increased considerably [1]
Open label studies indicate that cannabidiol has anticonvulsive properties in a broader range of epilepsy syndromes and etiologies [6]
Patients with pharmacoresistant epilepsy as defined by the International League Against Epilepsy, medicated with at least one anticonvulsive drug (AED) at a stable dose for 4 weeks preintervention, stable ketogenic diet/vagal nerve stimulation device settings for at least 4 weeks pre-intervention and willingness of patients/caregivers to comply with seizure diary were eligible for inclusion
Summary
The therapeutic use of cannabidiol (CBD) in intractable epilepsies has increased considerably [1]. Open label studies indicate that cannabidiol has anticonvulsive properties in a broader range of epilepsy syndromes and etiologies [6]. Regardless of compositions, all studied preparations contain plant derived CBD [8]. The first pharmaceutical formulation of highly purified, plant derived CBD has been approved by the US Food and Drug Administration [9]. Single molecule cannabinoid drug development is a different approach where pharmaceuticalgrade synthetically derived substances are used [10]. Easier quality control, unlimited production possibilities and reduced environmental impact are advantages of synthetically derived cannabinoids and support further investigations of its therapeutic use. Besides one phase II study and one study using transdermal application, to our knowledge no studies using synthetic CBD in pharmacoresistant epilepsies have been published [12, 13]
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