Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

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.

Cannabidiol for Treating Lennox-Gastaut Syndrome and Dravet Syndrome in Korea

“…This positive response was lower than the 36%–57% positive response within 6 months shown previously by studies that did not distinguish between the patient groups. 7 8 17 …”

“…In rare cases, serious adverse events occur that may require hospital admission for treatment, such as status epilepticus or extrapyramidal symptoms. 7 8 20 However, in the case of status epilepticus, the causal relationship with CBD is unclear because most enrolled patients were those with refractory epilepsy, such as LGS or DS. In our study, similar to others, the adverse events reported included high rates of GI problems, such as diarrhea and inadequate appetite, which can be expected, as the current formulation of CBD in use is in the form of an oil.…”

“…This affects the metabolism of some antiepileptic drugs; in the case of CLB, it can increase the serum level of N-desmethylclobazam, which is an active metabolite of CLB. 8 21 22 23 24 …”

“…Mild adverse events such as somnolence and gastrointestinal (GI) symptoms have been reported. 7 8 9 10 After randomized trials assessing CBD use in LGS and DS were conducted, the United States Food and Drug Administration approved the prescription of CBD for both epileptic encephalopathies in 2018. 11 12…”

Cannabidiol in the Treatment of Epilepsy: A Focused Review of Evidence and Gaps

“…Although an FDA-approved, pharmaceutical-grade, high-purity CBD is available (Epidiolex R ) (42, 43), its cost is prohibitive for some patients. A synthetic CBD may be a solution to legal obstacles and costs (50).…”