What is the role of cannabidiol (Epidiolex) in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

The FDA approved a purified formulation of cannabidiol (Epidiolex) in June 2018 for seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients aged 2 years or older. Cannabidiol is a structurally novel anticonvulsant and the exact mechanism by which it produces anticonvulsant effects is unknown. It does not appear to exert its anticonvulsant effects through CB1 receptors, nor through voltage-gated sodium channels.

Approval was based on results from several studies that compared adding cannabidiol added to conventional AEDs to placebo and the incidence of drop seizures from baseline. An international study of 225 patients with LGS (mean patient age 15 years) were randomized to receive cannabidiol 20 mg/kg/day or 10 mg/kg/day, or placebo over 14 weeks. During the 4-week baseline period, the median number of drop seizures was 85 in all groups combined. The median reduction from baseline in drop-seizure frequency per 28 days during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg group, and 17.2% in the placebo group. During treatment, 30 patients (39%) in the 20-mg group, 26 (36%) in the 10-mg group, and 11 (14%) in the placebo group had at least a 50% reduction from baseline in drop-seizure frequency. The odds ratio (OR) for 20 mg vs placebo was 3.85 (95% CI, 1.75 - 8.47; P < 0.001) and the OR for 10 mg vs placebo was 3.27 (95% CI, 1.47 - 7.26; P = 0.003). [93]

A study (n=171) conducted in 24 clinical sites in the United States, the Netherlands, and Poland showed a median percentage reduction in monthly drop seizure frequency from baseline was 43.9% (IQR -69.6 to -1.9) in the cannabidiol group and 21.8% (IQR -45.7 to 1.7) in the placebo group. The estimated median difference between the treatment groups was -17.21 (p = 0.0135) during the 14-week treatment period. [94]

A double-blind, placebo controlled study found that investigated cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome found that the median frequency of convulsive seizures per month decreased from 12.4 to 5.9 win the cannabidiol group compared to a decrease from 14.9 to 14.1 in the placebo group. The adverse events that were more frequent in the cannabidiol group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function test. [95]

Systemic exposure and adverse effects of cannabinol are dose-related. An open-label safety study by Gaston et al on the interactions between common antiepileptic drugs and the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) reported that with increasing doses of cannabidiol, increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam serum levels were seen (all p < 0.01). The study also found that in adults, increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) were seen. Also of note was higher levels of AST/ALT in those who are also taking valproate. All changes were within the accepted therapeutic range. [96, 97]


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