Cannabidiol was used increasingly over the last 5 years in the therapy of epilepsy and has shown to be effective in reducing seizures in patients with Dravet syndrome, Lennox–Gastaut syndrome, and tuberous sclerosis complex. Nevertheless, studies on the effect of cannabidiol on interictal epileptiform discharges (IED) was sparse and largely limited to small studies. Furthermore, there was no publication to date that reports the effect of cannabidiol on sleep structures in patients with epilepsy.
To evaluate the influence of cannabidiol on interictal epileptiform activity and sleep architecture in a cohort of children with drug-resistant epilepsy.
Patients (age 3 months to 18 years) with drug-resistant epilepsy were prospectively followed from November 2019 to January 2021 during an open-label trial of cannabidiol. Oral administration of cannabidiol was given at a starting dose of 5 mg/kg/day, followed by gradual increase up to 20 mg/kg/day (to a maximum of 50 mg/kg/day) over 14 days; with concomitant antiepileptic medication. Electroencephalograms (EEG) were recorded prior to (T0) and after 3 months (T1) of cannabidiol therapy, and the evaluation was analysed by two independent raters, blinded to any clinical information. IEDs were visually identified and rates per minute were calculated. Improvement of sleep architecture was recorded if sleep structures were seen at second EEG (T1) that were not present at the first EEG (T0).
Three months of cannabidiol therapy (T1) resulted in significantly lower IED rate as compared to baseline (T0) in children with drug-resistant epilepsy (36.8 ± 27.2 vs. 19.6 ± 19.5). Nevertheless, the rate of IED reduction does not positively correlate with the reduced frequency of seizure. No significant difference in the mean percentage of IED reductions was observed between responders (>50% reduction of seizure frequency) and non-responders. Notably, sleep had improved in 84.6% of patients treated with cannabidiol for 3 months (initial record of abnormal sleep: 56%).
There is a wide acceptance and evidence that both IED and sleep have an impact on the cognitive functioning of patients with epilepsy. Based on results obtained from this study, future research should focus on whether reduced IED and improved sleep microstructure after cannabidiol therapy may enhance cognitive function. The studies should include larger and more homogeneous cohort. Furthermore, an automated and standardised EEG analysis based on a uniform EEG protocol should be introduced to mitigate potential biases.
This is the first prospective study that demonstrated the efficacy of cannabidiol therapy in reducing IEDs and improving sleep microstructure in children with drug-resistant epilepsy.