Several studies have assessed the efficacy, safety and tolerability of CBD in addition to drug therapies in children and young adults, with encouraging results.
Despite considerable progress in the pharmacological treatment of epilepsy in recent years, the disease and seizures cannot be properly controlled in about one third of patients even with the use of anti-epileptic drugs.
These refractory forms are associated with high morbidity and increased mortality, and the most effective treatment for achieving seizure control is surgery, for which, however, only a few patients are eligible.
There is, therefore, a need to develop new treatments for forms of epilepsy that are resistant to conventional drugs. Against this backdrop, cannabis-based medicinal products have aroused considerable interest: studies conducted in vivo and in vitro have shown anticonvulsant activity associated with cannabinoids, in particular cannabidiol (CBD), whose efficacy and safety in patients with resistant epilepsy, mainly children and young adults, have been assessed in a number of studies.
Safety and efficacy: a prospective study
The first study that collected prospective data on the use of CBD in patients with a drug-resistant form of epilepsy was conducted in the United States in 2014 [1].
This was an open-label trial that enrolled patients aged between 1 and 30 years with severe resistant epilepsy with onset in childhood, who, before entering the study, had been treated with stable doses of antiepileptic drugs. The selected patients were included in an expanded-access programme involving 11 centres.
Study participants received CBD orally at a dosage of 2-5 mg/kg per day until intolerance or a maximum dose of 25-50 mg/kg per day, depending on the centre, was reached.
The safety and tolerability of the treatment were assessed, as well as the median percentage change in monthly mean seizure frequency at 12 weeks.
In total there were 214 participants, of whom 162 (76%) were considered for the safety analysis as 12-week follow-up data were available; 137 patients were included in the efficacy analysis. In both groups, the gender distribution was balanced and the average age was 10.5 years; the most common forms of epilepsy were Dravet syndrome (20% and 23%) and Lennox-Gastaut syndrome (19% and 22%).
In the group analysed for safety, adverse events were recorded in 79% of the patients (128 patients): the most frequent were drowsiness (41 patients, 25%), reduced appetite (31 patients, 19%), diarrhoea (31 patients, 19%), fatigue (21 patients, 13%) and seizures (18 patients, 11%), but only in 5 cases (3%) was treatment discontinued. Severe adverse events were reported in 48 patients (30%); in 20 cases (12%), a correlation with CBD treatment was considered possible.
The results in the efficacy analysis group indicated an average frequency of 15.8 focal motor seizures per month during the 12 weeks of treatment compared to the baseline value of 30, with a median monthly frequency reduction of 36.5%.
According to the study authors, cannabidiol could, therefore, reduce seizure frequency and appears to have an adequate safety profile in children and young adults with highly drug-resistant epilepsy.
Confirmation from real-life data
Two recent papers investigated the safety and efficacy of cannabinoids in the treatment of drug-resistant epilepsy in a real-life setting.
In a retrospective analysis conducted by Israeli researchers, the clinical data of 139 children and young adults aged between 2 and 29 years (median age: 12 years), treated with purified CBD between 2018 and 2022 in 5 centres in Israel [2] were analysed. The median dose of purified CBD was 12.5 mg/kg, and the median treatment duration 9 months.
The most frequent diagnoses in the treated patients were Lennox-Gastaut syndrome (52 patients, 37.4%), refractory epilepsy (41 patients, 29.5%), Dravet syndrome (23 patients, 16.5%) and tuberous sclerosis (23 patients, 16.5%).
Following treatment, a high percentage of patients (92.2%) experienced a reduction in the frequency of seizures, which in 41% of cases exceeded 50%. In 38% of the patients, the treatment also had positive effects such as improved vigilance and language skills and the achievement of new developmental milestones.
The researchers also conducted a statistical analysis to identify any predictive factors for the reduction of seizure frequency. The data showed that previous treatment with CBD oil may foster a decrease in seizures while taking purified CBD, while age, developmental stage, diagnosis, dose of purified CBD and concomitant treatment with anticonvulsants do not affect the reduction in seizure frequency.
Regarding safety, adverse events were recorded in 39 patients (28.1%); the most common were irritability (20.9% of patients) and drowsiness (12.9%).
According to Israeli researchers, therefore, purified CBD is well tolerated and may be effective as an additional therapy in daily clinical practice in paediatric and young adult patients with epilepsy of different aetiologies.
Lastly, in a third paper, a group of British researchers analysed data from the UK Medical Cannabis Registry to assess the response to cannabis-based medicinal products in children in terms of seizure frequency reduction and safety [3].
Data from 35 paediatric patients with drug-resistant epilepsy, predominantly male (57%) and with a mean age of 9.7 years, were included in the analysis.
The diagnosis was Lennox-Gastaut syndrome for 5 patients, Dravet syndrome for 2 and other syndrome for one patient; for 9 patients epilepsy had a genetic cause, while for 14 the aetiology was idiopathic or unknown.
Treatments with medicinal cannabis products included isolated (19 patients) or broad-spectrum CBD oil (17 patients), or combinations of CBD and THC (17 patients).
The median follow-up was 12 months.
With regard to seizure frequency, 23 patients (65.7%) experienced a reduction of at least 50% from baseline; 13 (37.1%) achieved a reduction of 90% or more and 4 (11.4%) achieved complete remission.
In the group treated with CBD and THC in combination, 16 patients (94.1%) had a 50% reduction in seizure frequency, compared to 31.6% (6 patients) in the group treated with isolated CBD and 17.6% (3 patients) in the group treated with broad-spectrum CBD, with a statistically significant difference.
From a safety point of view, 26 adverse events affecting 16 patients were recorded, in most cases mild (12 patients) or moderate (10 patients), and without significant differences between the various treatments.
The authors conclude that, despite all the limitations of such a study, the results provide promising indications for the treatment of drug-resistant epilepsy in children with cannabis-based medicinal products.
Reference
- Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8.
- Tzadok M, Gur-Pollack R, Florh H, et al. Real-life experience with purified cannabidiol treatment for refractory epilepsy: a multicenter retrospective study. Pediatr Neurol. 2024 Jan;150:91-96.
- Erridge S, Holvey C, Coomber R, et al. Clinical outcome data of children treated with cannabis-based medicinal products for treatment resistant epilepsy-Analysis from the UK Medical Cannabis Registry. Neuropediatrics. 2023 Jun;54(3):174-181.
