Background: Recent data shows superior efficacy of cannabidiol in comparison with the known anti-seizure medications, with a dramatic improvement in seizure control and favorable safety and efficacy. The analgesic efficacy of cannabinoids progressively decreases during repeated usage. Nevertheless, current literature is scares of information concerning tolerance to cannabidiol treatment in epilepsy.

Aim: to assess the tolerance rate of cannabidiol in the treatment of epilepsy in the pediatric population.

Methods: a Prospective review of 92 consecutive patients aged 1-37 years (mean-11.8 years) with treatment-resistant epilepsy who were treated with Cannabis oil extract (CBD/THC ratio of 20:1) during the period of 1.3.2014 to 31.9.2017. Tolerance was defined as either the necessity to increase dose by 30% or more following reduction of efficacy, or response reduction of more than 30%.

Results: Ninety-two patients with treatment-resistant epilepsy of various etiologies were treated with Cannabis oil extract for an average of 19.8 months. Tolerance was observed in 30 (32.6%) of the patients, on an average dose of 12.6 mg/kg/d. Mean duration to tolerance appearance was 7.3 months (range: 1-24 months). 17 of the 30 patients with tolerance (58%) showed > 50% reduction in mean monthly seizure frequency at baseline. Increasing CBD dose led to achieving pervious anti-seizure efficacy in 40% of patients (12/30), and satisfying but less than prior response level in 15 patients (50%).

Conclusions: Cannabidiol tolerance exists, which limits the efficacy of this antiseizure treatment in the long-term clinical management of refractory epilepsy in both pediatric and adult patients.