Cannabidiol Tolerance in Children and Adults With Treatment-Resistant Epilepsy

Authors: Shimrit Uliel-Sibony, Tel-Aviv Sourasky Medical Center, Dana Children's Hospital; Moran Hausman-Kedem, Tel-Aviv Sourasky Medical Center, Dana Children's Hospital; and Uri Kramer, Tel-Aviv Sourasky Medical Center, Dana Children's Hospital

Content: Rationale: The aim of this study is to assess the tolerance rate of cannabinoids in the treatment of epilepsy in the pediatric and adults population. Methods: Prospective review of the tolerance to cannabinoids of 92 consecutive patients aged 1-37 years (mean11.8 years) with treatment-resistant epilepsy during the period of 1.3.2014 to 31.9.2017. Tolerance was defined as either the necessity to increase dose in 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 (CBD/THC ratio of 20:1) for an average of 19.8 months. Tolerance was seen in 30 (32.6%) of the patients. It was reported on an average dose of 12.6 mg/kg/d and the mean time till appearance of tolerance was 7.3 months (range: 1-24 months). Out of these patients 58% (17 patients) showed > 50% reduction in mean monthly seizure frequency. While trying to resist the tolerance effect, CBD dose was increased in most patients with observed tolerance. This led to achieving pervious response level in 12 and satisfying but less than prior response level in 15 patients. Of the patients with observed tolerance, in nine it was concomitant with drug's tapering. Conclusions: Our findings suggest that cannabidiol tolerance exists and it limits the efficacy of this antiseizure treatment in the long-term clinical management of epilepsy in the pediatric and adults population Funding: No funding was received.