Abstracts

Rationale: There has been much recent interest in the use of cannabidiol (CBD) for treatment resistant epilepsy (TRE). Prior studies have focused on CBD use in several specific conditions, e.g. Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis. The New York State Department of Health has sponsored a compassionate use study involving a broader population of pediatric TRE patients. Here we present adverse events (AEs) reported on these patients and discuss possible interventions to address these AEs. Methods: This is a retrospective chart review of patients taking CBD for TRE at Montefiore Medical Center (MMC) as part of this compassionate use study. Patients are treated with GWP42003-P, a pharmaceutical formulation of CBD (100mg/ml) sesame oil oral solution provided by GW Research Ltd, at doses ranging from 5-35 mg per kg per day. Results: 18 patients were enrolled at MMC: 61% female, with median age 10.5 years (range 5-19). All but 1 reported improvement in seizure frequency. AEs were reported in 15 patients (83%). AEs noted in 2 or more patients are shown in Table 1. The dose of CBD per kg was not significantly different in those who had AEs vs. those who did not (median 20mg/kg/day in both groups).Interventions are shown in Table 2. Two of 9 patients with somnolence improved with decreased CBD dose (25% and 50% decrease respectively). One had persistent somnolence despite 20% decrease in CBD.  The remaining 6 patients with somnolence had mild symptoms that did not warrant intervention.Of 4 patients with diarrhea, 2 improved when CBD was given 3 times daily rather than twice (same total daily dose). One had improvement after CBD was stopped. One had spontaneous resolution of diarrhea.Of those with elevated liver function tests (LFTs), 3 of the 4 were on valproic acid (VPA). Two of these had normalization of LFTs after VPA was decreased (by 21% and 25% respectively); the 3rd patient’s LFTs normalized without intervention. One patient not on VPA had transient elevation in LFTs that resolved without intervention.  Conclusions: Prior studies have reported similar AEs including somnolence, GI disturbance, irritability / agitation, appetite changes, and convulsions1. Vomiting and ataxia, frequently reported in prior studies, were not present in our patients.Elevated LFTs were present in 22% of our patients, which is higher than other studies. In most cases this was noted in patients also taking VPA; a pharmacokinetic interaction between these medications has been proposed1. Decreased VPA dose led to improved LFTs. Decreased CBD led to improvement in 2 of the 3 patients requiring intervention for somnolence.Changing the CBD dosing from twice to three times daily, without changing total daily dose, led to improvement in 2 of 4 patients with diarrhea. To our knowledge this intervention for CBD associated diarrhea has not previously been reported.Reference: 1) O'Connell BK, Gloss D, Devinsky O. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav 2016 May;70:341-8 Funding: Funded by the New York State Department of Health