Abstracts

Rationale: Cannabidiol (CBD) likely has multiple anticonvulsant mechanisms of action, including reduction of excitatory glutamatergic transmission and facilitation of inhibitory GABAergic action. The aim of this study is to describe changes transcranial magnetic stimulation (TMS) measures of cortical excitability in patients with refractory epilepsy initiating treatment with CBD, and to determine the feasibility of using these measures as a biomarker of treatment response. Methods: Patients were enrolled in a PA State sponsored, open-label, compassionate use expanded access study of a pharmaceutical formulation of CBD (Epidiolex® provided by GW Research Ltd) as adjunctive therapy for treatment resistant epilepsy. Motor threshold (MT) and cortical excitability on recovery curve analysis were measured before and 4-8 weeks after starting CBD. Recovery curves were obtained with paired pulse TMS at short (2, 3, 5, 10, 15 ms) and long (150-250 ms) interstimulus intervals, in dominant hand. Results: Seven patients (4 male) were studied. Mean age was 11.7 years (range 6-15). Mean number of concomitant antiepileptic drugs was 2 (range 1-3). Five patients were not included in pre- and post-CBD recovery curve analysis because MT was higher than maximal machine output at baseline (n=2), or after CBD initiation (n=1), near maximal machine output (n=1), or because of excessive movement artifact (n=1). Cortical recovery curves were thus assessed in 2 participants (Figure 1, short interval recovery curve). MT increased with CBD treatment in all measurable participants (mean difference=12, p=0.03). Short and long interval recovery curves showed non-significant trends toward a decrease in cortical excitability. Conclusions: In this small sample of epilepsy patients, CBD had the following effects on measures of cortical excitability -- 1) increased motor threshold, a measure reflecting neuronal membrane excitability 2) increased SICI and LICI, measures associated with GABAergic effects. Application of these measures as a biomarker of response to treatment is limited by the prevalence of patients in this population who cannot be studied due to MT above maximal machine output. Funding: State of Pennsylvania