Abstract
Voltage-gated sodium channel genes are an important family of human epilepsy genes. De novo missense mutations in SCN8A (encoding Nav1.6) are associated with a spectrum of clinical presentation, including multiple seizure types, movement disorders, intellectual disability, and behavioral abnormalities such as autism. Patients with SCN8A mutations are often treated with multiple antiepileptic drugs, the most common being sodium channel blockers. Cannabidiol (CBD) has been included as a component of treatment regimens for some SCN8A patients; however, to date, there are no clinical trials that have evaluated the therapeutic potential of CBD in patients with SCN8A mutations. In the current manuscript, we demonstrated a dose-dependent increase in seizure resistance following CBD treatment in mice expressing the human SCN8A mutation R1620L (RL/+). We also found that CBD treatment improved social behavior and reduced hyperactivity in the RL/+ mutants. Our findings suggest that CBD may be beneficial in patients with SCN8A-associated disease.
Highlights
Cannabidiol (CBD), the predominant non-psychomimetic constituent of cannabis, was recently approved for the treatment of several forms of severe pediatric epilepsy, and there are currently ongoing clinical trials for the use of CBD in autism (Pretzsch et al, 2019; Aran et al, 2021) and schizophrenia (Leweke et al, 2012; Mcguire et al, 2018)
Since we observed the greatest protection with 360 mg/kg CBD, we evaluated whether this dose would protect against 6 Hz seizures when tested at twice the convulsive current (2×CC, 32 mA), which is used as a predictor of drugs that might protect against refractory seizures (Barton et al, 2001)
We investigated the therapeutic potential of CBD in RL/+ mutant mice
Summary
Cannabidiol (CBD), the predominant non-psychomimetic constituent of cannabis, was recently approved for the treatment of several forms of severe pediatric epilepsy, and there are currently ongoing clinical trials for the use of CBD in autism (Pretzsch et al, 2019; Aran et al, 2021) and schizophrenia (Leweke et al, 2012; Mcguire et al, 2018). CBD was recently approved by the FDA for use in three severe pediatric epilepsies, including DS where it was shown to significantly reduce spontaneous seizure frequency (Devinsky et al, 2016; Devinsky et al, 2017; Devinsky et al, 2019)
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