Perampanel Treatment of Alcohol Use Disorder

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This project aims to meet the urgent need for developing better medications to treat alcohol use disorder (AUD), a major public health problem. The proposed study will test perampanel, a recently FDA approved anticonvulsant medication, to determine its clinical usefulness in treating alcoholism via an “alcohol challenge” paradigm paired with a small pilot clinical trial. Human alcohol challenge laboratory studies are an efficient and affordable way to screen medications for their usefulness in alcoholism treatment prior to performing a larger clinical trial. In this paradigm, subjects are given the medication perampanel (at either a high dose, low dose, or placebo dose, on subsequent challenge days), and then are administered intravenous ethanol to see if the medication reduces the rewarding and reinforcing effects of alcohol. The proposed study would be the first experiment in a line of research developing perampanel as a treatment for AUD. We will also conduct a very small open-label pilot study of the medication to explore efficacy and feasibility of perampanel treatment in a sample of subjects with AUD. Perampanel works primarily as a selective, non-competitive glutamatergic AMPA receptor antagonist, a property that makes it quite unique in the neuropharmacologic armamentarium. Preclinical research in animal models of alcoholism and other addictions suggests that AMPA receptor antagonists reduce drinking and relapse to addictive drugs. If perampanel proves to reduce the rewarding and reinforcing effects of alcohol in humans, and reduces drinking in the pilot study, it would provide a strong rationale for more definitive clinical trials with this medication.