Total funding applied for: 40.000,00 €

Scientific Abstract of the Project

Alcohol use disorders create the largest health burden globally. Current pharmacological treatment Call f approaches have limited effectiveness. Very recently, clinical benefits of the hallucinogen psilocybin for the treatment of alcohol addicted patients have been provided and experiments in alcohol addicted rats suggest that it can block relapse behavior in the long-run. Here we wish to study the mode of action of psilocybin on the behavioral and epigenetic system levels. In the first work package, we will evaluate the behavioral mechanisms that underlie the effects of psilocybin on relapse drinking in rats. Here we will address the following questions: Does psilocybin interfere with baseline alcohol consumption? Does psilocybin interfere with cue and/or stress-induced alcohol-seeking (craving)? Does psilocybin reduce the motivation to drink alcohol? Does psilocybin produce alcohol-specific effects; i.e., does it also interfere with natural reward processing? Does psilocybin alter taste perception? Does psilocybin produce sexspecific effects? Therefore, the first aim of our proposal is to test the behavioral mechanisms of the longlasting efficacy of psilocybin in male and female subjects on relapse behavior.

Many studies on psilocybin in humans describe very long-lasting positive effects on disease trajectories and quality of life. How can such long-lasting effects be explained? Epigenetic effects occur as one possible candidate mechanism. Here we propose together with our Co-PI to study genome-wide alterations in methylation and transcription in a longitudinal fashion in alcohol addicted rats following a single application of psilocybin. Therefore, the second aim of our proposal is to provide translational information on the epigenetic and transcriptional levels to understand the neurobiological underpinnings and mode of action of psilocybin in the alcohol addicted brain.

Lay Abstract

Nearly 60 million EU citizens engage in harmful drinking and 23 million Europeans are suffering from alcohol addiction. Approved pharmacological treatments for alcoholism are limited in their effectiveness, and new drugs that can be translated into the clinic are warranted. Here we will test the efficacy of psilocybin for treating alcohol addiction and will study the underlying neurobiological (i.e., epigenetic) mechanism.