Abstract

Alcohol addiction, characterized by a compulsive desire to drink alcohol despite knowledge or evidence of its harmful consequences, affects about 23 million Europeans and creates a large health burden worldwide. Although substantial research has been done into possible therapies, currently available pharmacological treatments including disulfiram, naltrexone and acamprosate demonstrate limited efficacy. Recent resurgence of interest in psychedelic research holds promise for further investigating the potential of these drugs to treat different psychiatric disorders including addictions. Early studies with psychedelics showed promising results in the treatment of alcohol addiction, a finding which was recently confirmed in a meta‐analysis. In this light, the aim of our study was to assess the efficacy and safety of R‐ketamine and psilocybin in a unique DSM‐5‐based model of alcohol addiction. In this model, single‐housed rats are given free access to water and 3 different concentrations of alcohol﴾5%, 10% and 20%﴿ and are allowed to drink for 8 weeks, after which the alcohol bottles are withdrawn for 2 weeks and reintroduced at the end of this deprivation phase. This cycle of drinking/deprivation continues for extended period of time ﴾8 months﴿,during which animals develop compulsive drinking behavior that is characterized by a significant increase in alcohol consumption right after the end of deprivation ﴾alcohol deprivation effect﴿. We administered R‐ketamine and psilocybin in a model‐specific dosing schedule to determine their impact on alcohol relapse behavior measured by alcohol deprivation effect in male and female Wistar rats. Both compounds were found to significantly reduce alcohol intake in male and female rats following deprivation with varying degrees, thereby decreasing the pronounced ADE that is usually observed in this model. We conclude that R‐ketamine and psilocybin demonstrate promising results in our model of alcohol relapse that warrant further research into their mechanism of action and translational potential for use in alcohol addiction.