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. In this scope, one particularly promising candidate is ibogaine, a psychoactive alkaloid present in Tabernanthe iboga root bark that consistently reduces opioid withdrawal symptoms, and in many cases promotes abstinence in individuals addicted to opioids, cocaine and alcohol.

Based on these data, we performed a study to assess ibogaine’s efficacy in a model of alcohol dependence that is predominantly driven by negative reinforcement. In this model, Wistar rats undergo chronic intermittent alcohol vapor exposure for 14 h/day over the period of 7 weeks; as a result, animals reach clinically relevant blood alcohol levels, develop physical withdrawal signs and long-lasting neuroadaptations. Before and after the vapor exposure, rats are trained in daily 30 min operant sessions to self-administer 10% ethanol coupled with orange smell serving as odor cue. To test for compulsivity in alcohol intake, 10% solution is adulterated with quinine, making it highly aversive and thus hindering its rewarding properties for animals. To assess the persistence of addiction memory, rats are subjected to one week of extinction training in the absence of odor cue and alcohol reward, after which two sessions of cue-induced reinstatement are performed. We administered ibogaine 24h before quinine-adulterated alcohol self-administration sessions and cue-induced reinstatement and assessed motivation for reward in both tests. Ibogaine significantly reduced alcohol self-administration in taste aversion test and motivation for obtaining reward in cue-induced reinstatement, suggesting a long-lasting effect on addiction memory. We conclude that ibogaine demonstrates promising results in our model of alcohol addiction that warrant further research into its mechanism of action and translational potential for use in pharmacotherapy.