Effects of the monoamine stabilizer (-)OSU6162 on cognitive function in alcohol dependence

INTRODUCTION: Alcohol dependence (AD) is associated with a dysregulated mesolimbocortical dopamine system—a pathway which is also implicated in both reward and cognition. The monoamine stabilizer (-)-OSU6162 (OSU) is a novel pharmacological compound with the ability to reduce ethanol intake and ethanol seeking in long-term drinking rats as well as reducing alcohol craving in AD patients. Dopaminergic drugs can both impair and improve cognitive functions, and the aim of the current study was to investigate the effect of OSU treatment on cognitive functioning in AD patients. METHOD: In a randomized double-blind placebo-controlled study, 56 individuals with AD received 14 days of OSU or placebo treatment. Neuropsychological tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB®) and other tasks were used to evaluate treatment effect on executive function/impulsivity, working memory, attention, emotional recognition, and divergent thinking. RESULTS: Treatment with OSU did not impair neuropsychological function in any of the cognitive domains investigated (all p > 0.1). In fact, OSU treatment did, compared to placebo, improve future planning ability (F((1,46)) = 6.9; p = 0.012; Cohen’s d = 0.54), verbal divergent thinking (F((1,44)) = 10.1; p = 0.003; d = 0.96), and response time for emotional recognition (F((1,47)) = 6.7; p = 0.013; d = 0.44). CONCLUSION: OSU treatment did not cause short-term cognitive side effects, further supporting the potential of OSU as a clinically feasible pharmacological treatment in AD patients. OSU treatment might improve future planning, verbal divergent thinking, and emotional recognition latency, which in turn may have a beneficial impact on alcohol use outcomes. Future studies are needed to confirm these preliminary findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00213-019-05345-6) contains supplementary material, which is available to authorized users.