BackgroundThe empathogen 3,4-methylenedioxymethamphetamine (MDMA) is the prototypical prosocial club drug inducing emotional openness to others. It has recently been shown that acutely applied 3,4-MDMA in fact enhances emotional empathy and prosocial behavior, while it simultaneously decreases cognitive empathy. However, the long-term effects of 3,4-MDMA use on socio-cognitive functions and social interactions have not been investigated yet. Therefore, we examined emotional and cognitive empathy, social decision-making, and oxytocin plasma levels in chronic 3,4-MDMA users.MethodsWe tested 38 regular but recently abstinent 3,4-MDMA users and 56 3,4-MDMA-naïve controls with the Movie for the Assessment of Social Cognition, the Multifaceted Empathy Test, and the Distribution Game and the Dictator Game. Drug use was objectively quantified by 6-month hair analyses. Furthermore, oxytocin plasma levels were determined in smaller subgroups (24 3,4-MDMA users, 9 controls).Results3,4-MDMA users showed superior cognitive empathy compared with controls in the Multifaceted Empathy Test (Cohen’s d=.39) and in the Movie for the Assessment of Social Cognition (d=.50), but they did not differ from controls in emotional empathy. Moreover, 3,4-MDMA users acted less self-serving in the Distribution Game. However, within 3,4-MDMA users, multiple regression analyses showed that higher 3,4-MDMA concentrations in hair were associated with lower cognitive empathy (βMDMA=-.34, t=-2.12, P<.05). Oxytocin plasma concentrations did not significantly differ between both groups.ConclusionsWe conclude that people with high cognitive empathy abilities and pronounced social motivations might be more prone to 3,4-MDMA consumption. In contrast, long-term 3,4-MDMA use might nevertheless have a detrimental effect on cognitive empathy capacity.