The ongoing bioethical debate on pharmacological cognitive enhancement (PCE) in healthy individuals is often legitimated by the assumption that PCE will widely spread and become desirable for the general public in the near future. This assumption was questioned as PCE is not equally save and effective in everyone. Additionally, it was supposed that the willingness to use PCE is strongly personality-dependent likely preventing a broad PCE epidemic. Thus, we investigated whether the cognitive performance and personality of healthy individuals with regular nonmedical methylphenidate (MPH) use for PCE differ from stimulant-naïve controls. Twenty-five healthy individuals using MPH for PCE were compared with 39 age-, sex-, and education-matched healthy controls regarding cognitive performance and personality assessed by a comprehensive neuropsychological test battery including social cognition, prosocial behavior, decision-making, impulsivity, and personality questionnaires. Substance use was assessed through self-report in an interview and quantitative hair and urine analyses. Recently abstinent PCE users showed no cognitive impairment but superior strategic thinking and decision-making. Furthermore, PCE users displayed higher levels of trait impulsivity, novelty seeking, and Machiavellianism combined with lower levels of social reward dependence and cognitive empathy. Finally, PCE users reported a smaller social network and exhibited less prosocial behavior in social interaction tasks. In conclusion, the assumption that PCE use will soon become epidemic is not supported by the present findings as PCE users showed a highly specific personality profile that shares a number of features with illegal stimulant users. Lastly, regular MPH use for PCE is not necessarily associated with cognitive deficits.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an important modulator of cognitive and social functioning in cocaine addiction but it is unclear whether ADHD symptoms and cocaine use display mutually aggravating interaction effects on cognition, social functioning, and depressive symptoms. Therefore, we investigated the interaction of cocaine use and adult ADHD on social and non-social cognition and depressive symptoms. METHODS: Twenty-four cocaine users with (CU+ADHD) and 30 without ADHD (CU-ADHD), 29 cocaine-naïve ADHD patients, and 40 cocainenaïve healthy controls underwent comprehensive neuropsychological testing including assessment of social cognition (cognitive/emotional empathy and Theory-of-Mind). Additionally, depressive symptoms were measured with the Beck Depression Inventory. RESULTS: The effect size of global cognitive impairment was largest in CU+ADHD (d=1.22 vs. controls) followed by CU-ADHD (d=0.74), and cocaine-naïve ADHD patients (d=0.33). A similar pattern appeared regarding depressive symptoms (CU+ADHD: d=1.47; CU-ADHD: d=0.49, ADHD: d=0.34). In the measures of Theory-of-Mind (CU+ADHD: d=0.76; CU-ADHD: d=0.06, ADHD: d=0.01) and cognitive empathy (CU+ADHD: d=0.80; CU-ADHD: d=0.39, ADHD: d=-0.11) only CU+ADHD showed moderate to large impairments. Moreover, two-way analyses of covariance revealed a significant interaction effect of the factors ADHD and cocaine use on depressive symptoms (p<0.05) and Theory-of-Mind (p<0.05) but not on global cognitive performance (p=0.64). CONCLUSIONS: When occurring together, cognitive impairments associated with both ADHD and cocaine use are largely additive, whereas both factors seem to mutually potentiate one another with respect to mood and mental perspective-taking disturbances. Given the high comorbidity between ADHD and cocaine use, longitudinal studies are needed to investigate the origin of these potentiated impairments. ABSTRACTBackground: Attention-deficit/hyperactivity disorder (ADHD) is an important modulator of cognitive and social functioning in cocaine addiction but it is unclear whether ADHD symptoms and cocaine use display mutually aggravating interaction effects on cognition, social functioning and depressive symptoms. Therefore, we investigated the interaction of cocaine use and adult ADHD on social and non-social cognition and depressive symptoms. Conclusions: When occurring together, cognitive impairments associated with both ADHD and cocaine use are largely additive, whereas both factors seem to mutually potentiate one another with respect to mood and mental perspective-taking disturbances. Given the high comorbidity between ADHD and cocaine use, longitudinal studies are needed to investigate the origin of these potentiated impairments. Methods

Abbreviated running title:Discrete memory impairments in pure users of MDMA Original Article Submitted:Number of words in the abstract: 241/250 Number of words in the main text: 4493/5000 Number of Tables: 3 Number of Figures: AbstractChronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulantnaïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (dprimary=.90, dpolydrug=1.21), followed by working memory (dprimary=.52, dpolydrug=.96), executive functions (dprimary=.46, dpolydrug=.86), and attention (dprimary=.23, dpolydrug=.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use.