Bupropion pretreatment increased the maximum plasma concentration and overall exposure of both MDMA stereoisomers, while reducing the levels of its major metabolites by about 40%, in healthy volunteers. These changes in MDMA pharmacokinetics due to reduced CYP2D6 activity were similar to those seen in people with naturally lower CYP2D6 function (intermediate metabolizers). The alterations in stereoselectivity based on CYP2D6 activity likely have low clinical relevance. Bupropion and its metabolite levels were not affected by MDMA co-administration.
Chronic methamphetamine users show diminished cognitive and emotional empathy toward positive stimuli, elevated punitive social behavior regardless of provocation, and heightened self-reported trait anger compared to non-users. Chronic MDMA users differ from controls only by displaying increased punitive behavior when provoked. Higher hair concentrations of both drugs may be linked to reduced cognitive empathy, and greater lifetime MDMA use correlates with more punitive behavior among MDMA users. The dopaminergic mechanism of methamphetamine may underlie social-cognitive deficits.
Chronic users of methamphetamine and MDMA show similar deficits in conflict control and emotional processing, rather than substance-specific differences. In an emotional face-word Stroop task with anger and happy faces, both user groups exhibited smaller behavioral effects of cognitive-emotional conflict and selective impairments in processing anger, compared to amphetamine-naïve controls. These deficits were accompanied by stronger P3 event-related potential modulations, indicating altered stimulus-response mapping and decision-making. The findings suggest that chronic use of substituted amphetamines may affect noradrenergic systems, which could underlie the observed similarities. Understanding noradrenaline's role in these processes is an important direction for future research.