Comparative neuropsychopharmacology of methamphetamine (“Crystal Meth”) and MDMA (“Ecstasy”) on facets of cognitive control and impulsive behavior in social and non-social contexts: integrating behavior, psychophysiology, and neurochemistry

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The use of methamphetamine (METH, “Crystal Meth”) and 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) currently increases in Europe. Previous work has shown that both METH and MDMA users suffer from overlapping but also different deficits in a variety of impulse control functions that are related to the specific chronic effects of the drugs on monoamine, glutamate, and gamma-aminobutyric acid (GABA) systems. In particular, cognitive impairments impact the social functions of the users. The main goal of this project is to compare the chronic effects of METH and MDMA on the modulation of different facets of impulsive behavior by social and non-social contexts, as well as on the underlying functional brain mechanisms. These comparisons are achieved by employing a multi-method approach integrating behavioral and electrophysiological (EEG) data with neurochemical information derived from magnetic resonance spectroscopy (MRS). We investigate the effect of varying emotional contents (such as angriness and happiness) during conflict monitoring processes requiring inhibitory control mechanisms. In a second experimental paradigm we examine premature responding impulsivity (PRI) during contexts of reward acquisition and loss avoidance using computational modelling. We relate psychophysiological processes underlying modulations of different facets of impulsive behavior by social and non-social contexts to structural-neurobiochemical changes at the striatal GABA and GLU level in METH and MDMA users. This allows a comprehensive evaluation and comparison of mechanistic factors at a structure-specific neurochemical level with neurophysiology and behavior. The focus on the GABAergic and glutamatergic changes in the basal ganglia is important, given that compounds modulating these systems may be interesting candidates in the treatment of stimulant addiction. Thus, the project is crucial to discover new therapeutic approaches in order to i) improve impulse control deficits and related social problems in the daily life of the METH and MDMA users and ii) to better treat METH addiction for which no approved pharmacological treatment exists so far.