Conflict monitoring and emotional processing in 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine users - A comparative neurophysiological study.

In stimulant use and addiction, conflict control processes are crucial for regulating substance use and sustaining abstinence, which can be particularly challenging in social-affective situations. Users of methamphetamine (METH, "Ice") and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") both experience impulse control deficits, but display different social-affective and addictive profiles. We thus aimed to compare the effects of chronic use of the substituted amphetamines METH and MDMA on conflict control processes in different social-affective contexts (i.e., anger and happiness) and investigate their underlying neurophysiological mechanisms. For this purpose, chronic but recently abstinent users of METH (n = 38) and MDMA (n = 42), as well as amphetamine-naïve healthy controls (n = 83) performed an emotional face-word Stroop paradigm, while event-related potentials (ERPs) were recorded. Instead of substance-specific differences, both MDMA and METH users showed smaller behavioral effects of cognitive-emotional conflict processing (independently of emotional valence) and selective deficits in emotional processing of anger content. Both effects were underpinned by stronger P3 ERP modulations suggesting that users of substituted amphetamines employ altered stimulus-response mapping and decision-making. Given that these processes are modulated by noradrenaline and that both MDMA and METH use may be associated with noradrenergic dysfunctions, the noradrenaline system may underlie the observed substance-related similarities. Better understanding the functional relevance of this currently still under-researched neurotransmitter and its functional changes in chronic users of substituted amphetamines is thus an important avenue for future research.

The functional connectome of 3,4-methyldioxymethamphetamine-related declarative memory impairments.

The chronic intake of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a data-driven multi-voxel pattern analysis (MVPA) approach on participants' resting-state functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to well-matched controls with moderate-to-strong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seed-based connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seed-based connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMA-related memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing.

Striatal Iron Deposition in Recreational MDMA (Ecstasy) Users.

BACKGROUND: The common club drug MDMA (also known as ecstasy) enhances mood, sensory perception, energy, sociability, and euphoria. While MDMA has been shown to produce neurotoxicity in animal models, research on its potential neurotoxic effects in humans is inconclusive and has focused primarily on the serotonin system. METHODS: We investigated 34 regular, largely pure MDMA users for signs of premature neurodegenerative processes in the form of increased iron load in comparison to a group of 36 age-, sex-, and education-matched MDMA-naïve control subjects. We used quantitative susceptibility mapping, a novel tool able to detect even small tissue (nonheme) iron accumulations. Cortical and relevant subcortical gray matter structures were grouped into 8 regions of interest and analyzed. RESULTS: Significantly increased iron deposition in the striatum was evident in the MDMA user group. The effect survived correction for multiple comparisons and remained after controlling for relevant confounding factors, including age, smoking, and stimulant co-use. Although no significant linear relationship between measurements of the amounts of MDMA intake (hair analysis and self-reports) and quantitative susceptibility mapping values was observed, increased striatal iron deposition might nevertheless point to MDMA-induced neurotoxic processes. Additional factors (hyperthermia and simultaneous co-use of other substances) that possibly amplify neurotoxic effects of MDMA during the state of acute intoxication are discussed. CONCLUSIONS: The demonstrated increased striatal iron accumulation may indicate that regular MDMA users have an increased risk potential for neurodegenerative diseases with progressing age.