This comparative study (n=165) evaluated social cognitive functions and behaviors in chronic METH users, chronic MDMA users, and stimulant-naïve controls. METH users exhibited diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behavior regardless of provocation, and heightened trait anger. MDMA users showed a distinct rise in punitive behavior when provoked, with correlations suggesting associations between substance use patterns and social-cognitive deficits.
Methamphetamine (METH, “Crystal Meth”) and 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) share structural-chemical similarities but have distinct psychotropic profiles due to specific neurochemical actions. Previous research has suggested that their impact on social cognitive functions and social behaviour may differ significantly, however, direct comparisons of METH and MDMA users regarding social cognition and interaction are lacking. Performances in cognitive and emotional empathy (Multifaceted Empathy Test) and emotion sensitivity (Face Morphing Task), as well as aggressive social behaviour (Competitive Reaction Time Task) were assessed in samples of n = 40 chronic METH users, n = 39 chronic MDMA users and n = 86 stimulant-naïve controls (total N = 165). Self-reports and hair samples were used to obtain subjective and objective estimates of substance use patterns. METH users displayed diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behaviour regardless of provocation, and self-reported heightened trait anger relative to controls. MDMA users diverged from the control group only by exhibiting a distinct rise in punitive behaviour when faced with provocation. Correlation analyses indicated that both higher hair concentrations of MDMA and METH may be associated with reduced cognitive empathy. Moreover, greater lifetime MDMA use correlated with increased punitive behaviour among MDMA users. Our findings confirm elevated aggression and empathy deficits in chronic METH users, while chronic MDMA users only displayed more impulsive aggression. Dose-response correlations indicate that some of these deficits might be a consequence of use. Specifically, the dopaminergic mechanism of METH might be responsible for social-cognitive deficits.
Papers cited by this study that are also in Blossom
Bedi, G., Hyman, D., De Wit, H. · Biological Psychiatry (2010)
Bershad, A. K., Mayo, L. M., Van Hedger, K. et al. · Neuropsychopharmacology (2019)
Bershad, A. K., Miller, M. A., Baggot, M. J. et al. · Journal of Psychopharmacology (2016)
Carlyle, M., Stevens, T., Fawaz, L. et al. · Journal of Psychopharmacology (2019)
Methamphetamine (METH) and 3,4-methylenedioxy-methamphetamine (MDMA) are chemically related substituted amphetamines whose patterns of use and neurochemical actions differ markedly. Previous research has documented shared cognitive alterations among regular users of both substances, such as impaired impulse control and memory, but has also noted divergent effects on social cognition: chronic METH use has been linked to disturbances in emotion processing and increased hostility, whereas acute MDMA is reliably pro-social and some studies of recreational MDMA users have reported enhanced cognitive empathy. Much of the prior work, however, relied on self-report measures of substance use and has not directly compared chronic METH and chronic MDMA users within the same study. Zacher and colleagues set out to fill this gap by directly comparing chronic METH users, chronic MDMA users, and stimulant-naïve controls on objective and behavioural measures of social cognition and aggressive behaviour. The study combined laboratory tasks assessing cognitive and emotional empathy (Multifaceted Empathy Task, MET), sensitivity to changing facial emotions (Face Morphing Task, FMT), and punitive behaviour under provocation (Competitive Reaction Time Task, CRTT) with both subjective history and quantitative hair toxicology to examine dose-related and polysubstance-use effects. The investigators hypothesised that chronic METH users would show impaired cognitive and emotional empathy and elevated aggression, while regular MDMA users would show higher cognitive empathy, particularly for positive emotions, with little change in emotion sensitivity or aggression.
This was a cross-sectional case-control investigation conducted within a multicentre project (Dresden, Germany and Zurich, Switzerland). The analysed sample comprised 40 chronic METH users, 39 chronic MDMA users, and 86 pooled stimulant-naïve controls (controls were frequency-matched on age and sex across sites). Participants were aged 18–45 years. Substance-user inclusion required a minimum of 25 lifetime occasions of METH or MDMA use and recent use within the past 12 months, confirmed by hair analysis. Controls were stimulant-naïve by set criteria and excluded if they reported more than 15 lifetime illicit substance occasions (except cannabis). General exclusions included pregnancy, major neurological or severe psychiatric disorders likely to affect task performance, current psychotropic medication (not applicable to the METH group), and daily cannabis use (not applicable to the METH group). Participants abstained from illicit substances for at least 48 hours and alcohol for 24 hours before testing; abstinence was verified with urine screening. Procedurally, testing took place over two days. Day one included consent, clinical and substance-use assessments, and collection of hair and urine samples; day two included clinical questionnaires, urine screening and completion of an electroencephalogram in the larger protocol. Three behavioural tasks were administered in fixed order on day two: the Face Morphing Task (FMT), the Multifaceted Empathy Task (MET), and the Competitive Reaction Time Task (CRTT). The MET assessed cognitive empathy (emotion labelling) and emotional empathy (implicit arousal and explicit empathic concern) separately for positive and negative stimuli. The FMT measured sensitivity to graded morphs between angry and happy expressions and neutral perception. The CRTT operationalised punitive/aggressive behaviour by letting participants set noise intensity (1–8) as punishment across 25 trials, with analyses separating retaliatory from non-retaliatory responses. Substance use was characterised both subjectively via structured interviews and objectively via proximal hair samples (4 cm) analysed by LC-MS/MS; body hair was used when scalp hair was insufficient (n = 9). Additional measures included screening for DSM-IV/DSM-5 disorders, the CESD for depression, ADHD-SR, Barratt Impulsiveness Scale (BIS), STAXI-2 for state/trait anger, Need for Recovery Scale for fatigue, and a vocabulary test for premorbid verbal IQ. Statistical analyses were carried out in R 4.1.2. Group differences used chi-square tests and ANOVAs with FDR-corrected pairwise comparisons. Main outcome comparisons used multiple linear regressions with controls for sex, age and years of education; effect sizes reported as Cohen's f 2. Additional models incorporated BIS, CESD and SKB scores, and models controlling for recent and lifetime alcohol, cannabis and nicotine use were run. Hair concentrations and usage variables were log10-transformed with a constant of 1 for skewed distributions. Subgroup sensitivity analyses examined polystimulant MDMA users (n = 13 above forensic cut-offs) versus relatively pure MDMA users (n = 26), and MDMA users with any amphetamine (n = 21) or cocaine residuals (n = 25) were analysed separately. The authors stated that analysis code and data would be shared on request.
Sample characteristics showed group differences in sex distribution, years of education, verbal IQ, and questionnaire measures including ADHD-SR, CESD and BIS; METH users also had higher trait anger (STAXI). Hair toxicology confirmed methamphetamine as the primary recent substance in METH users. Although MDMA was the most reported substance among MDMA users, 54% and 62% of that group reported recreational amphetamine and cocaine use respectively, supported by hair residuals; pooling and sensitivity analyses addressed polystimulant use. Controls had no appreciable METH or MDMA hair residues. On the Multifaceted Empathy Task, regression models controlling for sex, age and education indicated that METH users performed worse than controls on both cognitive and emotional empathy for positive stimuli. No group contrasts reached significance for negative stimuli. MDMA users did not differ from controls on cognitive or emotional empathy. When impulsivity (BIS), depressive symptoms (CESD) and fatigue (SKB) were added as covariates, the contrasts between METH users and controls in empathy for positive stimuli lost statistical significance (adjusted p = .051 for cognitive empathy and p = .200 for emotional empathy). Performance in the Face Morphing Task showed no significant group differences for the angry, happy or neutral conditions in models controlling for demographics; adding BIS, CESD and SKB did not change this result. In the Competitive Reaction Time Task, METH users selected higher punishment levels than controls in non-retaliatory trials and also differed from controls in retaliatory trials. MDMA users did not differ from controls in baseline punishment levels, but paired t-tests showed all groups increased punishment from non-retaliatory to retaliatory trials (METH t = 3.318, p < .01; MDMA t = 5.274, p < .001; controls t = 4.560, p < .001). An ANOVA with Tukey HSD post-hoc tests indicated MDMA users exhibited a significantly larger increase in punishment from non-retaliatory to retaliatory trials compared with controls (mean difference = 0.549, adjusted p < .05). Adding BIS, CESD and SKB to the CRTT models attenuated some group contrasts (the MDMA vs METH difference in non-retaliatory punishment became adjusted p = .072). Doubts about the opponent's legitimacy were infrequent and did not alter results when controlled for. Sensitivity analyses that included recent or lifetime alcohol, cannabis and nicotine use altered some findings: several contrasts (including differences between MDMA and METH users and between METH users and controls in positive emotional empathy and non-retaliatory punishment) lost significance when other substance use was accounted for. Dose–response analyses yielded some uncorrected associations that did not survive FDR correction: in METH users higher hair methamphetamine concentration was associated with lower cognitive empathy for positive stimuli (f 2 = 0.213, β = -0.420, uncorrected p < .05). Among MDMA users, higher MDMA hair concentrations were associated with lower cognitive empathy for positive stimuli (f 2 = 0.138, β = -0.368, uncorrected p < .05) and with higher scores in the angry condition of the FMT (f 2 = 0.127, β = 0.358, uncorrected p < .05). Cumulative lifetime MDMA dose positively predicted retaliatory punishment in the CRTT (f 2 = 0.131, β = 0.375, uncorrected p < .05). METH craving predicted positive cognitive empathy in models controlling for positive urine (f 2 = 0.151, β = 0.348, uncorrected p < .05). Comparison of relatively pure versus polystimulant MDMA users did not show significant group differences. Among MDMA users, greater amphetamine residuals correlated with higher neutral FMT scores and higher cognitive empathy for negative stimuli (β = 0.538 and β = 0.422 respectively, uncorrected p < .05). The authors note some missing hair samples for METH users and emphasise that dose-related p-values did not survive FDR correction.
Zacher and colleagues interpret their findings as evidence that chronic METH and MDMA use are associated with distinct social-cognitive and social-behavioural profiles. Chronic METH users exhibited reduced cognitive and emotional empathy for positive stimuli and elevated punitive behaviour irrespective of provocation, along with higher self-reported trait anger. The investigators suggest these effects may relate to chronic METH-induced alterations in dopaminergic function, reward processing and attendant mood symptoms, which could selectively impair processing of positive emotions and thereby contribute to aggressive tendencies and social difficulties. In contrast, chronic MDMA users did not show the previously reported enhancement in cognitive empathy; instead, they displayed a larger behavioural increase in punishment in response to provocation compared with controls. The authors propose that this pattern reflects task-specific impulsivity and possibly cumulative serotonergic changes with heavier MDMA exposure. They also consider alternative explanations for the divergence from prior reports of enhanced empathy in MDMA users, including differences in dosage or a U-shaped dose–response relationship in which light use associates with higher empathy but heavier or longer-term use does not. The dose–response correlations observed in hair analyses—associating higher recent concentrations of either substance with reduced cognitive empathy and higher cumulative MDMA use with more retaliatory punishment—are presented cautiously because they did not survive correction for multiple comparisons. Several limitations acknowledged by the investigators temper causal interpretation. The cross-sectional design precludes firm inference about causality and the role of predisposition versus substance-induced change. Group differences were partly attenuated when controlling for impulsivity, depression, fatigue and other substance use (alcohol, cannabis, nicotine), indicating those factors may confound or mediate observed effects. Sex distribution was unbalanced across user groups, psychiatric comorbidity burden was higher in METH users, some hair samples were missing, recruitment occurred at two sites, and sample sizes—particularly within user subgroups—were moderate, which may have limited power to detect dose-dependent effects. The authors call for longitudinal studies that track social-cognitive change over time, consider chronicity and abstinence, and better disentangle predispositional factors from substance-induced alterations to inform tailored interventions and support for chronic stimulant users.
The present cross-sectional case-control study was part of a multicentre project, comparing three distinct groups: chronic METH users, chronic MDMA users, and stimulant-naïve controls. Participants from each group underwent a comprehensive battery of assessments focusing on cognitive, social-cognitive, and neural functioning. For the purposes of this report, we concentrate solely on the results from the socialcognitive and social-behavioural tasks. A total of N = 203 participants were initially recruited between June 2019 and July 2021 by means of online media and flyer advertisements placed in institutions involved in substance use information and prevention, addiction clinics, and in public places. The analysed sample included 40 chronic METH users and 45 age-and sex-matched stimulant-naïve controls from Dresden, Germany, as well as 39 chronic MDMA users and 42 age-, sex-, education-, verbal intelligence-, and nicotine use-matched stimulant-naïve controls from Zurich, Switzerland. Since controls from both locations did not significantly differ in relevant demographic and clinical variables, apart from sex distribution (see Supplementary Table), they were pooled into a single control group for all further analyses. All participants were aged 18 to 45 years. Substance users were eligible with a minimum of 25 lifetime occasions of MDMA or METH use and recent use within the last 12 months, respectively (confirmed by hair analysis). Either MDMA or METH had to be their primary illicit substance. General exclusion criteria included i) pregnancy or breastfeeding, ii) acute or previous severe somatic or neurological disorders, iii) severe DSM-IV Axis I psychiatric disorders affecting task performance such as autism and schizophrenia, iv) current intake of psychotropic medication (not applicable in the METH user group) and v) daily cannabis use (not applicable in the METH user group). Stimulant-naïve controls were excluded if they reported illicit substance use on more than 15 lifetime occasions (except cannabis) or intake of stimulants in the past 4 months (confirmed by hair analysis). All participants were asked to abstain from illicit substances for at least 48 h (verified through urine substance screening) and alcohol for 24 h before testing. Specific sample-related criteria and exclusions are detailed in Supplement Section 1. In accordance with the Declaration of Helsinki, all participants provided written informed consent and received compensation for their participation. The Ethics Committees of the Canton Zurich (BASEC-Nr. 2018-02125) and the TU Dresden (EK 69022018) approved the study protocol.
Statistical analyses were conducted in R version 4.1.2. Demographic and substance use data were analysed using Pearson's chi-square tests and analyses of variance (ANOVA), followed by False Discovery Rate (FDR)-corrected pairwise comparisons (α = 0.05). Group differences in social-cognitive and -behavioural parameters were assessed via multiple linear regressions. The control group served as the reference when comparing to both METH and MDMA users, while MDMA users were the reference for comparing METH and MDMA users. FDR-correction was applied retrospectively to control for multiple comparisons within tasks and group contrasts. For group contrasts, effect size Cohen's f 2 was reported (0.02 = small effect, 0.15 = medium effect, 0.35 = large effect). Sex, age, and years of education were included as control variables in the main regression models, considering their influence on empathic responses and social cognitive measures. In addition, separate models were constructed to incorporate impulsivity (BIS), depression (CESD), and current fatigue (SKB) scores, addressing their theorized impact on social cognition and decision-making, as supported by previous research in substance users. Due to their moderately strong correlation in the sample (r(162)=0.661, p < 0.001) and to facilitate a more focused consideration of the impulsive dimension, the BIS score was chosen over the ADHD score for its relevance to social cognition. Detailed coefficients of covariates can be found in Supplementary Section 3. Furthermore, to control for potential substance effects, social cognition parameters were regressed on self-reported measures of cannabis, alcohol, and nicotine use. Two models, one for the past six months (cumulative occasions) and another for lifetime substance use (cumulative dose), were run across all participants and for each subtask, integrating demographic and grouping variables. This approach aligns with previous investigations of MDMA users). An extra model, controlling for positive THC urine samples, was conducted due to several participants testing positive for THC. Lastly, to explore potential substance-specific effects on social cognition, multiple regression analyses were conducted independently for METH users and MDMA users only. In both cases, separate models estimating social cognition parameters through either substance use over the past 4 months (hair analyses) or cumulative lifetime substance dose were run, while retaining demographic control variables in the models. For METH users, additional models considered potential acute effects of METH use (positive urine samples) and METH craving. To investigate the impact of stimulant co-use among MDMA users on our results, a subgroup of n = 13 MDMA users exceeding the established forensic cut-off levels for amphetamine or cocaine in hair (200 and 500 pg/mg, respectively;) was compared to relatively pure MDMA users (n = 26). In an additional approach, two subgroups of MDMA users, one with any amphetamine residuals (n = 21) and another with any cocaine residuals (n = 25) in hair, underwent separate analyses to explore the potential effects of these substance residuals. Hair concentration and subjective substance use variables were log 10 -transformed with a constant of 1 to address right-skewed distributions, accounting for 0 values in the data. The analysis code and data will be shared upon request.
The present study compared the performance of chronic METH users, chronic MDMA users, and stimulant-naïve controls in different socialcognitive and -behavioural tasks. Hair toxicology and detailed psychiatric diagnostics were used to counteract the influence of underreported substance use and psychiatric comorbidities. Hair toxicology also confirmed that both user groups had been relatively pure users of their main substance in the recent months, at least aside from alcohol and nicotine. We demonstrated elevated punitive behavior in chronic METH users regardless of whether the situation called for retaliatory or nonretaliatory responses, while MDMA users exhibited a stronger increase in punishment when previously provoked. Additionally, METH users revealed lower cognitive and emotional empathy compared to controls. Neither METH nor MDMA users demonstrated significant deviations from controls in terms of emotion recognition sensitivity. Furthermore, we found substance-and dose-related alterations, in that both higher hair concentrations of MDMA and METH were associated with reduced cognitive empathy and greater cumulative lifetime MDMA use correlated with increased punitive behavior among MDMA users. Interestingly, METH users here showed inferior performance in recognizing emotions and experiencing feelings of others (cognitive and emotional empathy as assessed with the MET) primarily when positive stimuli were presented, whereas their performance was not affected when they were exposed to negative stimuli. These findings present a nuanced picture, deviating somewhat from prior research that primarily highlighted deficits in emotion recognition among individuals with METH dependence, often in the context of aversive emotions such as fear and anger. It is notable that earlier studies primarily employed tasks featuring isolated pictures lacking social context, whereas the MET presented participants with complex scenes, necessitating the integration of multiple layers of social information. While previous research has suggested a potential hostility bias among METH users, wherein non-threatening emotions are misclassified as hostile emotions, our study's design, which presented participants with only positive emotional answer choices in the positive condition, limits the applicability of this explanation to our findings. Alternatively, a more comprehensive perspective considers substance-related alterations in DA functions within the brain, coupled with disruptions in reward processing and shifts in emotional states, including depressive and anxiety symptoms commonly seen in METH users. These factors have independently been associated with disturbances in positive emotion regulation and cognitive empathyand may collectively contribute to the difficulties METH users face in perceiving and empathizing with positive emotions in others. Consistent with this perspective, our study found a correlation between higher METH concentration in hair and decreased cognitive empathy in response to positive stimuli, suggesting a link between long-term METH exposure and deficits in empathy, possibly mediated by DA alterations. Our findings diverge from past research indicating enhanced cognitive empathy in long-term MDMA users. Although our sample resembled that of thestudy, which associated increased empathy with the predominance of pure MDMA users, we did not observe a corresponding enhanced empathy. Our group had a similar proportion of pure and polystimulant MDMA users, with approximately a third of users exhibiting elevated amphetamine and cocaine concentrations. While bothandargued that improved cognitive empathy could be specifically associated with light rather than heavy MDMA consumption, our participants, who had considerably lower MDMA hair levels, did not display enhanced empathy. This challenges the notion that increased cognitive empathy is solely associated with pure or light MDMA use. Considering a U-shaped relationship between MDMA dosage and cognitive empathy might offer additional insights, suggesting an optimal threshold for light use where increased cognitive empathy remains valid, possibly even acting as a predisposing factor for MDMA use. However, beyond this threshold, lower or higher levels may not benefit (and may reduce) cognitive empathy. Considering a U-shaped pattern instead of a linear association, could help explain why the observed negative correlation between MDMA hair concentration and cognitive empathy failed to withstand correction for multiple comparisons, while directly aligning with findings reported byas well as results of increased self-reported emotional deficits with greater life-time exposure to MDMA. Regarding sensitivity to changes in the intensity of emotions measured with the FMT, neither METH nor MDMA users showed significant alterations. For METH users, this finding converges with previous research by, which observed impairments in recognizing anger but no evidence of altered sensitivity to increases in its intensity. Although acute administration of MDMA has been associated with heightened sensitivity to positive emotions and decreased sensitivity to negative emotions, the same may not hold true for chronic MDMA use. Our study is among the first to investigate emotional sensitivity alterations, rather than mere emotion recognition, in regular MDMA users, highlighting the need for further research in this area. Given our proposition that social-cognitive impairments can potentially contribute to behavior with social implications, such as aggression, we employed the CRTT to evaluate levels of aggressive behavior. Our results demonstrated an increase in aggressive actions in METH users during the CRTT. Notably, in contrast to past findings, this elevated aggression was observed regardless of whether a provocation from the fictional opponent occurred, which suggests that chronic METH use could potentially foster an inherent aggressive tendency that is not solely contingent on immediate provocation or explicit triggers. Importantly, our study also aligns with prior resultsby demonstrating that METH users not only displayed increased punitive behavior but also reported higher levels of trait anger. These results imply that METH users may exhibit a heightened tendency towards aggressive responses in general, rather than being limited to the specific experimental conditions. While MDMA users did not differ from controls in terms of baseline punishment levels, it is noteworthy that they exhibited a greater increase in punitive behavior from the non-retaliatory condition to the retaliatory condition, reflecting a pronounced response to experienced provocation. This observed response suggests a distinct behavioural pattern compared to both METH users and controls. In line with our finding that MDMA users in our study exhibited significant differences in subjective impulsivity ratings compared to controls, the observed behavioural pattern may suggest the presence of task-specific impulsivity. This interpretation is further supported by existing literature indicating heightened impulsivity among MDMA users. Interestingly, we also found that cumulative MDMA lifetime use positively predicted retaliatory punishment in the CRTT. Again, it is crucial to interpret this finding with caution, considering that it did not withstand FDR-correction. Despite this, it is plausible that the observed trend may be due to changes in 5-HT function associated with cumulative exposure to MDMA. Previous research has linked such alterations to heightened levels of impulsive aggression (da Cunha-Bang and Knudsen, 2021). Unexpectedly, there were no significant associations between selfreported lifetime METH use and social-cognitive parameters, despite the observed overall deficits. This may be influenced by limitations in self-report measures, including memory and social desirability biases and underreporting. The observed deficits may also be influenced by factors beyond mere lifetime METH dose, such as chronicity and severity of METH dependence, different stages of disorder, and duration of abstinence, as well as presence of other substance use disorders, that should be specifically considered in future research. The comparison between METH and MDMA users aimed to shed light on the multifaceted dynamics underlying substance use, social cognition, and the distinct trajectories associated with these chemically similar substances. Initially, our hypothesis suggested that chronic METH and MDMA use lead to distinct alterations in neurotransmitter systems, with DA and 5-HT playing pivotal roles, contributing to different changes in social functioning, a hypothesis confirmed by our results. For METH use, recognized for its impact on the DA system, we anticipated social-cognitive deficits translating into social-behavioural challenges, supported by studies in subclinical users of other amphetamine derivativesas well as in studies involving pharmacological manipulation of DA transmission in nonhuman primates (B.. These challenges might involve heightened aggression, fostering social isolation and reinforcing reliance on methamphetamine for self-medication or escape, creating a cycle of substance addiction (see also. In contrast, social-cognitive effects in MDMA users appear to follow a different trajectory due to distinct neuroadaptations in the 5-HT system, and the associated lower dependence potential, resulting in less pronounced or observable social-cognitive alterations compared to METH users. Our findings must be considered in the light of several limitations. First, our extended analyses revealed that impulsivity, depression, fatigue, and lifetime use of cannabis, nicotine, and alcohol could overshadow specific impacts of METH use, with initial differences in empathy compared to controls sometimes becoming non-significant after considering these factors. Future studies must meticulously consider various psychological and behavioural factors to isolate METH's unique influence on empathy. Secondly, it is crucial to acknowledge that pre-existing disparities in social and lifestyle preferences, intellectual abilities, comorbidities, as well as social stigma experienced in relation to the substance use may contribute to the observed social-cognitive alterations and play a relevant role in initiating or potentiating the addiction cycle. Despite our efforts to control for important demographic, clinical, and substance-related factors, as well as exploring dose-dependent effects, the cross-sectional nature of the study limits our ability to establish cause-effect relationships. The presence of only weak correlations between METH or MDMA use variables and social-cognitive measures further underscores this challenge. Longitudinal studies conducted with cocaine users have demonstrated that cognitive changes may be partly induced by substance use, as they covary with temporal changes in cocaine consumption. This suggests that some of the social-cognitive deficits observed in METH users may also be substance-induced. However, to gain a deeper understanding of the effects of predisposition and potential consequences, data from longitudinal studies specifically focusing on METH users are necessary. Furthermore, the sex distribution was unbalanced in the user groups, however, this was largely inevitable given that males are usually overrepresented in METH user samples in contrast to MDMA user samples. METH users also displayed a higher burden with current psychiatric symptoms, primarily in the ADHD, mood, anxiety, and psychosis spectrum. These psychiatric comorbidities, which are frequent among METH users, may contribute to the described complex downward spiral and may additionally affect social-cognitive functioning. Given the study focus, further investigation involving larger METH-dependent cohorts is essential to better understand the interaction between diverse comorbid psychiatric symptoms and social-cognitive deficits. Additionally, the MDMA sample mainly comprised individuals predominantly using MDMA, with rather low co-use of amphetamine or cocaine. While this focus allowed specific insights into the effects of MDMA, it may limit the generalizability to populations with different polysubstance use patterns. Furthermore, it is important to note that METH and MDMA users, as well as half of the control group were recruited each from two different locations. Lastly, the study's moderate sample size, particularly within user groups, could affect statistical power and the ability to detect robust dose-dependent effects. Taken together, the current comparative investigation sheds light on the distinct social-cognitive shifts tied to chemically similar substances. METH users exhibited heightened punitive behavior, reduced cognitive and emotional empathy, and reported increased trait anger, suggesting a disposition towards aggression and emotional dysregulation. In contrast, MDMA users did not show the previously reported heightened cognitive empathy but displayed a unique increase in punitive behavior under provocation. To comprehensively grasp chronic METH and MDMA effects on social cognition, future research should prioritize longitudinal studies. Examining the time-based evolution of socialcognitive deficits in both groups, considering factors like chronicity, abstinence, and substance use severity, will provide deeper insights into the complex interaction between substance use and social cognition. These insights will inform tailored interventions and support systems for chronic substance users, improving strategies to address their socialcognitive needs effectively.
Create a free account to open full-text PDFs.
Dolder, P. C., Müller, F., Schmid, Y. et al. · Psychopharmacology (2017)
´dric, C., Hysek, M., Schmid, Y. et al. · Social Cognitive and Affective Neuroscience (2013)
Kamilar-Britt, P., Bedi, G. · Neuroscience and Biobehavioral Reviews (2015)
Kirkpatrick, M. G., Lee, R., Wardle, M. C. et al. · Neuropsychopharmacology (2014)
Montgomery, C., Roberts, C. A. · Experimental Neurology (2021)
Opitz, A., Zimmermann, J., Cole, D. M. et al. · NeuroImage (2024)
Wardle, M. C., De Wit, H. · Psychopharmacology (2014)
Zimmermann, J., Zölch, N., Coray, R. et al. · International Journal of Neuropsychopharmacology (2023)