Using EEG in an oddball emotional‑faces task, the study demonstrates that MDMA—but not methamphetamine—selectively enhances the face‑sensitive N170 component for happy and angry versus neutral expressions, indicating boosted early visual processing of salient socio‑emotional stimuli. This drug‑specific effect suggests a neural mechanism for MDMA's prosocial and anxiolytic actions and supports its therapeutic investigation for social anxiety and related disorders.
The 3,4‐methylenedioxymethamphetamine (MDMA) has long been used non‐medically, and it is currently under investigation for its potential therapeutic benefits. Both uses may be related to its ability to enhance empathy, sociability, emotional processing and its anxiolytic effects. However, the neural mechanisms underlying these effects, and their specificity to MDMA compared to other stimulants, are not yet fully understood. Here, using electroencephalography (EEG), we investigated the effects of MDMA and a prototypic stimulant, methamphetamine (MA), on early visual processing of socio‐emotional stimuli in an oddball emotional faces paradigm. Specifically, we examined whether MDMA or MA enhance the processing of facial expressions, compared to placebo, during the early stages of visual perception. MDMA enhanced an event‐related component that is sensitive to detecting faces (N170), specifically for happy and angry expressions compared to neutral faces. MA did not affect this measure, and neither drug altered other components of the response to emotional faces. These findings provide novel insights into the neural mechanisms underlying the effects of MDMA on socio‐emotional processing and may have implications for the therapeutic use of MDMA in the treatment of social anxiety and other psychiatric disorders.
Haggarty and colleagues situate this study within evidence that acute 3,4-methylenedioxymethamphetamine (MDMA) increases sociability, empathy and social perception on self-report and behavioural measures, while reducing social anxiety and sensitivity to negative emotions. Previous work has proposed that MDMA's prosocial effects may involve serotonin and oxytocin systems, but the neural mechanisms mediating enhanced social processing are not fully characterised. Event-related potentials (ERPs) elicited by emotional faces—particularly the N170 (face structural encoding), P300 (attention allocation) and mismatch negativity (MMN; novelty detection)—provide a means to examine early visual and socio-emotional processing and how it is altered by psychoactive drugs. This study tested whether MDMA selectively enhances early visual processing of socio-emotional stimuli compared with a prototypic stimulant, methamphetamine (MA), and placebo. Using a double-blind, within-participant design, the investigators administered MDMA (100 mg), MA (20 mg) and placebo in separate sessions and recorded EEG during an emotional oddball faces task. The primary hypothesis was that MDMA, but not MA, would increase N170 and possibly P300 amplitudes for emotionally salient faces, indicating enhanced early processing of social cues. The work aims to clarify whether MDMA's neural effects on social processing differ from those of a standard stimulant and to inform considerations for therapeutic applications of MDMA-assisted interventions.
Papers cited by this study that are also in Blossom
Atila, C., Christ-Crain, M., Liechti, M. E. et al. · Lancet Diabetes Endocrinol (2023)
Bedi, G., Hyman, D., De Wit, H. · Biological Psychiatry (2010)
Holze, F., Vizeli, P., Müller, F. et al. · Neuropsychopharmacology (2019)
Bershad, A. K., Miller, M. A., Baggot, M. J. et al. · Journal of Psychopharmacology (2016)
The study employed a double-blind, within-participant design. Healthy adults (N = 25; 17 men, 8 women; mean age 27.4 years) who reported 4–40 prior MDMA experiences were recruited. Key inclusion criteria included fluency in English, BMI 18–26 and general good health; exclusion criteria included prescription medication use, cardiac disease or high blood pressure and previous negative experiences with MDMA or hallucinogens. Women not using oral contraceptives were tested during the follicular menstrual phase. Sessions were separated by at least 4 days (mean = 7.5 days). Participants completed three 4-hour drug sessions (09:00–13:00) in which they received, under double-blind conditions, capsules containing MDMA 100 mg (powdered MDMA), methamphetamine (MA) 20 mg (tablets), or placebo (dextrose). Urine and breath tests screened for recent drug or alcohol use, and pregnancy tests were performed for female participants. EEG electrodes were placed ~30 minutes after capsule ingestion and recording began ~60 minutes post-capsule; EEG measures for the reported task were obtained between 60 and 150 minutes after dosing. After EEG recordings, participants completed valence and arousal ratings for the faces they had seen. EEG was recorded with a 64-channel electro-geodesic net, sampled at 1024 Hz (down-sampled to 512 Hz offline), high-pass filtered at 1 Hz and low-pass filtered at 60 Hz. Independent component analysis was used to remove artefacts (blinks, eye movements, muscle, EKG). Data were segmented from −200 to 1000 ms relative to stimulus onset and baseline corrected; segments with remaining ±100 μV were rejected. A threshold of >80% good segments was required for inclusion; all participants met this threshold. The behavioural task was an emotional oddball paradigm with 300 stimuli (80% frequent cartoon faces, 20% infrequent human faces). Infrequent human faces were presented in separate blocks by emotion (happy, angry, neutral) to permit valence-specific analysis. Participants indicated whether a stimulus was a human or cartoon face via button press. Primary ERP outcomes were: N170 measured at PO8 (mean peak 150–200 ms), P300 at Pz (mean peak 300–400 ms) and MMN at Fz (240–350 ms). Analyses compared each drug to placebo separately using repeated-measures ANOVAs with factors for emotion (three levels) and drug condition. Self-report measures included the Drug Effects Questionnaire and visual analogue scales for friendliness/sociability; face valence/arousal ratings used a −4 to +4 Likert scale. Peak change from baseline and paired t-tests were used for subjective measures.
Demographics and blinding: The sample comprised 17 men and 8 women (mean age 27.4 years) with a mean of 7.1 prior MDMA uses. On the session-end questionnaire, 64% of participants correctly identified placebo, 20% correctly identified MA and 52% correctly identified MDMA, indicating partial success of blinding. Subjective effects: Both MDMA and MA increased ‘‘Feel Drug’’ ratings relative to placebo (MDMA: t(24) = 7.83, p < .001; MA: t(24) = −2.03, p = .05). MDMA increased ‘‘liking’’ compared with placebo (t(24) = −3.93, p = .001) while MA did not reach conventional significance for liking (t(24) = −2.00, p = .06). Both drugs increased ‘‘wanting more’’ (MDMA: t(24) = −3.32, p = .003; MA: t(24) = −2.38, p = .03). On VAS measures, MDMA increased feelings of friendliness (t(23) = −2.06, p = .05); MA increased both friendliness (t(23) = −2.15, p = .04) and sociability (t(24) = −2.14, p = .04). End-of-session liking means were higher for MDMA (mean = 78.0) and MA (mean = 71.2) than placebo (mean = 48.2). Face ratings and behavioural performance: Participants rated happy faces as more positive and angry faces as more negative than neutral faces, as expected. Neither MDMA nor MA altered these valence or arousal ratings according to the extracted text. ERP findings — N170: The principal neurophysiological finding was that MDMA significantly increased N170 peak amplitude at PO8 for emotional faces, specifically for happy and angry faces compared with neutral faces. Reported means were: for happy faces MDMA M = −2.27 μV versus placebo M = −1.04 μV; for angry faces MDMA M = −2.09 μV versus placebo M = −1.31 μV. The drug × emotion interaction for MDMA versus placebo was significant (F[2,86] = 4.49, p = .01, ηp2 = .10). There was also a main effect of emotion across MDMA and placebo (F[2,88] = 7.86, p = .001, ηp2 = .15). In contrast, MA did not affect N170 amplitude relative to placebo (drug × emotion interaction F[2,86] = 0.31, p > .05, ηp2 = .007), and in the MA versus placebo analysis emotion did not show a significant main effect (F[2,86] = 1.21, p > .05, ηp2 = .03). ERP findings — P300 and MMN: Neither MDMA nor MA produced significant changes in P300 amplitude relative to placebo; the P300 was smaller for cartoon than human faces but was not modulated by emotion or drug in the reported analyses. The MMN, measured at Fz, was greater for infrequent human faces than for frequent cartoon faces, consistent with novelty sensitivity, but neither drug altered MMN amplitude for emotional faces. Initial analyses indicated responses to frequent cartoon faces differed markedly from infrequent human faces across ERP measures; final reported ERP analyses therefore focused on human faces and compared each drug separately to placebo.
Haggarty and colleagues interpret their results as evidence that MDMA selectively enhances early visual processing of socio-emotional stimuli, as indexed by increased N170 amplitude for happy and angry faces. They propose that this potentiation of the N170 reflects augmented structural encoding of emotionally salient faces and may occur prior to effects on later cognitive processes. The absence of MDMA effects on P300 and MMN suggests the drug did not broadly alter attention allocation or novelty detection in this task, so the effect appears relatively specific to early face-sensitive visual processing. The authors relate the N170 finding to prior observations that oxytocin can enhance N170 responses to faces, noting that MDMA's prosocial effects have been linked to oxytocin and serotonergic systems; the parallel is presented as consistent with the idea that enhanced early face processing could support social approach or avoidance behaviours. They also contrast MDMA with MA, noting MA did not modulate N170 and therefore MDMA may differ from prototypic stimulants in its effects on social processing. Several limitations are acknowledged. The sample was homogeneous (healthy adults aged 18–35 with prior MDMA use) and modest in size, which may limit generalisability and sensitivity to subtle effects. Only single doses of MDMA (100 mg) and MA (20 mg) were tested, and the MA dose may not be potency-matched to MDMA across relevant transporter targets; dose–response studies would be needed. The inter-session washout of at least 4 days (mean 7.5 days) was shorter than the five half-lives often used in pharmaceutical trials and may not guarantee full neurochemical recovery, particularly for serotonergic systems. Task limitations are also noted: the emotional oddball paradigm used cartoon faces as frequent stimuli and segregated emotions by block, which may influence sensitivity to some effects; more ecologically valid or complex social tasks could reveal additional drug effects. In terms of implications, the investigators suggest that MDMA's enhancement of early neural responses to facial emotion cues could contribute to therapeutic mechanisms in MDMA-assisted psychotherapy by increasing attention to and processing of interpersonal emotional signals, potentially strengthening therapeutic alliance and emotional engagement. They call for further studies to clarify valence-specific effects, dose dependencies, longer inter-session intervals, and how these neural changes relate to behavioural and clinical outcomes.
specific behavioural and neural effects of MDMA are not fully understood. There is considerable evidence that acute doses of MDMA increase sociability, social perception and empathy. On self-report measures, the drug increases feelings of empathy, openness and social connectedness and decreases social anxiety and fear, effects that may enhance social interactions. On behavioural tasks, MDMA reduces sensitivity to negative emotions such as fear or anger, and reduces social anxiety in some populations. It also increases generosity and increases the pleasantness of social touch. These laboratory findings complement users' anecdotal reports that the drug produces prosocial and entactogenic effects. The neural and hormonal mechanisms by which MDMA acts are not fully understood. Its effects may be related to actions on serotonin or oxytocin systems, both of which are implicated in social behaviour, stress, and social bonding. The evidence that its effects are related to oxytocin are mixed, some show that behavioural responses to MDMA are correlated with increases in oxytocin, while others not. One recent studyshowed that participants with oxytocin deficiency showed greatly attenuated responses to MDMA, suggesting that adequate baseline oxytocin function may be essential for the drug's effects. One way to study the neural effects of MDMA on brain function is to study how the drug alters eventrelated potentials (ERPs) in response to emotional stimuli. Images of emotional faces in an oddball task elicit three distinctive ERP components: N170, P300 and mismatch negativity (MMN). The N170 component is a negative waveform that is thought to reflect the processing of facial features and the structural encoding of faces. The P300 component is a larger positive waveform that is thought to reflect attention allocation and cognitive processing. Finally, the MMN component is a negative waveform that occurs approximately 200-300 ms after stimulus onset and appears to respond to novel stimuli. The effects of a drug on these components in response to emotional stimuli may advance our understanding of how the drug alters responses to emotionally salient stimuli. Here we conducted a double-blind study examining effects of MDMA and MA, compared to placebo, on these EEG responses to emotional faces. We contrasted MDMA to a prototypic amphetamine, MA, which is thought to lack the strong prosocial effects of MDMA. Healthy young adults received MDMA (100 mg), MA (20 mg) or placebo during three sessions. We measured electrophysiological responses to emotional and neutral faces using an emotional oddball task. We hypothesized that MDMA, but not MA, would enhance the N170 and P300 ERP components associated with socioemotional processing specifically for more salient stimuli. The aim of this study was to determine how MDMA affects the brain's processing of social stimuli, including positive, negative and neutral faces. We also sought to determine whether the effect of MDMA differs from the effect of a prototypic stimulant, methamphetamine.
The study used a double-blind, within-participant design in which healthy adults received MDMA (100 mg), MA (20 mg) and placebo (PLC) on three separate sessions. At the expected time of peak drug effect participants engaged in an oddball task during which we recorded EEG responses to positive, negative and neutral faces. ERP components related to different aspects of emotional and cognitive processing were recorded. Participants also completed self-report measures of the drugs' effects. The study was approved by the University of Chicago internal review board and all procedures were in line with the declaration of Helsinki.
Healthy men and women (N = 25) aged 18-35 were recruited from the university and surrounding neighbourhoods. Eligibility was determined first by online screening and then by clinical interview and physical examination. Inclusion criteria consisted of a minimum high school education, fluency in English, BMI 18-26, and good health. Exclusion criteria included use of prescription medications, history of cardiac disease or high blood pressure and previous negative experience with MDMA or hallucinogenic substances. Participants had to report between 4 and 40 previous experiences of MDMA to qualify for the study. Women who were not on oral contraceptives were tested only during the follicular phase (1-12 days from menstruation;.
Participants first attended an orientation to understand the procedures, provide informed consent and practice the tasks from the experimental sessions. They were instructed to abstain from drugs and alcohol for 24 h before their sessions. They were told they would receive a sedative (e.g., Valium), stimulant (e.g., MDMA or amphetamine) or placebo drug in each session. The study was approved by the local institutional review board. The three, 4-h drug sessions were conducted from 9 AM to 1 PM, separated by at least 4 days (M = 7.5 days). Upon arrival at the laboratory, participants completed a breathalyser and urine sample to test for recent drug use (CLIA waived Instant Drug Test Cup, San Diego, CA; amphetamine, cocaine, oxycodone, THC, PCP, MDMA, opiates, benzodiazepines, barbiturates, methadone, methamphetamine and buprenorphine), alcohol use (Alcosensor III, Intoximeters, St. Louis, MO) and pregnancy (in females; Aimstrip, Craig Medical, Vista, CA). They completed pre-capsule questionnaires and cardiovascular measures, measures that were repeated 60, 90, 180 and 240 min after the capsule. They ingested capsules containing dextrose (placebo), MA (20 mg) or MDMA (100 mg) under double-blind conditions. Thirty minutes after taking the capsule participants' EEG electrodes were placed, and recording began about 60 min after the capsule. Resting state EEG was determined first, and this was followed by three tasks completed in randomized order. Here we report data on an emotional oddball task assessing responses to happy, angry, and neutral faces. The EEG measures were obtained from 60 to 150 min post-capsule. After the EEG electrodes were removed, participants rated the arousal and valence of the faces they viewed during the EEG task. Participants left the laboratory after the final measure, 240 min post capsule.
MDMA in powdered form (100 mg; Organix Inc, MA) was placed in opaque size 00 capsules with lactose filler. MA tablets (5 mg, total dose 20 mg; Desoxyn, Lundbeck) were placed in an opaque size 00 capsule with dextrose filler, and placebo capsules contained only dextrose.
1. The Drug Effects Questionnaire (DEQ;The DEQ consists of 100-point visual analog
A 64-channel electro-geodesic net was used (Magstim, EGI). Electrodes were soaked in a saline solution and then placed on the head using measurements from nasion to inion and mastoid to mastoid. EEG data was acquired continuously, amplified and digitized using Netstation software, and sampled online at 1024 Hz with impedances below 50kΩ. Offline EEG recordings were analysed using EEGLabwas first down-sampled to 512 Hz then high pass filtered (1 Hz), and low pass filtered (60 Hz, À12 dB/ octave) to remove extraneous high and low-frequency noise. Data were visually inspected for movement and electronic artefact, that is, periods of data with excessive noise affecting all electrodes. PICARD Independent Components Analysiswere performed to correct for EEG artefacts including blinks, horizontal and vertical eye movements, muscle movement and EKG signal only. Data were segmented from À200 to 1000 ms and baseline corrected following stimulus presentation for each of the stimulus types. Before the values were averaged, artefact detection was used to classify any segment of data with ±100 μV remaining and segment breaks from earlier cleaning. Further, a threshold of >80% was selected for inclusion in averaging for ERPs, all participants met this threshold.
To assess the neural responses to emotional stimuli, participants completed an emotional oddball task. The task consisted of 300 stimulus presentations, of which 80% were cartoon faces, and 20% were human faces. The stimuli were presented in three blocks of 100 stimuli consisting of the frequent cartoon image interspersed with infrequent angry, happy, or neutral faces. Emotional faces were not mixed within blocks to allow for individual consideration of each valence. Subjects were instructed to respond on the left key on a button box when they saw a human face and, on the right when they saw a cartoon face. ERPs were recorded during each stimulus presentation. 2.6 | Behavioural measure
Following the EEG session participants completed a ratings task in which they rated the 6 faces presented in the oddball task for valence and arousal. Valence and arousal were rated on a Likert scale from À4 (Very Negative/Not at all) to +4 (Very Positive/Extremely). Participants were told to indicate how positive or negative they perceived each face (valence) and how strongly they felt that emotion (arousal) (Figure).
1. Subjective and behavioural measures were assessed with analysis of variance using peak change score from baseline, using individual paired samples T-tests to measure the differences between Placebo versus MA and Placebo versus MDMA. Peak drug effects were calculated by subtracting the baseline values from the highest or lowest value during the session. 2. Faces Ratings Task (supplementary results). Participants rated the valence and arousal of each of the six faces seen in the emotional oddball task (male and female; angry, happy, neutral). These ratings were analysed using two 3  2 (emotion  MDMA [vs. PLC]; emotion  MA [vs. PLC]) ANOVAs. 3. Emotional Faces Oddball Task. The N170 was measured at electrode PO8, extracting the mean peak from 150 to 200 ms post stimulus onset. The P300 was measured at electrode parietal (Pz) extracting the mean peak between 300 and 400 ms. The MMN was measured using electrodes Fz between 240 and 350 ms. While electrodes of interest were selected based on these previous studies, specific time windows were chosen through visual inspection of grand average ERPs. For each of these peaks of interest, two 3 (emotion)  2 (Drug condition; Drug vs. PLC) repeated measures ANOVAs were conducted. We also examined ERP responses to the frequent cartoon faces for MMN to compare frequent versus infrequent stimuli. Initial analyses (supplementary materials) revealed that responses to the (infrequent) human faces differed from markedly from responses to the (frequent) cartoon face on all three ERP measures. The final analyses were conducted only with the human faces, comparing MDMA and MA versus PLC separately. 3 | RESULTS
Participants were 17 men and eight women, mean age of 27.4 years, most of whom had completed partial college (Table). Participants had previously taken MDMA a mean of 7.1 times. None of the subjects were cigarette smokers. Sixty-four percent of participants correctly identified Placebo, 20% MA and 52% MDMA, showing the effectiveness of the blinding (Table).
Both MDMA and MA increased ratings of Feel Drug compared to PLC (MDMA, t(24) = 7.83, p < .001; MA, t (24) = À2.03, p = .05). MDMA increased ratings of drug liking relative to PLC (t(24) = À3.93, p = .001) but MA did not differ from PLC (t(24) = À2.00, p = .06). Both MDMA and MA increased wanting more drug ratings compared to PLC (MDMA, t(24) = À3.32, p = .003; MA, t(24) = À2.38, p = .03). For VAS ratings, MDMA significantly increased feelings of friendliness compared to PLC (t[23] = À2.06, p = .05), as did MA (t[23] = À2.15, p = .04). In contrast, MA but not MDMA increased feelings of sociability (t(24) = À2.14, p = 04) (Figure).
On the end of session questionnaire, 64% of participants correctly identified PLC, 20% of participants correctly identified MA as a stimulant, and 52% correctly identified MDMA (full breakdown in supplementary results). Subjects reported liking MDMA (mean = 78.0) and MA (mean = 71.2) more than PLC (mean = 48.2).
N170-Face processing (Figure). MDMA significantly increased N170 peak amplitude compared to PLC specifically for happy (MDMA/PLC; M = À2.27 μV/ M = À1.04 μV) and angry (MDMA/PLC; M = À2.09 μV/ M = À1.31 μV) faces (significant drug  emotion interaction, F[2,86] = 4.49, p = .01, η p 2 = .1). Regardless of whether participants received MDMA or PLC, the N170 amplitude was also greater with happy and angry faces compared to neutral faces (main effect of emotion F [2,88] = 7.86, p = .001, η p 2 = .15). MA did not affect the N170 peak amplitude, compared to PLC (no significant interaction between drug and emotion, F[2,86] = .31, p > .05, η p 2 = .007). In this MA versus PLC analysis, emotion did not affect peak N170 amplitude here (no main effect of emotion, F[2,86] = 1.21, p > .05, η p 2 = .03). P300-Emotion processing (Figure). MDMA did not affect the P300 peak amplitude compared to PLC (no significant interaction between drug and emotion [F {2,86} = 1.).
The current study investigated the effects of two drugs, MDMA and MA, compared to placebo, on evoked potential responses to emotional stimuli in healthy adults. The two drugs produced their expected subjective effects. MDMA increased the N170 peak amplitude for happy and angry faces compared to neutral faces, but MA did not have this effect. The N170 is thought to reflect processing of facial features and is sensitive especially to emotional faces. Neither drug significantly altered P300 or MMN evoked potentials which are thought to reflect attention allocation and cognitive processing (P300) and responses to novelty (MMN). Both MDMA and MA had expected effects on subjective and behavioural measures. Both MDMA and MA increased ratings of feeling and liking the drug effect and wanting more of the drug. Both drugs also increased feelings of friendliness whereas only MA increased feelings of sociability. The lack of effect of MDMA on sociability was surprising considering some previous reports, and because MDMA is often described as a prosocial drug. It is known that social context can influence responses to MDMA, so it is possible that the solitary laboratory environment in the present study prevented the drug from producing feelings of sociability. As expected, participants rated happy faces more positively than neutral faces, and angry faces more negatively than neutral faces. However, neither MDMA nor MA altered these ratings. The main finding in this study was that MDMA, but not MA, enhanced the N170 amplitude in response to salient emotional faces. The drug increased N170 signals with happy and angry, but not neutral, faces. To our knowledge, the effects of MDMA and MA on N170 ERPs have not previously been examined. The N170 is thought to represent early structural encoding of face stimuli, especially faces expressing emotions. Emotional states can enhance the peak of this ERP. Interestingly, the prosocial hormone oxytocin reportedly increases N170 responses to faces, especially sad faces. The finding that the pro-social drug MDMA, like oxytocin, increased N170 responses to emotional faces is consistent with the idea that the N170 signals early social approach/ avoidance behaviours. This effect on N170 suggests that MDMA affects early visual processing of socially salient stimuli, before it produces other cognitive or emotional processes. MDMA has also been shown to increase the recall of positive and emotional memories but to not affect neutral ones, which is consistent with the idea that MDMA indeed enhances emotional processing. MA, which has less pronounced effects on social processes, did not affect the N170. It is important to consider also that there is evidence to suggest that long term MDMA use may impact social functioning differently. For example, Wunderli et al. () reported that long term MDMA users showed enhanced cognitive empathy but not emotional empathy. Comparativelyshowed that both cognitive and emotional empathy were enhanced in the MDMA users. Contrary to our expectations, neither MA nor MDMA affected the P300 peak amplitude. The P300 is thought to reflect attention allocation and cognitive processing and thus might be expected to be greater with more salient stimuli (emotional faces), and enhanced by drugs that increase attention. In the present study, the P300 was not affected by either emotions or either of the two drugs, although the P300 was smaller with cartoon faces compared to human faces. Although the cartoon faces were much more frequent than the human faces, it may also be that the P300 is sensitive to faces but not emotions. F I G U R E 1 Mean and standard error of the mean (SEM) for ratings of feel drug, liking, wanting more, visual analog scales (VAS) ratings of friendly and sociable for placebo (PLC) (green), methamphetamine (MA) (blue) and 3,4-methylenedioxymethamphetamine (MDMA) (red) sessions. MDMA significantly increased ratings for feeling the drug, liking drug effects, wanting more of the drug, and how friendly participants felt, compared to placebo, whereas MA significantly increased ratings of feeling the drug, wanting more drug, feeling friendly and sociable. The P300 is thought to reflect cognitive processing related to attention orientation. The lack of effect of either MDMA or MA on P300 is somewhat surprising, considering that both drugs are considered stimulants, which are thought to improve attention. Moreover, MDMA has been shown to increase visual attention to happy faces compared to other emotions, but this effect was not detected here with related EEG measures. Thus, the effects of MDMA and MA attention likely vary, depending on the measures that are used to assess attention, as well as the doses and participants studied. The MMN ERP was not affected by either MDMA or MA. Because the MMN is thought to signal a response to novel stimuli, this suggests that neither drug increased neural response to novelty. Regardless of the drug, the MMN ERP was greater with infrequent human faces than with frequent cartoon faces, supporting the idea that the MMN is an indicator of novelty. However, neither drug appeared to affect the neural indicator of novelty of the emotional faces. Although there is indirect evidence that stimulants increase the salience of stimuli, few other studies have examined the effects of stimulants specifically on MMN amplitude. In the present study, neither MDMA nor MA altered the brain's response to novelty in the context of emotional stimuli, even though MDMA altered stimulus salience as measured by the N170. Few studies have been conducted on the effects of other drugs on MNN. In one of few such studies, single doses of the selective serotonin uptake inhibitor escitalopram significantly increased MMN, without affecting P300 amplitude. Whether these ERP-related differences are related to the drugs' behavioural effects remains to be determined. Further research is needed to determine whether, or how, stimulant drugs affect this neural indicator of novelty. The study had several limitations. The sample was homogeneous, limited to healthy men and women aged 18-35, who had previously used MDMA. Thus, the results may not be generalizable to a more heterogeneous population including those with greater or lesser drug use histories. While the sample size was within the typical size for studies involving EEG recordings, more subtle effects would likely be detected with a larger sample. The study used only one dose of MDMA and MA, making it difficult to compare across drugs. That is, higher or lower doses of either drug may produce different effects, and future studies with dose responses are critical. MA is seven times more potent than MDMA at inhibiting noradrenaline transporters; therefore, it is important to consider that a higher dose of MA would be required to appropriately compare these drugs together; for this reason, the drugs were compared separately compared to PLC. In future studies, it would be beneficial to use more than one dose or match doses for their potency on one variable of interest. Another limitation is the 4-day washout period between sessions. Although this interval resulted in undetectable levels of MDMA on urine drug tests, it is shorter than the five half-lives typically used in pharmaceutical trials. Moreover, it is not clear how long an interval is needed for serotonin levels to return to normal after acute administration of the drug. Therefore, in future studies, it will be important to extend the inter-session interval. Finally, the study was limited by the task that was used, and it is possible that the emotional faces oddball task is not optimal for detecting the effects of these drugs. In future studies, more complex studies of social behaviour and motivation may parse the effects that MDMA is having on these processes. The present findings have implications for MDMAassisted therapy. The increased neural response to the sensory component of viewing faces could contribute to the therapeutic alliance between patients and their therapists. By increasing attention to facial emotional cues, the drug may increase interpersonal connection in the therapeutic environment. MDMA may also facilitate the identification and processing of emotions, allowing patients to build trust, and engage more deeply with their emotional experiences. Further studies of this kind are needed to understand the brain mechanisms underlying the behavioural effects of MDMA and other pro-social drugs. The main finding in this study was that MDMA, but not MA, increased the N170 peak amplitude for angry and human faces, compared to neutral faces. This finding is consistent with evidence that the N170 is selective for faces and sensitive to emotion. The effect of MDMA on N170 is consistent with both the known function of this ERP, with evidence that MDMA affects responses to social stimuli. An interesting and important future direction is to clarify whether MDMA equally affects both positive and negative emotional stimuli, as the present data suggest. This would have implications for its use in therapeutic settings. The finding that MA did not have similar effects suggests MDMA differs from other stimulants in the processing of social stimuli, although this conclusion must await testing with a full range of doses.
Create a free account to open full-text PDFs.
Carlyle, M., Stevens, T., Fawaz, L. et al. · Journal of Psychopharmacology (2019)
Danforth, A. L., Grob, C. S., Struble, C. et al. · Psychopharmacology (2018)
Doss, M. K., Weafer, J. J., Gallo, D. A. et al. · Neuropsychopharmacology (2017)
Dumont, G., Sweep, F., van der Steen, R. et al. · Social Neuroscience (2009)
´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., Delton, A. W., de Wit, H. et al. · Journal of Psychopharmacology (2015)
Kirkpatrick, M. G., Lee, R., Wardle, M. C. et al. · Neuropsychopharmacology (2014)
Kuypers, K. P. C., De La Torre, &. R., Farre, &. M. et al. · Psychopharmacology (2017)
Mitchell, J., Bogenschutz, M. P., Lilienstein, A. et al. · Nature Medicine (2021)
Nardou, R., Lewis, E. M., Rothhaas, R. et al. · Nature (2019)
Vizeli, P., Liechti, M. E. · Journal of Psychopharmacology (2017)
Wardle, M. C., De Wit, H. · Psychopharmacology (2014)
Papers in Blossom that reference this study
Mayo, L. M., Haggarty, C. J., Petrie, S. R. et al. · Psychopharmacology (2025)