In controlled semi‑structured dyadic conversations, both MDMA (100 mg) and methamphetamine (20 mg) increased participants' feelings of connectedness relative to placebo. Both drugs elevated oxytocin, but only MDMA's oxytocin increase correlated with subjective closeness, indicating similar behavioural effects may arise from different neuroendocrine mechanisms and demonstrating a sensitive method for measuring pro‑social drug effects in person.
Papers cited by this study that are also in Blossom
Bershad, A. K., Miller, M. A., Baggot, M. J. et al. · Journal of Psychopharmacology (2016)
MDMA is a stimulant-like drug with distinctive empathogenic effects. Its pro-social effects, such as feelings of connectedness, may contribute to both its popularity as a recreational drug and its apparent value as an adjunct to psychotherapy. However, little is known about the behavioral processes by which MDMA affects social interactions. This investigation examined the effects of MDMA (100 mg versus placebo; N = 18) on feelings of connectedness with an unfamiliar partner during a semi-structured casual conversation. A separate study examined the effects of a prototypic stimulant methamphetamine (MA; 20 mg versus placebo; N = 19) to determine the pharmacological specificity of effects. Oxytocin levels were obtained in both studies. Compared to placebo, both MDMA and MA increased feelings of connection with the conversation partners. Both MDMA and MA increased oxytocin levels, but oxytocin levels were correlated with feeling closer to the partner only after MDMA. These findings demonstrate an important new dimension of the pro-social effects of MDMA, its ability to increase feelings of connectedness during casual conversations between two individuals. Surprisingly, MA had a similar effect. The findings extend our knowledge of the social effects of these drugs, and illustrate a sensitive method for assessing pro-social effects during in-person dyadic encounters.
Molla and colleagues frame MDMA as a stimulant-like compound with pronounced empathogenic and pro-social effects that may underlie both its recreational popularity and its emerging therapeutic utility, particularly as an adjunct in psychotherapy for post-traumatic stress disorder. The introduction notes that while animal and some human laboratory work have shown MDMA increases social approach, sociability and socioemotional processing, few controlled studies have examined how MDMA affects actual in-person social interactions, whether such effects are pharmacologically specific, or which physiological mechanisms (for example, oxytocin release) might mediate them. This paper reports two parallel within-subject, double-blind studies designed to address that gap. Study 1 tested the effects of MDMA (100 mg versus placebo; initial N = 18) and Study 2 tested methamphetamine (MA; 20 mg versus placebo; initial N = 19) on feelings of connectedness during a semi-structured 45-minute conversation with a previously unknown, same-sex partner. Salivary oxytocin and cardiovascular and subjective measures were also obtained to explore physiological correlates and the pharmacological specificity of any pro-social effects.
Two separate studies were run in parallel cohorts. Both used a within-subject, double-blind, placebo-controlled crossover design in which participants completed two laboratory sessions (drug and placebo) spaced at least 3–4 days apart. Study 1 administered MDMA 100 mg versus placebo; Study 2 administered methamphetamine 20 mg versus placebo. Capsules for active drugs and placebo were opaque and visually matched. Participants were informed their capsule might contain placebo, a stimulant, a sedative, or a hallucinogen to reduce expectancy effects. Healthy men and women aged 18–35 were recruited and screened with physical exam, ECG, psychiatric interview, medical and drug-use history and the SCL-90R. Exclusion criteria included cardiovascular abnormalities, current DSM-V diagnoses of substance dependence or mood, anxiety or psychotic disorders, past treatment for drug or alcohol use disorder, and pregnancy. Additional inclusion criteria were BMI 19–30, fluency in English and limited recent alcohol/caffeine consumption. For Study 1 only, lifetime MDMA use of 1–40 times was required. Written informed consent was obtained and procedures were approved by the institutional review board. Sessions ran 4.5 hours from morning. After arrival and abstinence verification by urinalysis and breath alcohol test, baseline subjective and cardiovascular measures were obtained. Participants ingested the capsule at 9:30 am and, at the expected peak window (70–115 minutes post-dose), engaged in a 45-minute semi-structured ‘‘small talk’’ conversation with a previously unknown, same-sex partner who was blind to drug condition and trained to interact naturally. Conversations were audiotaped. Subjective measures (Drug Effects Questionnaire, Visual Analog Scales for multiple adjectives, Profile of Mood States) and cardiovascular measures were taken repeatedly; a single saliva sample for oxytocin was collected at 120 minutes post-dose. At session end participants completed questionnaires assessing connection and closeness (Conversation Questionnaire, Connection During Conversations Scale (CDCS) with four subscales, and the Inclusion of Other in Self (IOS) single-item), and one-week online follow-up ratings of the two conversations and partners. Data were analysed separately for the two studies. Primary outcomes were the conversation rating questionnaires completed at end-of-session; analyses used mixed-model ANOVAs with drug condition as the within-subject factor and sex and session order as between-subject factors. Repeated subjective and cardiovascular measures were reduced to peak change from baseline and compared with paired t-tests. Pearson correlations assessed relationships between oxytocin (drug minus placebo) and closeness ratings. Significance was set at p < 0.05. The extracted text does not clearly report the final analysed sample sizes after exclusions for every analysis.
Two participants were excluded from analysis of Study 1 (one for strong negative feelings about a partner and one for socialising with a partner before follow-up); the initial sample sizes were N = 18 (MDMA study) and N = 19 (MA study). Demographically most participants were in their twenties with some college education and low-to-moderate prior drug use; Study 1 participants reported higher lifetime stimulant use consistent with the MDMA-use inclusion criterion. Primary social outcomes, end-of-session: In Study 1 (MDMA), there were no significant interactions with sex or order. Relative to placebo, MDMA significantly increased ratings of liking the conversation partner (F1,13 = 8.2, p = 0.01, ηp2 = 0.39), enjoyment of the conversation (F1,13 = 7.1, p = 0.02, ηp2 = 0.36) and meaningfulness of the conversation (F1,13 = 8.9, p = 0.01, ηp2 = 0.41). On the IOS there was a trend toward greater connection (F1,13 = 4.7, p = 0.05, ηp2 = 0.27). On the CDCS, MDMA increased several partner-related items (e.g., ‘‘They were interested in my thoughts and feelings’’, F1,13 = 7.7, p = 0.02, ηp2 = 0.37) and raised subscale scores for partner responsiveness (F1,13 = 15.4, p = 0.002, ηp2 = 0.54) and participant interest (F1,13 = 5.4, p = 0.04, ηp2 = 0.30). In Study 2 (MA), there were no systematic sex or order effects. Compared to placebo, MA increased ratings of conversational enjoyment (F1,15 = 13.8, p = 0.002, ηp2 = 0.48) and meaningfulness (F1,15 = 6.3, p = 0.02, ηp2 = 0.30), liking of the partner (main effect F1,15 = 15.2, p = 0.001, ηp2 = 0.50), perceived partner liking of the participant (F1,15 = 9.1, p = 0.009, ηp2 = 0.38) and closeness (F1,15 = 10.9, p = 0.005, ηp2 = 0.42). MA also increased IOS scores (F1,15 = 8.6, p = 0.01, ηp2 = 0.36) and several CDCS items and all four CDCS subscales, including shared reality (F1,15 = 7.2, p = 0.02, ηp2 = 0.32) and affective experience (F1,15 = 18.5, p = 0.001, ηp2 = 0.55). MA decreased ratings on several negative conversation items (for example ‘‘I thought they were boring’’, F1,15 = 14.7, p = 0.002, ηp2 = 0.49). Subjective drug effects and mood: On the DEQ both drugs increased ‘‘feel drug’’, ‘‘like drug’’, ‘‘high’’ and ‘‘want more’’. On VAS measures both MDMA and MA increased ratings of stimulated, insightful, sociable, loving and friendly. MDMA uniquely elevated feelings of trusting, appreciated, grateful and loved; MA uniquely increased feelings of being understood. On the POMS both drugs increased elation, friendliness and vigour; MDMA increased anxiety and confusion while MA reduced fatigue. End-of-session identification rates showed most participants identified active drugs as stimulants (MDMA: 75% identified MDMA as stimulant; MA: 74% identified MA as stimulant). Follow-up (one week): In Study 1 participants reported the MDMA conversation as more meaningful than the placebo conversation (F1,12 = 5.8, p = 0.03, ηp2 = 0.33). In Study 2 participants reported the MA conversation as more enjoyable (F1,15 = 22.6, p = 0.0003, ηp2 = 0.60), more meaningful (F1,12 = 12.9, p = 0.003, ηp2 = 0.46), and they reported greater liking and closeness to MA partners on follow-up. Ratings of partners and perceptions: After MDMA participants rated their partners as more physically attractive (F1,12 = 5.5, p = 0.04, ηp2 = 0.31) and warmer. Participants also reported that MDMA partners would perceive them as less competent but more warm. After MA participants reported their MA partners as warmer and believed MA partners perceived them as more intelligent, kind and warm. Physiological and oxytocin measures: Both drugs increased systolic and diastolic blood pressure and heart rate relative to placebo. Mean salivary oxytocin was higher after both MDMA and MA compared with placebo, but many samples were below the assay detection limit. In Study 1, 12 of 17 placebo samples were below detectability and 1 of 17 MDMA samples were below detectability; in Study 2, 18 of 19 placebo and 9 of 19 MA samples were below detectability. Undetectable samples were set to the assay lower limit (0.313 pg/mL). Oxytocin correlations: Drug-minus-placebo oxytocin changes correlated positively with drug-minus-placebo closeness ratings in the MDMA study (p = 0.03) but not in the MA study (p = 0.8). No significant correlations were found between oxytocin and heart rate for either drug. The extracted text does not provide confidence intervals for these correlations.
Molla and colleagues interpret their findings as demonstrating that MDMA robustly increases perceived connection and the meaningfulness of a brief in-person conversation with a stranger, and that methamphetamine produced a surprisingly similar increase in feelings of closeness and enjoyment. They highlight that these effects were evident during an actual dyadic interaction tested under double-blind conditions, extending prior work that mostly used indirect or computerised social tasks or self-report in group settings. The authors consider several possible mechanisms. For MDMA, they note prior evidence that the drug alters socioemotional processing — for example by changing recognition of emotional facial expressions, increasing neural responses to positive stimuli, and enhancing explicit and implicit empathy — and suggest these changes could make social encounters feel more rewarding. MDMA also produced a larger increase in salivary oxytocin and oxytocin changes correlated with closeness ratings after MDMA but not after MA, consistent with a serotonin–oxytocin pathway for some of MDMA's pro‑social effects. For MA, they propose that dopaminergic and noradrenergic actions might instead underlie increased attentiveness and reduced negative conversational aspects, thereby indirectly enhancing perceived connection. The authors candidly discuss limitations that constrain interpretation. The two studies were not directly comparable: only one dose of each drug was tested and participants in the MDMA study were required to have prior MDMA experience while most in the MA study were not. Salivary oxytocin measurement was particularly problematic — only a single post-dose sample was collected, many samples were below assay detection limits and no baseline oxytocin sample was obtained — making conclusions about oxytocin preliminary. Molla and colleagues also note that other measures of connectedness (including broader constructs like connectedness to self or the world) were not assessed and could be informative in future work. Finally, the authors outline implications without overstating them. They suggest enhanced patient–therapist connectedness might be one mechanism by which MDMA facilitates psychotherapy, that connectedness could serve as a measurable target in therapy protocols, and that findings warrant exploration of whether other drugs might also facilitate therapeutic relationships. They recommend future studies to compare drugs directly, test dose-response relationships, obtain more sensitive and repeated oxytocin measures, and investigate how different social contexts modulate drug effects. The procedure used here is presented as a useful model for studying pharmacological modulation of real-life social interaction.
Studies 1 and 2 were analyzed separately. The primary outcome measures were the three conversation rating questionnaires completed at the end of each session. Each question was analyzed separately because individual questions addressed different aspects of the interaction, and it was not known how drugs would affect each question. Mixed model analysis of variance (ANOVA) was conducted using drug condition as a within-subject variable, and sex and condition order (drug-placebo, placebo-drug) as between subject factors (SPSS Version 25), for each item. Sex and drug order were included as factors because the influence of sex and test-retest reliability on this task were not known. For subjective and cardiovascular measures taken repeatedly throughout each session, we calculated the peak change from baseline (pre-drug) on each session and compared drug vs. placebo scores using two-tailed paired t-tests (SPSS Version 25) within each study. Pearson correlations (SPSS Version 25) were conducted to determine the relationship between oxytocin levels and closeness ratings. The criterion for significance was p < 0.05.
As hypothesized, MDMA led to a robust increase in feelings of connection to conversation partners relative to placebo. Participants reported that they liked their partners more, and the conversations were more meaningful after MDMA. Interestingly, and contrary to our expectations, feelings of connectedness and enjoyment of the conversation were also increased by MA. Unfortunately, many of the oxytocin levels were below detectable limits, making it difficult to draw conclusions about these results. Nevertheless, MDMA and, to a lesser extent, MA increased salivary oxytocin levels, and oxytocin levels after MDMA (but not MA) were positively related to ratings of closeness with the partner. Taken together, these findings illustrate a novel method for assessing the effects of drugs on social connection, and yield the surprising finding that both MDMA and MA produce strong feelings of connectedness with a stranger after a brief conversation. The increased feelings of closeness and connectedness during a social interaction may contribute to the drugs' nonmedical use, and may also contribute to the effect of MDMA as an adjunct to psychotherapy. In Study 1, MDMA increased participants' ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful. This finding extends previous anecdotal reports, and some laboratory studies, reporting pro-social effects of MDMA on behavioral tasks with a social component. In prior studies, MDMA enhanced behavioral responses to emotional faces, increased subjective feelings of sociability and friendlinessand produced feelings of closeness, trust, and openness. However, no previous studies have examined the direct effect of MDMA on social connectedness in an in-person, socially relevant context, under double blind conditions. Our results show that the drug enhances the perceived quality and depth of a real-life social encounter. The behavioral and neural mechanisms by which MDMA enhances social interactions are not known. The drug may alter processing of emotional states of others, such as the ability to recognize negative emotional facial expressions and the neural responses to negative stimuli. MDMA also enhances ventral striatal responses to positive facial expressionsand increases explicit and implicit emotional empathy toward others. These MDMA induced alterations in socioemotional processing may create a more positive environment during interpersonal interactions, resulting in a more rewarding interaction and enhanced feelings of connection. Surprisingly, we found similar increases in ratings of closeness and connection to conversation partners, as well as enjoyment of the conversation after MA. This finding was contrary to our expectation that feelings of connectedness during an interpersonal encounter would be specific to MDMA. Although stimulants such as d-amphetamine and methamphetamine have been found to increase self-ratings of feeling social and talkative, to increase the amount of talking, and to improve ability to detect emotions in others, prototypic stimulants are not typically thought to promote feelings of closeness and connection. Until now, no studies have examined this social effect of drugs, and the present findings suggest that MA may share this effect with MDMA. Indeed, this finding raises questions about the nature of closeness and connection. For example, the commonalities between MDMA and MA on increased feelings of closeness raise the possibility that feelings of connectedness are related to the quantity or the quality of verbal interaction, rather than an underlying emotional connectedness. That is, increased verbal communication may indirectly facilitate interaction and even personal disclosure during a conversation. In the present study, the enhanced meaningfulness of the conversation induced by MDMA and MA were still present at least one week after the conversations. This suggests that interpersonal events experienced under the influence of a drug could have lasting effects on social interactions. Indeed, although we were unable to compare the two drugs directly, the lasting effects appeared to be more pronounced after MA compared to after MDMA. Whether this reflects true differences between the drugs will be determined in future studies. The present findings with MDMA and MA can be compared to a recent study conducted in our laboratory, examining feelings of connectedness after shallow conversations (such as that used here) and deep conversations, as designed by Aron et al.In the deep conversations, participants discussed topics that were more personally significant. In that study, in which no drugs were administered, the deep conversation increased reports of feeling connected relative to the shallow conversations. Interestingly, the increased reports of feeling connected after the deep conversations were comparable in magnitude to the increased reports of feeling connected after MDMA and MA in the present report. It will be of interest in the future to determine what aspects of the conversations are associated with feelings of connection. The results with oxytocin are difficult to interpret for several reasons. First, we obtained just a single sample on each session, and no sample before drug administration. More importantly, the assay used to assess salivary oxytocin was not sensitive enough, and many of the samples were below detectable limits. Even within these constraints, however, MDMA, and to a lesser extent MA, increased oxytocin levels. Interestingly, oxytocin levels after MDMA were related to feeling close to the partner, whereas oxytocin levels after MA were not. The robust increase in oxytocin after MDMA is consistent with other studies, and lesser effect of MA is consistent with previous reports that MA has little effect on oxytocin levels. The correlation between oxytocin levels and ratings of partner closeness after MDMA is consistent with the idea that feelings of closeness may be partly influenced by its serotonin-mediated effects on oxytocin. The lack of correlation between oxytocin and closeness after MA suggests that other actions of this drug (e.g., dopaminergic and noradrenergic), may mediate the closeness effect. Interestingly, MA, but not MDMA, increased participants' reports of attentiveness during the interaction and decreased their ratings of negative aspects of the conversation (e.g., difficulty in communication, and feeling drained of energy from the interaction). These results might reflect the relatively stronger effect of MA, compared to MDMA, on dopamine function. Future pharmacological studies with specific receptor agonists or antagonists agents may elucidate the contributions of various monoaminergic neurotransmitters for each drug. The results of this study have implications for MDMA-assisted therapy. First, they raise the possibility that some of the therapeutic effects of MDMA are related to enhanced feelings of connectedness between the patient and therapist. This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration. Second, the construct of connectedness may be of value in designing MDMA-assisted therapy protocols, providing a measurable target to assess patient-therapist interactions. Third, the findings with MA raise the interesting question of whether drugs other than MDMA might also facilitate psychotherapy, by affecting the quality of the patient-therapist connection. More broadly, understanding the behavioral processes by which MDMA enhances social interactions is important to help therapists optimize the beneficial effects of the drug. This project had limitations. First, the two studies were not directly comparable. Only a single dose of each drug was tested, making it difficult to compare across drugs. Further, all participants in Study 1 had used MDMA at least once in their lifetime whereas few of the participants in Study 2 reported prior MDMA use. It is unlikely that the prior drug use history contributed to responses in these two studies, as we have shown previouslythat history of prior MDMA has little effect on acute responses to the drug. We are not aware of studies examining the effects of MDMA or other stimulant drugs on acute responses to MA. Nevertheless, it is not known whether this difference in prior drug use contributed to the present findings. Another major limitation is that many of the saliva samples from placebo sessions had undetectable levels of oxytocin, and for these samples the minimum threshold value was used to calculate oxytocin levels. Therefore, our findings are considered preliminary, and the magnitude of salivary oxytocin detected may not reflect true physiological values. Future studies using more sensitive methods for measuring oxytocin levels are needed. Another limitation is that saliva samples for oxytocin detection were only collected once post-capsule administration without a baseline measurement, while it is known that baseline oxytocin concentrations vary from day to day. Finally, we used several validated measures of connection, but other measures of this construct, including scales assessing broader dimensions of connectedness to self and to the worldmay also be useful for future studies. In conclusion, the present study found that, relative to placebo, both MDMA and MA promoted feelings of connectedness to strangers during controlled social interactions. Although this effect was expected for MDMA, it was surprising that MA produced similar effects. MDMA is known for its prosocial effects (e.g., at rave parties, and facilitating interactions with therapists), whereas MA is known mainly as a treatment for ADHD and obesity, and for its abuse liability. Yet, in the present study, when participants were tested in the same social setting, the drugs produced similar effects. The unexpected finding that MA also increased feelings of closeness raises the novel possibility that this drug also might have potential as an adjunct to psychiatric treatment. An important future direction will be to investigate how social contexts alter responses to these drugs. The procedure used here offers a good model to study such effects.
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