3,4-Methylenedioxymethamphetamine (MDMA) is known for its pro-social effects, including feelings of connectedness. These effects contribute to its recreational use and potential therapeutic value as an adjunct to psychotherapy, particularly in treating PTSD. However, the behavioral processes underlying MDMA's impact on social interactions are not well-understood. This study aimed to investigate how MDMA influences feelings of connectedness during semi-structured conversations with unfamiliar partners. A secondary goal was to determine the pharmacological specificity of these effects by comparing MDMA's effects to those of methamphetamine (MA), a prototypical stimulant. The limited research on the direct effects of these drugs on real-life interpersonal interactions motivated this controlled laboratory study, which sought to provide a more nuanced understanding of the mechanisms through which these drugs alter social engagement. Understanding the prosocial effects is crucial for both understanding recreational use and potential therapeutic applications. While prior studies have shown prosocial effects of MDMA in both animals and humans, direct examination of its effect on feelings during real-life interactions is lacking. This study aimed to address this gap by using a controlled setting with dyadic conversations.

Existing literature demonstrates MDMA's prosocial effects in animals (increased social approach behaviors) and humans (increased sociability ratings and interaction time). Studies using computerized tasks also suggest MDMA affects socioemotional processing, impacting social function. While MDMA-assisted therapy patients report intensified trust and empathy, few studies directly examined MDMA's or other drugs' effects on behavior and feelings during real-life interactions. One study suggested stronger MDMA effects when participants were with others, but a controlled study of MDMA on social interactions in a double-blind setting with a specific measure of connectedness was lacking prior to this research. This study aimed to directly address this lack of data and to investigate whether the effect was specific to MDMA or generalizable to other stimulants.

Two separate double-blind, placebo-controlled studies were conducted. Study 1 (N=18) examined the effects of MDMA (100mg) and Study 2 (N=19) examined the effects of MA (20mg). Participants, healthy male and female volunteers (18-35 years), underwent rigorous screening. Both studies used a randomized, double-blind design with drug and placebo conditions. Following drug administration (MDMA or MA or placebo), participants engaged in a 45-minute semi-structured conversation with an unfamiliar same-sex partner. Subjective measures (Drug Effects Questionnaire [DEQ], Visual Analog Scale [VAS], Profile of Mood States [POMS]) and cardiovascular measures were obtained throughout the session. Saliva samples for oxytocin analysis were collected at the peak subjective drug effect (120 minutes). After the conversation, participants completed questionnaires assessing feelings of connectedness (Conversation Questionnaire, Connection During Conversations Scale [CDCS], Inclusion of Other in Self Scale [IOS]). A one-week follow-up assessed lasting effects. Data analysis involved mixed model ANOVA for conversation rating questionnaires and paired t-tests for subjective and cardiovascular measures. Pearson correlations assessed the relationship between oxytocin levels and closeness ratings. The conversation task involved a series of 'small talk' questions, designed to minimize potential ceiling effects in connectedness ratings. The small talk questions were designed to help detect the increase following drug administration. Participants and partners were blind to drug identity.

Both MDMA and MA significantly increased feelings of connection with conversation partners compared to placebo. This was evidenced by increased ratings on measures of liking the partner, finding the conversation enjoyable and meaningful, and feeling close to the partner. These effects were observed both immediately after the conversation and in a one-week follow-up. Specifically, in Study 1 (MDMA), MDMA significantly increased ratings on the Conversation Questionnaire (liking partner, enjoyment, meaningfulness) and on the IOS scale (trend towards greater connection). On the CDCS, MDMA increased ratings related to partner responsiveness and participant interest. In Study 2 (MA), MA significantly increased ratings on enjoyment and meaningfulness, liking the partner, perceived liking from the partner, and feeling close to the partner. On the CDCS, MA showed similar increases, and also decreased ratings of negative aspects of the conversation (e.g., difficulty communicating, feeling drained). Both MDMA and MA increased salivary oxytocin levels, although many samples were below detectable limits. However, oxytocin levels correlated positively with closeness ratings only after MDMA, not MA. Both drugs also increased systolic and diastolic blood pressure and heart rate. In the follow-up, the enhanced meaningfulness of the conversation after MDMA and MA persisted. Participants rated their MA partners as significantly warmer and more desirable compared to their placebo partners. Participants also reported wanting to spend significantly more time with their MA conversation partners compared to their placebo partners. The follow up showed MDMA participants rating their MDMA partners as more physically attractive and warm compared to placebo partners.

The study's findings confirm the hypothesis that MDMA increases feelings of connection during social interactions, providing evidence supporting anecdotal reports and some previous studies. The surprising finding was that MA produced similar effects. This challenges the assumption that feelings of connectedness are unique to MDMA's effects, and suggests that other mechanisms, potentially related to increased verbal interaction, could be at play. The persistent effects one week later suggest lasting impacts of drug-influenced interpersonal events. The oxytocin results are complex, partly due to the assay's limitations. While both drugs increased oxytocin, the correlation with closeness was only found with MDMA, suggesting different neurotransmitter systems may mediate the closeness effect for each drug. The stronger effect of MA on attentiveness and reduction of negative aspects of the conversation might reflect MA's relatively stronger effect on dopamine function compared to MDMA. Future research should use more sensitive oxytocin assays and investigate the role of specific neurotransmitter systems.

This study demonstrates that both MDMA and MA enhance feelings of connectedness during brief conversations with strangers. While expected for MDMA, the MA findings are novel and suggest potential for this drug in psychiatric treatment. The methodology provides a valuable model for future studies investigating social contexts and drug responses. Future research should explore the specific neurotransmitter mechanisms, including the use of receptor agonists/antagonists, and further examine the potential of MA as a therapeutic adjunct. This research also offers potential implications for MDMA-assisted therapy, particularly regarding the enhancement of patient-therapist connectedness.

The studies were not directly comparable due to using a single dose for each drug and differences in prior drug use experience. Many oxytocin samples had undetectable levels, and the sensitivity of the assay might have affected the results. Saliva samples were only collected once post-capsule administration without a baseline measurement. Future studies should use more sensitive methods for measuring oxytocin, including baseline measurements and a wider range of doses. Lastly, this study used a narrow range of measures of connectedness. Future studies could benefit from the use of additional scales to more fully investigate this construct.