The empathogen 3,4-methylenedioxymethamphetamine, but not methamphetamine, increases feelings of global trust

Psychedelic social psychology examines how substances that alter perception, mood and consciousness might influence social connection and subjective well being. Martinez and colleagues frame MDMA (3,4-methylenedioxymethamphetamine) as an "empathogen" with distinctive prosocial effects compared with other stimulants, and note meta-analytic evidence of moderate to large effects on sociability. Previous experimental work has mainly assessed MDMA's acute effects toward immediate interaction partners, leaving open whether these effects generalise to broader social targets such as one’s community or society. The present research tested whether MDMA or methamphetamine (MA) increase subjective well being and global social well being following a laboratory conversation task. Using two within subject, two-session studies, the investigators compared post‑conversation scores on selected subscales of the Comprehensive Inventory of Thriving (CIT) 1.5 hours after drug versus placebo. Study 1 compared 100 mg MDMA with placebo, and Study 2 compared 20 mg MA with placebo. The pre-registered hypotheses were that each drug would increase nine CIT subscales indexing support, trust, respect, belonging, engagement, self worth, meaning, optimism and life satisfaction relative to placebo.

Both studies used a within subject, double blind, two‑session design with counterbalancing. Each participant completed an orientation session, two in‑lab conversation sessions (one drug, one placebo) separated by at least four days, and a 1‑week online follow up. After the drug reached peak effect, participants engaged in a 45‑minute structured conversation with a same sex confederate who was not under the influence. The CIT was administered at orientation and immediately after each conversation session; the primary comparisons were post‑drug versus post‑placebo ratings assessed 1.5 hours after the conversation. Healthy volunteers aged 18–35 were recruited; screening included medical, psychiatric and ECG assessments. Exclusion criteria encompassed medical conditions requiring regular medication, current substance dependence or major psychiatric disorders, pregnancy, abnormal ECG, and other standard safety criteria. Study 1 additionally required participants to have used MDMA previously (between 1 and 40 times) without adverse effects; Study 2 did not require prior MA use. Participants provided informed consent under an Institutional Review Board approved protocol. Drugs were delivered in opaque capsules: Study 1 used 100 mg MDMA (Organix Inc.), Study 2 used 20 mg MA (Desoxyn, Lundbeck), and placebos contained inert filler. The CIT subscales analysed comprised nine three‑item scales (support, trust, respect, belonging, engagement, self worth, meaning, optimism, life satisfaction), each scored 1–5 and averaged per subscale. Cronbach's alpha values were reported in a table according to the extract, but specific alpha coefficients are not clearly reported in the extracted text. Analyses used two sets of two‑tailed dependent means t tests at alpha = 0.05: (1) within subject comparisons of post‑drug versus post‑placebo scores for each study, and (2) comparisons of gain scores from orientation to post‑drug versus orientation to post‑placebo. The authors note that multilevel or residualised change models were pre-registered but could not be estimated due to the modest sample sizes and the counterbalanced design, which also introduced variability in the time between orientation and the post‑drug session. Two participants were excluded from Study 1 (one for deviant conversational behaviour as rated by confederates and one for socialising with a confederate outside the study); no exclusions occurred in Study 2.

Study samples comprised 15 analysed participants in Study 1 (after two exclusions) and 20 in Study 2. Demographic summaries in the extracted text indicate a mean age of 26.7 years in Study 1 (53% male, 87% college or masters level education) and 22.8 years in Study 2 (45% male, 45% college or masters level education). Participants in Study 1 reported higher lifetime drug use than those in Study 2. Primary outcomes from Study 1 (MDMA versus placebo) showed a significant increase in global trust after MDMA compared with after placebo: t(14) = -2.583, p = 0.022. Corresponding gain score comparisons from orientation to post‑MDMA versus orientation to post‑placebo were likewise significant, t(14) = -2.582, p = 0.022. On average, trust increased from orientation to post‑MDMA by M = +0.18 (SD = 0.45) and decreased from orientation to post‑placebo by M = -0.07 (SD = 0.41). Self worth showed a marginal effect: post‑MDMA versus post‑placebo yielded t(14) = -2.000, p = 0.065, and the corresponding gain score comparison was marginal at the same level; mean change from orientation to post‑MDMA was M = +0.20 (SD = 0.57) versus orientation to post‑placebo M = -0.02 (SD = 0.54). No significant differences emerged for life satisfaction, optimism, meaning, belonging, support, respect or engagement in Study 1. Study 2 (MA versus placebo) produced no significant increases in any of the nine CIT subscales (trust, worth, life satisfaction, optimism, meaning, belonging, support, respect, engagement) for post‑MA versus post‑placebo or for gain scores from orientation. The extracted text notes other analyses from these data reported elsewhere: both MDMA and MA increased conversational enjoyment, perceived connection to the partner, and oxytocin levels, but only MDMA produced a significant correlation between oxytocin and perceived partner closeness in those additional reports. Those complementary findings are described in the Discussion but the present paper's primary reported results are the MDMA effect on global trust and marginal effect on self worth, and the null findings for MA.

Martinez and colleagues interpret their findings as evidence that MDMA uniquely increases a sense of global trust — that is, trust extending beyond an immediate interaction partner to broader social targets such as neighbourhoods, society and "most people" as indexed by the CIT. The authors argue these results extend prior work that documented MDMA's prosocial effects toward specific interaction partners and note that the marginal increase in self worth complements the trust finding by indicating enhanced feelings of value and social safety. The investigators situate potential mechanisms in oxytocinergic pathways, reporting that companion analyses found oxytocin increases after both drugs but a significant oxytocin–closeness relationship only after MDMA. They propose that such unique biological and subjective pathways may help explain why MDMA's social positivity may generalise beyond immediate dyads, while acknowledging that these mechanistic accounts remain speculative and require further research. Key limitations acknowledged by the authors include small sample sizes (Study 1 N = 15; Study 2 N = 20), differential recruitment criteria across studies (prior MDMA experience required in Study 1 but not for MA in Study 2) which could affect expectancies and self selection, and the decision to compare each drug separately to placebo rather than directly compare MDMA and MA within a single analytic model. The counterbalanced design, while intended to reduce expectancy effects, prevented estimation of growth trajectories and introduced variability in time between orientation and post‑drug assessments that could not be modelled. The authors also note uncertainty about the duration of the observed effects beyond the 1.5 hour post‑conversation assessment and that residual acute drug effects might have contributed to self reports. In terms of implications, the authors suggest the findings provide preliminary support for considering MDMA as a pharmacological tool to bolster social safety and broader social well being, which could have relevance for interventions targeting loneliness, social anxiety or impairments in social functioning. They emphasise the need for replication with larger samples, consistent inclusion criteria across comparative substances, designs that permit direct drug‑to‑drug comparisons and additional follow up time points to establish whether increases in global social positivity persist beyond the acute phase. The authors characterise their results as foundational evidence that MDMA, but not MA, increased feelings of global trust following a dyadic conversation.