Rapid Effects of MDMA Administration on Self-Reported Personality Traits and Affect State: A Randomized, Placebo-Controlled Trial in Healthy Adults

Maples-Keller and colleagues situate their study within growing interest in MDMA as a psychotherapeutic adjunct and a literature on serotonergic psychedelics producing lasting changes in personality and affect. Earlier research has shown that classic psychedelics (for example, psilocybin and LSD) can increase Five-Factor Model (FFM) Openness and sometimes decrease Neuroticism or increase Extraversion, often assessed months to a year after administration. By contrast, controlled trials specifically testing MDMA’s effects on personality and affect in healthy adults are limited; much prior work has relied on cross-sectional comparisons of recreational users and non-users or clinical samples receiving psychotherapy alongside drug administration, leaving uncertainty about MDMA’s independent, short-term impact on trait and state measures. This pre-registered, secondary analysis tests whether a single 100 mg dose of MDMA, administered in a randomised, placebo-controlled laboratory trial of psychiatrically and medically healthy adults (N = 34), produces rapid changes in FFM domains and affective state at approximately 48 hours post-administration. The investigators specified four directional hypotheses: MDMA (versus placebo) would produce greater decreases in Neuroticism and Negative Affect, and greater increases in Openness and Positive Affect. The study aims to characterise short-term personality and affective shifts that could plausibly operate as mechanisms in MDMA-assisted psychotherapy and to provide effect-size estimates for future work.

This analysis used data from a randomised, placebo-controlled laboratory trial originally designed to assess fear extinction retention; the present report is a secondary analysis focused on personality and affect. Participants were 34 psychiatrically and medically healthy adults aged 21–55 who reported prior recreational MDMA use (mean lifetime uses ≈ 3.74). The sample was predominantly male (70.6%) and largely White (70.6%). All procedures were IRB approved. Study visits occurred on three consecutive days. Baseline assessments (Visit 1) included the IPIP-NEO-60 to index FFM domains (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness) and the PANAS-X to measure current Positive and Negative Affect and subscales. On Visit 2 participants received either 100 mg MDMA or an inactive placebo in identical capsules; blinding was preserved for study staff except the study physician. No psychotherapy or formal therapeutic support was provided during drug administration sessions; participants were encouraged to sit with their experience and were offered a music playlist and drawing materials. Follow-up assessments of IPIP-NEO-60 and PANAS-X occurred on Visit 3, about 48 hours after drug administration (72 hours after baseline). The primary trial’s outcome was fear extinction recall, and further procedural/exclusion details are reported elsewhere. Change scores were computed as Visit 3 minus Visit 1 for each scale. Because variances differed across groups, the investigators used Welch’s two-sample independent t-tests to compare mean change between MDMA and placebo groups. Four directional, a priori hypotheses were tested and corrected for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR); an additional 10 nondirectional exploratory tests were conducted and reported with uncorrected p-values. Significance was set at p < .05. Power calculations for this secondary analysis indicated 80% power to detect effect sizes of d = 0.87 for one-tailed tests of the directional hypotheses and d = 0.99 for two-tailed exploratory tests, values informed by prior literature.

Overall, mean change from baseline to ~48 hours post-administration in self-reported personality and affect did not reach statistical significance for the four pre-specified hypotheses after correction. The paper reports that the four directional Welch’s t-tests and the 10 exploratory t-tests yielded no statistically significant group differences at the pre-set threshold. Exact p-values and confidence intervals are not clearly reported in the extracted text. Despite the lack of statistical significance, several effect-size differences are highlighted. The MDMA group showed medium-sized increases versus placebo in FFM Openness (d = 0.79) and PANAS-X Positive Affect (d = 0.51) at 48 hours post-administration. Medium effects were also observed for FFM Agreeableness and the PANAS-X Joviality subscale (ds = 0.55 and 0.56, respectively). Smaller effects were noted for PANAS-X Self-Assurance, Attentiveness, and Sadness, though these did not reach significance. The authors indicate that tables and figures (referenced but not included in the extracted text) present the detailed test results for all 14 comparisons.

The investigators interpret the findings as preliminary evidence that a single 100 mg dose of MDMA may produce short-term increases in Openness and Positive Affect in psychiatrically healthy adults, even in the absence of psychotherapy. They note that the medium effect sizes for Openness (d = 0.79) and Positive Affect (d = 0.51) align with literature reporting that psychedelic experiences can lead to heightened creativity, imagination and elements of self‑transcendent experience. At the same time, the study did not replicate prior reports of reductions in trait Neuroticism or state Negative Affect, and no statistically significant differences were observed for the a priori hypotheses after correction. Several limitations acknowledged by the authors could account for the null inferential results and affect interpretation. First, the sample was small and may have been underpowered to detect true effects smaller than those assumed in power calculations; this raises the possibility of both type II error and imprecise or inflated effect-size estimates. Second, the sample was demographically narrow (predominantly male, largely White) and restricted to participants with prior MDMA experience, which may limit generalisability and could compromise blinding. Third, follow-up was brief (48 hours post-dose), so the durability of any trait or affective changes is unknown. The authors also note the absence of a manipulation check asking participants which capsule they believed they received. In terms of implications, the paper suggests that MDMA may shift affect and interpersonal-related traits toward a more open, affiliative, and positive affective style in the short term, and that these rapid changes could be relevant mechanisms for MDMA-assisted psychotherapy. The authors call for larger, demographically diverse, and clinically representative trials with longer follow-up periods, routine inclusion of personality assessment in clinical trials, direct comparisons across psychedelic compounds, and investigation of moderators of effect size. Safety observations from the parent trial are reported as consistent with existing clinical research: no negative or iatrogenic psychological consequences were detected within the assessed time windows, and MDMA was well tolerated in this sample.

The study offers pre-registered, placebo-controlled data indicating that medium-to-large effect sizes may be observed for increases in Openness and state Positive Affect approximately 48 hours after a single 100 mg dose of MDMA in healthy adults. While statistical significance was not achieved for the primary hypotheses—likely due to limited sample size and short follow-up—the findings provide effect-size estimates to inform future, better-powered trials. The authors conclude that clarifying the magnitude, duration, and moderators of MDMA’s effects on personality and affect will be important for optimising therapeutic delivery and for informed consent in clinical settings.