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Understanding the Psychological Effects of Psilocybin and 3,4-Methylenedioxymethamphetamine in a Non-Clinical Population

Paul B. Fitzgerald, Sara Webb, Nigel Christopher Denning, Tra-Ill Dowie, Monica Schweickle, Anish Modak, Grace J Chan, Jeffrey Knight, Molly Waldron, Kirsten Gainsford, H.a. Hawkes, Stanley Zammit, Novi Christina Sutanto, Bernadette M. Fitzgibbon, Neil W. Bailey

medRxiv May 29, 2025 preprint DOI: 10.1101/2025.05.28.25328532 via OpenAlex

Summary

AI-generated from the abstract

A single dose of psilocybin, but not MDMA, produced short-term psychological changes in healthy adults: reduced neuroticism, increased extraversion, and improvements in mindfulness and connectedness one week after dosing. Psilocybin also induced stronger mystical experiences than MDMA, and the magnitude of those experiences correlated with changes in connectedness and mindfulness, though not with personality changes. Participants preferred larger group settings for MDMA than for psilocybin. The findings suggest that psilocybin's psychological effects may be mediated by mystical-type experiences.

Study at a glance

Characteristics Controlled trial
Sample size 48
Population Healthy individuals
Interventions Psilocybin MDMA
Duration Single dose, assessments at baseline, 1-3 days post dose, one week post dose, and 3 month follow up (3 month data not included)
Topics Psilocybin
Keywords Hallucinogen Population Clinical psychology Psychotherapist
Citations 2
Key finding Psilocybin, but not MDMA, produced significant short-term reductions in neuroticism, increases in extraversion, and improvements in mindfulness and connectedness, with mystical experiences mediating changes in connectedness and mindfulness.

Abstract

Abstract Objective Despite many decades of experimental studies and clinical trials involving a variety of psychedelic agents, we still lack a comprehensive understanding of the effects of these substances on psychological experiences. As such, we designed and conducted a study to comprehensively characterise the effects of both psilocybin and 3,4-Methylenedioxymethamphetamine (MDMA) on a range of psychological outcomes in a substantive non-clinical population. Methods This study involved a single dose administration of psilocybin or MDMA in healthy individuals in a group setting (2-4 people per session). All participants underwent a single preparation session, a drug exposure session, and an integration session within 72 hours of dosing. Outcome assessments were conducted at a pre-dosing baseline, 1-3 days post dose (side effects only), one week post dose and at 3 month follow up (the later time point data is not included here). Results Of 48 participants, 25 initially received MDMA and 23 psilocybin. Ten cross-over participants received MDMA and then psilocybin and six participants received both in the reverse order: making a total of 31 MDMA and 33 psilocybin dosing sessions. In the week after dosing, we found significant changes in personality (a reduction in neuroticism and increase in extraversion), mindfulness, and connectedness following the administration of psilocybin but not MDMA. Psilocybin also produced significantly stronger mystical experiences compared to MDMA, and there was a significant correlation between the magnitude of these mystical experiences and changes in connectedness and mindfulness (but not changes in personality). Of note, participants seemed more comfortable with, and preferred, larger group sizes when being administered MDMA than psilocybin. Discussion Our results identified a range of short-term psychological effects in non-clinical participants following a single dose of psilocybin, that were not reported following a single dose of MDMA. Notably, our results indicate that these effects following psilocybin may be moderated through its induction of mystical experiences, as has been previously hypothesised. Although preliminary, our results also suggest that larger group dosing sessions seem more feasible with MDMA than psilocybin.

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