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.

In the last 3 years PBF has received equipment for research from Neurosoft, Nexstim and Brainsway Ltd. He has served on scientific advisory boards for Magstim and LivaNova and received speaker fees from Otsuka. He has also acted as a founder and board member for TMS Clinics Australia and Resonance Therapeutics. PBF is supported by a National Health and Medical Research Council of Australia Investigator grant (1193596). The other authors declare that they have no conflicts of interest.

ACTRN12622001535763p

This study was funded through a donation to the Australian National University from Mind Medicine Australia. PBF is supported by a National Health and Medical Research Council of Australia Practitioner Fellowship (6069070).

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ACT Health Human Ethics Committee gave ethical approval for this work

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paul.fitzgeraldanu.edu.au, Samantha.webbanu.edu.au, nigel.denningintegrativepsychology.net.au, trailldowiehotmail.com, monica.schweicklethepsychedelicconsultancy.com, amodakmmhg.com.au, gchanmmhg.com.au, jackiejackieknight.com, Molly.Waldronanu.edu.au, Kirsten.gainsfordanu.edu.au, hhawkes.psychologygmail.com, Sonia.Zammitchoicesmindandbody.com, novisutantopsychologygmail.com, bernadette.fitzgibbonanu.edu.au, neil.baileyanu.edu.au

The de-identified data that support the findings of this study are available from the corresponding author, PBF, upon reasonable request.