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No evidence for deleterious effects of psilocybin and MDMA on working memory or related neurophysiological activity in a non-clinical population: An uncontrolled exploratory study

delete2026-07-23
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PRE
AI
N
Neil W. Bailey
S
Samantha Lee Webb
B
Bernadette M. Fitzgibbon
N
Nigel Christopher Denning
T
Traill Dowie
M
Monica Margaret Schweickle
A
Anish Modak
G
Grace Chan
J
Jackie Knight
M
Molly Waldron
K
Kirsten Gainsford
H
Hannah Hawkes
S
Sonia Zammit
N
Novi Christina Sutanto
K
Kate Godfrey
P
Paul B. Fitzgerald
DOI:10.1177/02698811261464991delete
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Abstract

Abstract

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<jats:sec> <jats:title>Background:</jats:title> <jats:p>Research indicates psychedelics hold therapeutic potential, but possible deleterious effects have been insufficiently examined. We explored working memory (WM) performance and WM-related neurophysiological activity before and after exposure to psilocybin or 3,4-methylenedioxymethamphetamine (MDMA) in an uncontrolled study.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Healthy participants were exposed to a single dose of psilocybin or MDMA (data analysed from 29 participants for each drug, with 16 receiving both drugs after &gt;3-month washout). One to 16 days before and 5–16 days after dosing, participants completed a 3back WM task and eyes-closed resting with electroencephalography (EEG), plus a 3back during a 3-month remote follow-up.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> After dosing, both groups showed increased alpha to gamma WM-related oscillatory power ( <jats:italic toggle="yes">p</jats:italic>  &lt; 0.001). After psilocybin, participants showed steeper WM-related aperiodic slopes ( <jats:italic toggle="yes">p</jats:italic>  = 0.018), an effect maximal in occipital electrodes ( <jats:italic toggle="yes">p</jats:italic>  &lt; 0.001, Cohen’s <jats:italic toggle="yes">d</jats:italic>  = 0.802, BF <jats:sub>10</jats:sub>  = 155.138), and significant in occipital electrodes during resting ( <jats:italic toggle="yes">p</jats:italic>  = 0.008). The MDMA group showed improved task accuracy in the post-dosing EEG session ( <jats:italic toggle="yes">p</jats:italic>  = 0.005, Cohen’s <jats:italic toggle="yes">d</jats:italic>  = 0.561, BF <jats:sub>10</jats:sub>  = 7.809). Both groups showed improved accuracy at 3-months ( <jats:italic toggle="yes">p</jats:italic> -holm &lt; 0.001, Cohen’s <jats:italic toggle="yes">d</jats:italic>  = 0.678, BF <jats:sub>10</jats:sub>  = 272.074). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Our results are suggestive of enduring neurophysiological effects following a single dose of MDMA or psilocybin. Our results do not support concerns about cognitive impairments from single exposures to MDMA or psilocybin in controlled settings, suggesting clinical utility does not risk impairing WM. However, given the uncontrolled study design, future research is required to confirm our observations reflect drug-induced neurophysiological changes.</jats:p> </jats:sec>

Journal

Journal of Psychopharmacology cover
Journal of Psychopharmacology
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5.5
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imperial college london
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monarch mental health group
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the australian national university
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Deakin University
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