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
8 affiliations
- 1Cognitive Neuroscience Unit, School of Psychology, Deakin University, Burwood, VIC, Australia
- 2School of Medicine and Psychology, The Australian National University, Canberra, ACT, Australia
- 3Monarch Mental Health Group, Sydney, NSW, Australia
- 4Integrative Psychology and Medicine, Melbourne, VIC, Australia
- 5La Trobe University, Melbourne, VIC, Australia
- 6Ikon Institute of Australia, Melbourne, VIC, Australia
- 7Peridot Clinic, Newcastle, NSW, Australia
- 8Department of Brain Sciences, Imperial College London, UK
Abstract
Background:: 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.
Methods:: 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 >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.
Results:: After dosing, both groups showed increased alpha to gamma WM-related oscillatory power (p < 0.001). After psilocybin, participants showed steeper WM-related aperiodic slopes (p = 0.018), an effect maximal in occipital electrodes (p < 0.001, Cohen’s d = 0.802, BF10 = 155.138), and significant in occipital electrodes during resting (p = 0.008). The MDMA group showed improved task accuracy in the post-dosing EEG session (p = 0.005, Cohen’s d = 0.561, BF10 = 7.809). Both groups showed improved accuracy at 3-months (p-holm < 0.001, Cohen’s d = 0.678, BF10 = 272.074).
Conclusions:: 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.
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BibTeX
@article{bailey2026evidence,
title = {{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}},
author = {Neil Wayne Bailey and Samantha Lee Webb and Bernadette Mary Fitzgibbon and Nigel Christopher Denning and Traill Dowie and Monica Margaret Schweickle and Anish Modak and Grace Chan and Jackie Knight and Molly Waldron and Kirsten Gainsford and Hannah Hawkes and Sonia Zammit and Novi Christina Sutanto and Kate Godfrey and Paul Bernard Fitzgerald},
journal = {Journal of Psychopharmacology (Oxford, England)},
year = {2026},
month = jul,
doi = {10.1177/02698811261464991},
url = {https://doi.org/10.1177/02698811261464991},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Neil Wayne Bailey
AU - Samantha Lee Webb
AU - Bernadette Mary Fitzgibbon
AU - Nigel Christopher Denning
AU - Traill Dowie
AU - Monica Margaret Schweickle
AU - Anish Modak
AU - Grace Chan
AU - Jackie Knight
AU - Molly Waldron
AU - Kirsten Gainsford
AU - Hannah Hawkes
AU - Sonia Zammit
AU - Novi Christina Sutanto
AU - Kate Godfrey
AU - Paul Bernard Fitzgerald
PY - 2026
DA - 2026/07/23
JO - Journal of Psychopharmacology (Oxford, England)
DO - 10.1177/02698811261464991
UR - https://doi.org/10.1177/02698811261464991
AB - Background:: 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. Methods:: 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 >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. Results:: After dosing, both groups showed increased alpha to gamma WM-related oscillatory power (p < 0.001). After psilocybin, participants showed steeper WM-related aperiodic slopes (p = 0.018), an effect maximal in occipital electrodes (p < 0.001, Cohen’s d = 0.802, BF10 = 155.138), and significant in occipital electrodes during resting (p = 0.008). The MDMA group showed improved task accuracy in the post-dosing EEG session (p = 0.005, Cohen’s d = 0.561, BF10 = 7.809). Both groups showed improved accuracy at 3-months (p-holm < 0.001, Cohen’s d = 0.678, BF10 = 272.074). Conclusions:: 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.
SN - 0269-8811
SN - 1461-7285
ER -