TY - JOUR
T1 - The effects of psilocybin on cognitive and emotional functions in healthy participants
T2 - Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation
AU - Rucker, James J
AU - Marwood, Lindsey
AU - Ajantaival, Riikka-Liisa J
AU - Bird, Catherine
AU - Eriksson, Hans
AU - Harrison, John
AU - Lennard-Jones, Molly
AU - Mistry, Sunil
AU - Saldarini, Francesco
AU - Stansfield, Susan
AU - Tai, Sara J
AU - Williams, Sam
AU - Weston, Neil
AU - Malievskaia, Ekaterina
AU - Young, Allan H
N1 - Funding Information:
The authors thank Katrin Preller for technical advice and support, and also acknowledge the support of the following individuals in the completion of this research: Frederick Reinholdt, Peter Gasser, Nefize Yalin, Dimosthenis Tsapekos, Kristina Posadas, Aster Daniel, Glynis Ivin, Sophie Ward, Michael Welds, Martin Heasman, Elizabeth Hodges and Rafaela Giemza. The authors acknowledge support of the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, and the NIHR/Wellcome Trust Clinical Research Facility at King’s College Hospital, where this study was undertaken. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Medical writing support, under the direction of the authors, was provided by Ottilie Gildea of CMC AFFINITY, McCann Health Medical Communications Ltd., in accordance with Good Publication Practice (GPP3) guidelines. This assistance was funded by COMPASS Pathways plc, London, UK.
Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JJR is supported by a Clinician Scientist Fellowship (CS-2017-17-007) from the National Institute for Health Research (UK) and has received grant and congress funding from COMPASS Pathways. AHY’s research is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. AHY has also received grant funding from COMPASS Pathways plc and honoraria for attending advisory boards and presenting lectures for Allergan, AstraZeneca, Bionomics, Eli Lilly, Janssen, LivaNova, Lundbeck, Servier, Sumitomo Dainippon Pharma and Sunovion; and has received consulting fees from Johnson & Johnson and LivaNova. AHY is on the Editorial Advisory Board at the Journal of Psychopharmacology. R-LJA has received research funding and consulting fees from COMPASS Pathways plc. CB has received research funding from COMPASS Pathways plc. JH reports personal fees from AlzeCure, Aptinyx, AstraZeneca, Athira Therapeutics, Axon Neuroscience, Axovant, Biogen Idec, BlackThornRx, Boehringer Ingelheim, Brands2life, Cerecin, Cognition Therapeutics, COMPASS Pathways plc, Corlieve, Curasen, EIP Pharma, Eisai, Eli Lilly, FSV7, G4X Discovery, GfHEU, Heptares, Kaasa Health, Ki Elements, Lundbeck, Lysosome Therapeutics, MyCognition, Neurocentria, Neurocog, Neurodyn Inc., Neurotrack, Novartis, Nutricia, Probiodrug, Regeneron, ReMynd, Rodin Therapeutics, Samumed, Sanofi, Servier, Signant, Syndesi Therapeutics, Takeda, Vivoryon Therapeutics, vTv Therapeutics and Winterlight Labs. ML-J, LM, SM, FS, SS, SW, HE and EM are employees or former employees of COMPASS Pathways plc. SJT has received consulting fees from COMPASS Pathways plc and is an advisor for Clerkenwell Health and Albert Labs. NW has no disclosures to make in relation to this work.
Funding Information:
The authors thank Katrin Preller for technical advice and support, and also acknowledge the support of the following individuals in the completion of this research: Frederick Reinholdt, Peter Gasser, Nefize Yalin, Dimosthenis Tsapekos, Kristina Posadas, Aster Daniel, Glynis Ivin, Sophie Ward, Michael Welds, Martin Heasman, Elizabeth Hodges and Rafaela Giemza. The authors acknowledge support of the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King?s College London, and the NIHR/Wellcome Trust Clinical Research Facility at King?s College Hospital, where this study was undertaken. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Medical writing support, under the direction of the authors, was provided by Ottilie Gildea of CMC AFFINITY, McCann Health Medical Communications Ltd., in accordance with Good Publication Practice (GPP3) guidelines. This assistance was funded by COMPASS Pathways plc, London, UK. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored and funded by COMPASS Pathways plc, London, UK.
Publisher Copyright:
© The Author(s) 2022.
PY - 2022/1
Y1 - 2022/1
N2 - Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin’s effects on cognitive function have not been widely or systematically studied. Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. Methods: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session. Results: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. Conclusions: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. Clinical Trial Registration: EudraCT (https://www.clinicaltrialsregister.eu/) number: 2018-000978-30.
AB - Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin’s effects on cognitive function have not been widely or systematically studied. Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. Methods: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session. Results: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. Conclusions: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. Clinical Trial Registration: EudraCT (https://www.clinicaltrialsregister.eu/) number: 2018-000978-30.
KW - cognition
KW - emotional processing
KW - placebo-controlled
KW - Psilocybin
KW - randomised clinical trial
UR - http://www.scopus.com/inward/record.url?scp=85122318558&partnerID=8YFLogxK
U2 - 10.1177/02698811211064720
DO - 10.1177/02698811211064720
M3 - Article
C2 - 35090363
AN - SCOPUS:85122318558
SN - 0269-8811
VL - 36
SP - 114
EP - 125
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
IS - 1
ER -
