The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation
In the largest randomised, double‑blind, placebo‑controlled phase 1 trial of psilocybin to date (n=89), healthy participants received a single oral dose of 10 mg or 25 mg psilocybin (or placebo) simultaneously in small groups with one‑to‑one psychological support. Both doses were generally well tolerated with no serious adverse events and produced no clinically relevant short‑ or long‑term differences in cognitive performance (CANTAB global and domain scores) or emotional processing compared with placebo.
Authors
- James Rucker
- Allan Young
- Ekaterina Malievskaia
Published
Abstract
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.
Research Summary of 'The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation'
Introduction
Psilocybin is a naturally occurring psychedelic and a partial agonist at serotonin receptors, principally 5-HT2A and 5-HT1A. Earlier clinical and preclinical studies have suggested psilocybin can produce rapid changes in mood and affect and may reduce symptoms in conditions such as treatment-resistant depression, anxiety in terminal illness, OCD and substance use disorders. However, much of the evidence to date has come from small, often open-label studies or trials lacking placebo control, and there remains limited systematic evidence about psilocybin's effects on cognitive functioning and longer-term emotional and social cognition outcomes. Rucker and colleagues set out to evaluate the safety, feasibility and cognitive and emotional effects of single oral doses of psilocybin (10 mg and 25 mg) compared with placebo in healthy volunteers. The study additionally explored a model of simultaneous administration — dosing up to six participants at once with individual psychological support — as a potentially more time- and cost-efficient approach to delivering therapy. The authors aimed to measure short- and longer-term changes in cognitive domains using the CANTAB battery and in emotional/social processing with multiple standardised tests, while systematically capturing adverse events over a 12-week follow-up.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Rucker, J. J., Marwood, L., Ajantaival, R. J., Bird, C., Eriksson, H., Harrison, J., Lennard-Jones, M., Mistry, S., Saldarini, F., Stansfield, S., Tai, S. J., Williams, S., Weston, N., Malievskaia, E., & Young, A. H. (2022). The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation. Journal of Psychopharmacology, 36(1), 114-125. https://doi.org/10.1177/02698811211064720
References (26)
Papers cited by this study that are also in Blossom
Anderson, B. T., Danforth, A. L., Daroff, R. et al. · EClinicalMedicine (2020)
Bernasconi, F. ;., Schmidt, A. ;., Pokorny, T. ;. et al. · Cerebral Cortex (2013)
Carhart-Harris, R. L., Goodwin, G. M. · Neuropsychopharmacology (2017)
Carhart-Harris, R. L., Bolstridge, &. M., Day, C. M. J. et al. · Psychopharmacology (2017)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Dos Santos, R. G., Hallak, J. E., Bouso, J. C. · Therapeutic Advances in Psychopharmacology (2017)
Gabay, A. S., Carhart-Harris, R. L., Mazibuko, N. et al. · Scientific Reports (2018)
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Halberstadt, A. L., Geyer, M. A. · Neuropharmacology (2011)
Show all 26 referencesShow fewer
Harman, W. W., McKim, R. H., Mogar, R. E. et al. · Psychological Reports (1966)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Kometer, M., Schmidt, A., Bachmann, R. et al. · Biological Psychiatry (2012)
Leary, T., Litwin, G. H., Metzner, R. · Journal of Nervous and Mental Disease (1977)
Litjens, R. P. W., Brunt, T. M., Alderliefste, G. et al. · European Neuropsychopharmacology (2014)
Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (2019)
Mason, N. L., Mischler, E., Uthaug, M. V. et al. · Journal of Psychoactive Drugs (2019)
Moreno, F. A., Wiegand, C. B., Taitano, E. K. et al. · Journal of Clinical Psychiatry (2006)
Passie, T., Seifert, J., Schneider, U. et al. · Addiction Biology (2002)
Pokorny, T., Preller, K. H., Kometer, M. et al. · International Journal of Neuropsychopharmacology (2017)
Preller, K. H., Pokorny, D., Hock, A. et al. · PNAS (2016)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Rucker, J., Young, A. H., Jelen, L. A. et al. · Journal of Psychopharmacology (2016)
Nielson, E. M., Tai, S. J., Lennard-Jones, M. et al. · Frontiers in Psychiatry (2021)
Vollenweider, F. X., Csomor, P. A., Knappe, B. et al. · Neuropsychopharmacology (2007)
Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)
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