High dose psilocybin is associated with positive subjective effects in healthy volunteers
In a within-subject study of 12 healthy volunteers given three escalating oral psilocybin doses (0.3–0.6 mg/kg), higher doses produced greater Mystical Experience Questionnaire scores—particularly on the transcendence of time and space subscale—and positive persisting effects 30 days later. Pharmacokinetics scaled with dose but did not predict mystical scores, and a complete mystical experience was not necessary for positive outcomes.
Authors
- Christopher Nicholas
- Nicholas Cozzi
- Paul Hutson
Published
Abstract
Aim
The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects.
Methods
Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8–36.6 mg; 27.1–54.0 mg; 36.3–59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire.
Results
There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience.
Conclusions
High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.
Research Summary of 'High dose psilocybin is associated with positive subjective effects in healthy volunteers'
Introduction
Psilocybin is a classical psychedelic compound reported to produce intense alterations in perception, mood and sense of self, and in some people to occasion a so-called mystical or spiritual experience characterised by unity, sacredness, ineffability and transcendence of time and space. Early clinical and experimental work suggests that psilocybin can produce lasting positive psychological effects and improvements in mood and substance use outcomes when administered in supportive settings. Most contemporary human studies, however, have used a relatively narrow dose range (about 20–30 mg per 70 kg, roughly 0.28–0.43 mg/kg), leaving uncertainty about subjective and persisting effects at higher doses and whether a full mystical experience is necessary for beneficial outcomes. Nicholas and colleagues set out to examine the relationship between escalating, higher oral doses of psilocybin and acute and persisting positive subjective effects in healthy volunteers. The primary aim reported here was to relate dose and pharmacokinetic measures to scores on the Mystical Experience Questionnaire (MEQ30) and on the Persisting Effects Questionnaire (PEQ) collected up to 30 days after the last dose; the data derive from an open-label Phase I study that also characterised pharmacokinetics and safety of weight‑based dose escalation up to 0.60 mg/kg.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Create a free account to open full-text PDFs.
Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Nicholas, C. R., Henriquez, K. M., Gassman, M. C., Cooper, K. M., Muller, D., Hetzel, S., Brown, R. T., Cozzi, N. V., Thomas, C., & Hutson, P. R. (2018). High dose psilocybin is associated with positive subjective effects in healthy volunteers. Journal of Psychopharmacology, 32(7), 770-778. https://doi.org/10.1177/0269881118780713
References (21)
Papers cited by this study that are also in Blossom
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)
Brown, R. T., Nicholas, C. R., Cozzi, N. V. et al. · Clinical Pharmacokinetics (2017)
Carbonaro, T. M., Bradstreet, M. P., Barrett, F. S. et al. · Journal of Psychopharmacology (2016)
Doblin, R. · Journal of Transpersonal Psychology (1991)
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)
Show all 21 referencesShow fewer
Leary, T., Litwin, G. H., Metzner, R. · Journal of Nervous and Mental Disease (1977)
Liechti, M. E. · Neuropsychopharmacology (2017)
Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)
Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)
MacLean, K. A., Leoutsakos, J. S., Johnson, M. W. et al. · Journal for the Scientific Study of Religion (2012)
Richards, W. A., Rhead, J. C., Dileo, F. B. et al. · Journal of Psychedelic Drugs (1997)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Schmid, Y., Enzler, F., Gasser, P. et al. · Biological Psychiatry (2015)
Schmid, Y., Liechti, M. E. · Psychopharmacology (2017)
Studerus, E., Gamma, A., Kometer, M. et al. · PLOS ONE (2012)
Studerus, E., Kometer, M., Hasler, F. et al. · Journal of Psychopharmacology (2010)
Cited By (30)
Papers in Blossom that reference this study
Tylš, F., Páleníček, T., Klučková, T. et al. · Pharmacological Reports (2025)
Nicholas, C. R., Banks, M. I., Lennertz, R. L. et al. · Translational Psychiatry (2024)
Timmermann, C., Zeifman, R. J., Erritzoe, D. et al. · Scientific Reports (2024)
Nicholas, C. R., Horton, D. M., Malicki, J. et al. · Psychedelic Medicine (2023)
Thal, S. B., Wieberneit, M., Sharbanee, J. M. et al. · Journal of Humanistic Psychology (2023)
Kangaslampi, S. · Journal of Psychedelic Studies (2023)
Burmester, D., Madsen, M. K., Szabo, A. et al. · Comprehensive Psychoneuroendocrinology (2023)
MacCallum, C. A., Pistawka, C. A., Deol, J. K. et al. · Frontiers in Psychiatry (2022)
Prugger, J., Derdiyok, E., Dinkelacker, J. et al. · Scientific Data (2022)
Giribaldi, B., Lyons, T., Rosas, F. E. et al. · Journal of Psychopharmacology (2022)
Show all 30 papersShow fewer
Radakovic, C., Radakovic, R., Peryer, G. et al. · Journal of Psychedelic Studies (2022)
Glowacki, D. R., Wonnacott, M. D., Freire, R. et al. · Scientific Reports (2022)
Johnson, S., Letheby, C. · Journal of Psychedelic Studies (2022)
Kopra, E., Ferris, J. A., Winstock, A. R. et al. · Journal of Psychopharmacology (2022)
Gandy, S. · Journal of Psychedelic Studies (2022)
Holze, F., Ley, L., Müller, F. et al. · Neuropsychopharmacology (2022)
Yu, C. L., Liang, C. S., Yang, F. et al. · Journal of Clinical Medicine (2022)
Strickland, J. C., Johnson, M. W. · Advances in Pharmacology (2022)
Strumila, R., Guillaume, S. · Pharmaceuticals (2021)
McGovern, H., Leptourgos, P., Hutchinson, B. et al. · Psyarxiv (2021)
Horton, D. M., Morrison, B., Schmidt, J. · American Journal of Psychotherapy (2021)
Rodan, S., Aouad, P., McGregor, I. S. et al. · OBM Neurobiology (2021)
Bement, W., Banks, M. I., Zahid, Z. et al. · Molecular Biology of the Cell (2021)
Aday, J. S., Davis, A. K., Mitzkovitz, C. M. et al. · ACS Pharmacology and Translational Science (2021)
Hirschfeld, T., Schmidt, T. T. · Journal of Psychopharmacology (2021)
Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)
Goldberg, S. B., Shechet, B., Nicholas, C. R. et al. · Psychological Medicine (2020)
Schmid, Y., Gasser, P., Oehen, P. et al. · Journal of Psychopharmacology (2020)
Aday, J. S., Mitzkovitz, C. M., Bloesch, E. K. et al. · Neuroscience and Biobehavioral Reviews (2020)
Reiff, C. M., Richman, E. E., Nemeroff, C. B. et al. · American Journal of Psychiatry (2020)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.