Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches
Post hoc analyses of 10 studies (N=288) administering 20–30 mg/70 kg psilocybin found no relationship between body weight (49–113 kg) or sex and acute subjective effects (mystical, challenging, intensity) under weight‑adjusted or approximated fixed (≈25 mg) dosing. These findings suggest fixed‑dose administration produces comparable subjective effects across weights and, given its greater convenience and lower cost, is preferable to weight‑adjusted dosing.
Authors
- Albert Garcia-Romeu
- Roland Griffiths
- Matthew Johnson
Published
Abstract
Background
Growing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe and promising pharmacotherapy for treatment of mood and substance use disorders when administered as part of a structured intervention. In most trials to date, psilocybin dose has been administered on a weight-adjusted basis rather than the more convenient procedure of administering a fixed dose.
Aims
The present post hoc analyses sought to determine whether the subjective effects of psilocybin are affected by body weight when psilocybin is administered on a weight-adjusted basis and when psilocybin is administered as a fixed dose.
Methods
We analyzed acute subjective drug effects (mystical, challenging, and intensity) associated with therapeutic outcomes from ten previous studies (total N = 288) in which psilocybin was administered in the range 20 to 30 mg/70 kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20 mg/70 kg ( n = 120), participants receiving 30 mg/70 kg ( n = 182), and participants whose weight-adjusted dose was about 25 mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) ( n = 103).
Results
In the 20 mg/70 kg and 30 mg/70 kg weight-adjusted groups, and in the fixed dose group, no significant associations were found between subjective effects and demographic variables including body weight or sex. Across a wide range of body weights (49 to 113 kg) the present results showed no evidence that body weight affected subjective effects of psilocybin.
Conclusions
These results suggest that the convenience and lower cost of administering psilocybin as a fixed dose outweigh any potential advantage of weight-adjusted dosing.
Research Summary of 'Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches'
Introduction
Interest in classic psychedelics has increased because these compounds, which act primarily as serotonin 2A receptor (5-HT2A R) agonists, show therapeutic promise for mood and substance use disorders. Psilocybin, a prodrug converted to psilocin, has produced moderate-to-large effect sizes in trials combined with supportive counselling and has yielded persistent benefits after one to a few administrations. Most clinical studies to date have used body weight-adjusted dosing (for example 30 mg/70 kg), but a fixed-dose approach would be operationally simpler and less costly; it remains uncertain whether weight-adjustment is necessary to achieve comparable subjective or therapeutic effects across people of differing body mass. Garcia-Romeu and colleagues set out to examine whether acute subjective effects of psilocybin vary as a function of body weight under both weight-adjusted and fixed-dose scenarios. Using pooled post hoc data from ten prior studies, the investigators focused on three specific questions: whether subjective effects vary with body weight at 20 mg/70 kg, at 30 mg/70 kg, and when participants received an absolute dose of about 25 mg (to approximate a fixed dosing regimen being used in registration trials). The analysis concentrates on acute subjective measures (mystical-type experiences, challenging experiences, and peak intensity) because these effects have been linked in prior work to subsequent therapeutic outcomes.
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
Garcia-Romeu, A., Barrett, F. S., Carbonaro, T. M., Johnson, M. W., & Griffiths, R. R. (2021). Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches. Journal of Psychopharmacology, 35(4), 353-361. https://doi.org/10.1177/0269881121991822
References (26)
Papers cited by this study that are also in Blossom
Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)
Barrett, F. S., Carbonaro, T. M., Hurwitz, E. et al. · Psychopharmacology (2018)
Barrett, F. S., Doss, M. K., Sepeda, N. D. et al. · Scientific Reports (2020)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Personality and Individual Differences (2017)
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)
Carbonaro, T. M., Hurwitz, E., Johnson, M. W. · Psychopharmacology (2017)
Carhart-Harris, R. L., Bolstridge, &. M., Day, C. M. J. et al. · Psychopharmacology (2017)
Carhart-Harris, R. L., Roseman, L., Bolstridge, M. et al. · Scientific Reports (2017)
Show all 26 referencesShow fewer
Davis, A. K., Barrett, F. S., May, D. G. et al. · JAMA Psychiatry (2021)
Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W. · Current Drug Abuse Reviews (2015)
Goldberg, S. B., Pace, B. T., Nicholas, C. R. et al. · Psychiatry Research (2020)
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)
Hartogsohn, I. · Journal of Psychopharmacology (2016)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Johnson, M. W., Garcia-Romeu, A., Griffiths, R. R. · The American Journal of Drug and Alcohol Abuse (2016)
Liechti, M. E., Gamma, A., Vollenweider, F. X. · Psychopharmacology (2001)
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)
Madsen, M. K., Fisher, P. M., Stenbæk, D. S. et al. · European Neuropsychopharmacology (2020)
Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Studerus, E., Gamma, A., Kometer, M. et al. · PLOS ONE (2012)
Cited By (28)
Papers in Blossom that reference this study
Henningfield, J. E., Barrett, F. S., Evans, S. M. et al. · Journal of Psychopharmacology (2026)
Garcia-Romeu, A., Naudé, G. P., Rebman, A. W. et al. · Scientific Reports (2026)
Knock, E., Siefried, K. J., Gill Bedi, |. et al. · Addiction (2025)
Aday, J. S., Mcafee, J., Conroy, D. A. et al. · Frontiers in Pain Research (2025)
Stoliker, D., Novelli, L., Khajehnejad, M. et al. · Biorxiv (2025)
Syed, O. A., Petranker, R., Fewster, E. C. et al. · Journal of Psychoactive Drugs (2024)
Stroud, J., Rice, C., Orsini, A. et al. · Psychopharmacology (2024)
Card, K. G., Grewal, A., Closson, K. et al. · Journal of Psychoactive Drugs (2023)
Nayak, S., Jackson, H., Sepeda, N. D. et al. · Frontiers in Psychiatry (2023)
Mallaroni, P., Mason, N. L., Reckweg, J. T. et al. · Clinical Pharmacology and Therapeutics (2023)
Show all 28 papersShow fewer
Thal, S. B., Wieberneit, M., Sharbanee, J. M. et al. · Journal of Humanistic Psychology (2023)
van der Meer, P. B., Fuentes, J. J., Kaptein, A. A. et al. · Frontiers in Psychiatry (2023)
Holze, F., Becker, A. M., Kolaczynska, K. E. et al. · Clinical Pharmacology and Therapeutics (2022)
MacCallum, C. A., Pistawka, C. A., Deol, J. K. et al. · Frontiers in Psychiatry (2022)
Giribaldi, B., Lyons, T., Rosas, F. E. et al. · Journal of Psychopharmacology (2022)
Stoliker, D., Egan, G. F., Friston, K. J. et al. · Pharmacological Reviews (2022)
Cavanna, F., Muller, S., de la Fuente, L. A. et al. · Translational Psychiatry (2022)
McCulloch, D. E-W., Knudsen, G. M., Barrett, F. S. et al. · Neuroscience and Biobehavioral Reviews (2022)
Good, M., Joel, Z., Benway, T. et al. · European Journal of Pharmacology (2022)
Wießner, I., Olivieri, R., Falchi, M. et al. · European Neuropsychopharmacology (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)
Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)
Cavanna, F., Muller, S., de la Fuente, L. A. et al. · Translational Psychiatry (2021)
Becker, A. M., Holze, F., Grandinett, T. et al. · Clinical Pharmacology and Therapeutics (2021)
Mason, N. L., Feilding, A., Ramaekers, J. G. · European Neuropsychopharmacology (2020)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.