Substance Use Disorders (SUD)Psilocybin

Dose-response relationships of psilocybin-induced subjective experiences in humans

This meta-analysis of controlled studies using standard questionnaires found a positive dose–response between oral psilocybin and most subjective effects—particularly perceptual alterations and positively experienced ego dissolution—whereas challenging experiences showed little dose dependence. The findings, derived from pooled laboratory data, provide reference dose–response estimates for experimental and clinical research but may not generalise to recreational settings.

Authors

  • Hirschfeld, T.
  • Schmidt, T. T.

Published

Journal of Psychopharmacology
meta Study

Abstract

Background

Psilocybin is the psychoactive component in Psilocybe mushrooms (‘magic mushrooms’). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies.

Aim

Establishing dose–response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups.

Method

We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose–response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale.

Results

Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose.

Conclusion

Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences.

Available with Blossom Pro

Research Summary of 'Dose-response relationships of psilocybin-induced subjective experiences in humans'

Introduction

Psilocybin, the primary psychoactive component of Psilocybe mushrooms, produces altered states of consciousness (ASC) through agonism at 5-HT2A receptors. Previous research has linked the phenomenological quality of psilocybin-induced experiences — including mystical-type experiences and ego-dissolution — to positive changes in mood and therapeutic outcomes in several clinical contexts. Despite growing interest in whether the subjective experience itself mediates therapeutic benefits, no meta-analysis had quantified how subjective effects scale with psilocybin dose across studies using standardised psychometric instruments. Hirschfeld and Schmidt set out to estimate dose-response relationships for psilocybin-induced subjective experiences measured with validated questionnaires in controlled, oral-administration studies. The primary aim was to derive linear dose-response estimates across multiple psychometric scales using the Altered States Database (ASDB) and a meta-regression approach suited to dependent effect sizes; a secondary aim was to explore whether including available patient data changed those dose-response patterns. The authors frame these estimates as a reference for experimental and clinical dose selection while noting non-pharmacological influences on subjective effects.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

See Pro PlansAlready have an account? Sign in

Full Text PDF

Full Paper PDF

Create a free account to open full-text PDFs.

Create Free AccountAlready have an account? Sign in

Study Details

References (48)

Papers cited by this study that are also in Blossom

Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)

Neuroticism is associated with challenging experiences with psilocybin mushrooms

Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Personality and Individual Differences (2017)

78 cited
Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study

Barsuglia, J. P., Davis, A. K., Palmer, R. et al. · Frontiers in Psychology (2018)

Spatiotemporal Brain Dynamics of Emotional Face Processing Modulations Induced by the Serotonin 1A/2A Receptor Agonist Psilocybin

Bernasconi, F. ;., Schmidt, A. ;., Pokorny, T. ;. et al. · Cerebral Cortex (2013)

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults

Brown, R. T., Nicholas, C. R., Cozzi, N. V. et al. · Clinical Pharmacokinetics (2017)

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences

Carbonaro, T. M., Hurwitz, E., Johnson, M. W. · Psychopharmacology (2017)

102 cited
The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability

Carhart-Harris, R. L., Williams, T. M., Sessa, B. et al. · Journal of Psychopharmacology (2010)

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

Carhart-Harris, R. L., Bolstridge, &. M., Day, C. M. J. et al. · Psychopharmacology (2017)

Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

Carter, O., Burr, D. C., Pettigrew, J. D. et al. · Journal of Cognitive Neuroscience (2006)

Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans

Carter, O. L., Hasler, F. ;., Pettigrew, J. D. et al. · Psychopharmacology (2007)

Show all 48 references
Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers

Gouzoulis-Mayfrank, E., Heekeren, K., Neukirch, A. et al. · Pharmacopsychiatry (2005)

187 cited
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)

Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later

Griffiths, R. R. · Journal of Psychopharmacology (2008)

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer

Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)

Predicting responses to psychedelics: a prospective study

Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)

339 cited
Constructing drug effects: a history of set and setting

Hartogsohn, I. · Drug Science Policy and Law (2017)

389 cited
Human hallucinogen research: guidelines for safety

Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)

Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)

Long-term follow-up of psilocybin-facilitated smoking cessation

Johnson, M. W., Garcia-Romeu, A., Griffiths, R. R. · The American Journal of Drug and Alcohol Abuse (2016)

562 cited
Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors

Kometer, M., Schmidt, A., Bachmann, R. et al. · Biological Psychiatry (2012)

Reactions to psilocybin administered in a supportive environment

Leary, T., Litwin, G. H., Metzner, R. · Journal of Nervous and Mental Disease (1977)

Rostral Anterior Cingulate Thickness Predicts the Emotional Psilocybin Experience

Lewis, C. R., Preller, K. H., Braden, B. B. et al. · Biomedicines (2020)

24 cited
Modern clinical research on LSD

Liechti, M. E. · Neuropsychopharmacology (2017)

Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness

Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)

Factor analysis of the mystical experience questionnaire: A study of experiences occasioned by the hallucinogen psilocybin

MacLean, K. A., Leoutsakos, J. S., Johnson, M. W. et al. · Journal for the Scientific Study of Religion (2012)

350 cited
A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding

Madsen, M. K., Fisher, P. M., Stenbæk, D. S. et al. · European Neuropsychopharmacology (2020)

Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences

Majic, T., Schmidt, T. T., Gallinat, J. · Journal of Clinical Psychopharmacology (2015)

High dose psilocybin is associated with positive subjective effects in healthy volunteers

Nicholas, C. R., Henriquez, K. M., Gassman, M. C. et al. · Journal of Psychopharmacology (2018)

61 cited
Effects of Schedule I drug laws on neuroscience research and treatment innovation

King, C., Nichols, D. E. · Nature Reviews Neuroscience (2013)

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience

Pokorny, T., Preller, K. H., Kraehenmann, R. et al. · European Neuropsychopharmacology (2016)

103 cited
Effect of psilocybin on empathy and moral decision-making

Pokorny, T., Preller, K. H., Kometer, M. et al. · International Journal of Neuropsychopharmacology (2017)

155 cited
Effects of serotonin 2A/1A receptor stimulation on social exclusion processing

Preller, K. H., Pokorny, D., Hock, A. et al. · PNAS (2016)

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Quednow, B. B., Kometer, M., Geyer, M. A. et al. · Neuropsychopharmacology (2011)

Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial

Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)

Replication and extension of a model predicting response to psilocybin

Russ, S. L., Carhart-Harris, R. L., Maruyama, G. et al. · Psychopharmacology (2019)

55 cited
States and traits related to the quality and consequences of psychedelic experiences

Russ, S. L., Carhart-Harris, R. L., Maruyama, G. et al. · Psychology of Consciousness Theory Research and Practice (2019)

The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions

Schmidt, A., Kometer, M., Bachmann, R. et al. · Psychopharmacology (2012)

P300-mediated modulations in self-other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self-other overlap

Smigielski, L., Kometer, M., Scheidegger, M. et al. · Human Brain Mapping (2020)

2 cited
Psychometric evaluation of the altered states of consciousness rating scale (OAV)

Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)

Prediction of psilocybin response in healthy volunteers

Studerus, E., Gamma, A., Kometer, M. et al. · PLOS ONE (2012)

Psilocybin - Summary of knowledge and new perspectives

Tylš, F., Páleníček, T., Horacek, J. · European Neuropsychopharmacology (2013)

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

Uthaug, M. V., Lancelotta, R., Szabo, A. et al. · Psychopharmacology (2019)

86 cited
The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)

Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

Vollenweider, F. X., Preller, K. H. · Nature Reviews Neuroscience (2020)

Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action

Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)

The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval

Vollenweider, F. X., Csomor, P. A., Knappe, B. et al. · Neuropsychopharmacology (2007)

Effects of psilocybin on time perception and temporal control of behaviour in humans

Wittmann, M., Carter, O., Hasler, F. et al. · Journal of Psychopharmacology (2007)

212 cited

Cited By (22)

Papers in Blossom that reference this study

The Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience: A Retrospective Analysis

Kirlić, N., Atli, M., Mistry, S. et al. · Journal of Clinical Psychopharmacology (2025)

Exploring the Therapeutic Effects of Psychedelics Administered to Military Veterans in Naturalistic Retreat Settings

Calnan, M., Blest-Hopley, G., Busch, C. et al. · Brain and Behavior (2025)

Insights on Psychedelics: A Systematic Review of Therapeutic Effects

Kugel, J., Laukkonen, R., Yaden, D. B. et al. · Neuroscience and Biobehavioral Reviews (2025)

Psychedelics Align Brain Activity with Context

Stoliker, D., Novelli, L., Khajehnejad, M. et al. · Biorxiv (2025)

The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression

Goodwin, G. M., Aaronson, S. T., Alvarez, O. et al. · Journal of Affective Disorders (2025)

28 cited
Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies

Sabé, M., Sulstarova, A., Glangetas, A. et al. · Molecular Psychiatry (2024)

Enhanced visual contrast suppression during peak psilocybin effects: Psychophysical results from a pilot randomized controlled trial

Swanson, L. R., Jungers, S., Varghese, R. et al. · Journal of Vision (2024)

Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants

Vizeli, P., Studerus, E., Holze, F. et al. · Translational Psychiatry (2024)

Psilocybin for Opioid Use Disorder in Two Adults Stabilized on Buprenorphine: A Technical Report on Study Modifications and Preliminary Findings

Nicholas, C. R., Horton, D. M., Malicki, J. et al. · Psychedelic Medicine (2023)

Psilocybin-assisted therapy for depression: A systematic review and meta-analysis

Haikazian, S., Chen-Li, D., Johnson, D. et al. · Psychiatry Research (2023)

Show all 22 papers
Psilocybin-assisted therapy for depression: A systematic review and dose-response meta-analysis of human studies

Pereira, L. · European Neuropsychopharmacology (2023)

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication

Goodwin, G. M., Croal, M., Feifel, D. et al. · Neuropharmacology (2023)

Dose-response relationships of LSD-induced subjective experiences in humans

Prugger, J., Hirschfeld, T., Majic, T. et al. · Neuropsychopharmacology (2023)

19 cited
Optimizing outcomes in psilocybin therapy: Considerations in participant evaluation and preparation

Modlin, N. L., Miller, T. M., Rucker, J. J. et al. · Journal of Affective Disorders (2023)

The Altered States Database: Psychometric data from a systematic literature review

Prugger, J., Derdiyok, E., Dinkelacker, J. et al. · Scientific Data (2022)

Predictors and potentiators of psychedelic-occasioned mystical experiences

Gandy, S. · Journal of Psychedelic Studies (2022)

Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report

McCulloch, D. E-W., Madsen, M. K., Jensen, P. S. et al. · Frontiers in Pharmacology (2022)

79 cited
Classic Psychedelic Drugs: Update on Biological Mechanisms

Vollenweider, F. X., Smallridge, J. W. · Pharmacopsychiatry (2022)

71 cited
Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)

Bridging the Gap? Altered Thalamocortical Connectivity in Psychotic and Psychedelic States

Avram, M., Rogg, H., Korda, A. et al. · Frontiers in Psychiatry (2021)

35 cited
Safety pharmacology of acute LSD administration in healthy subjects

Holze, F., Caluori, T. V., Vizeli, P. et al. · Psychopharmacology (2021)

Safer Tripping: Serotonergic Psychedelics and Drug Checking. Submission and Detection Rates, Potential Harms, and Challenges for Drug Analysis

Hirschfeld, T., Smit-Rigter, L., Van Der Gouwe, D. et al. · Current Addiction Reports (2021)

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.

See Pro PlansSign in
Dose-response relationships of psilocybin-induced... — Research Summary & Context | Blossom