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

This meta-analysis (n=349) found that the dose of psilocybin (3-27mg/70kg) correlated positively with positive changes in perception (e.g. ego dissolution). Negative experiences were barely modulated by dose.

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.”

Authors: Tim Hirschfeld & Timo T. Schmidt

Notes

This paper looked at (almost exclusively) double-blind placebo-controlled studies with healthy populations. The data came from the excellent Altered States Database (ASBD).

Another analysis of 288 participants with mental health disorders by Garcia-Romeu and colleagues (2021) argued for a fixed-dosing (25mg psilocybin) schedule (instead of basing it on bodyweight) which runs somewhat counter to the findings from this study. But both were in very different populations and looking here at the total dosage and there dosage x bodyweight.

The responses to three questionnaires were analyzed, the Altered States of Consciousness Rating Scale (5D-ASC), Mystical Experience Questionnaire (MEQ-30), and Hallucinogen Rating Scale (HRS).

“In summary, psilocybin mainly induced dose-dependent alterations in perception and positively experienced ego dissolution. Subjective experiences for high doses of psilocybin are characterized by all aspects of mystical-type experiences captured by the MEQ30 questionnaire. The given data did not support the premise that higher doses of psilocybin would directly induce the more aversive aspects of experiences; however, as the given data are average scores, it cannot be excluded that some individuals undergo highly challenging experiences.“

As mentioned in the abstract, the findings here apply to a clinical/university setting and many other factors around set and setting will also greatly impact someone’s subjective experience when taking a dose of psilocybin.

In the discussion of the paper, many comparisons are made to other studies. These include other types of administration (iv, similar results), patient populations (somewhat larger effect possibly due to set and setting), other psychedelics (LSD, comparable but more Audio-visual Synaesthesia and Changed Meaning of Percepts).