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

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.

Keywords: Phenomenology; dose–response relationship; meta-regression; psilocybin; subjective experience.

Figure 1.

Dose–response relationships for the Altered States of Consciousness Rating Scale. (a) Dose-specific subjective effects of psilocybin measured with the Altered States of Consciousness Rating Scale. The data of this instrument can be analysed according to a schema where items are organized into five factors, called ‘dimensions’ of ASC experiences (5D-ASC). (b) A finer-grained quantification of specific aspects of subjective experiences is obtained when the questionnaire is analysed according to the 11-factors schema. These 11 factors can be considered subscales of the three core dimensions of the 5D-ASC, namely Oceanic Boundlessness, Dread of Ego Dissolution and Visionary Restructuralization (see corresponding colours of the subscale names). Doses are given in microgram per kilogram body weight; effects are given as the percentage score of the maximum score on each factor (questionnaire items are anchored by 0% for ‘No, not more than usual’ and 100% for ‘Yes, much more than usual’). Circle colour indicates data from the same sample of participants (the same colour corresponds to statistically dependent data), while circle size represents the weight of the data based on study variance (see Methods). Spiderplots present the estimated dose–responses for 100–300 μg/kg body weight on the 5D-ASC and 100–400 μg/kg body weight on the 11 subscales, corresponding to the range of doses that were included in the respective analyses. The colour of individual scales corresponds to the primary dimensions and the respective subscales.

Figure 2.

Dose–response relationships for MEQ30 and HRS. Dose-specific subjective effects of psilocybin for the psychometric instruments (a) MEQ30 and (b) HRS. Doses are given as microgram per kilogram body weight. Effects on the MEQ30 are presented as the percentage score of the maximum score. Effects on the HRS range from 0 to 4 (items in the questionnaire from 0 ‘Not at all’ to 4 ‘Extreme’). Circle colour indicates data from the same sample of participants (the same colour corresponds to statistically dependent data), circle size represents the weight of the data based on study variance (see Methods). Spiderplots present the estimated dose–responses for 100–600 μg/kg body weight on the MEQ30 and 100–400 μg/kg body weight on the HRS, corresponding to the range of doses that were included in the respective analyses.