Trial PaperEating DisordersPsilocybin

Body mass index (BMI) does not predict responses to psilocybin

Pooled analysis of three therapeutic trials using a fixed 25 mg psilocybin dose found that BMI did not predict acute psychedelic intensity, mystical experiences, perceptual changes, emotional breakthroughs, or two‑week improvements in well‑being, with Bayesian evidence supporting the null. These results support the use of a standardised fixed therapeutic dose rather than routine weight‑adjusted dosing.

Authors

  • Fernando Rosas
  • Robin Carhart-Harris
  • David Nutt

Published

Journal of Psychopharmacology
individual Study

Abstract

Background

Psilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.

Method

Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.

Results

Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.

Conclusions

These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.

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Research Summary of 'Body mass index (BMI) does not predict responses to psilocybin'

Introduction

Spriggs and colleagues frame their study around inter-individual differences in 5-HT2A receptor density and how these may relate to body mass index (BMI). Prior work has reported positive correlations between BMI and 5-HT2A binding in several cortical regions, genetic links between 5-HT2A polymorphisms and body mass, and altered receptor density in disorders such as anorexia nervosa. Body weight-adjusted dosing has been common in psilocybin research because weight is a conventional pharmacological covariate, but body composition and receptor-level differences raise uncertainty about whether weight-adjusted dosing is necessary or optimal for producing consistent acute and long-term psychological effects from psilocybin. To address this gap, the investigators pooled data from three studies at the Centre for Psychedelic Research, Imperial College London, in which a fixed high dose of 25 mg psilocybin was administered in a supportive setting. The analysis aimed to assess whether BMI predicts (1) the intensity and qualitative features of the acute psychedelic experience, indexed by the Altered States of Consciousness (ASC) questionnaire and the Emotional Breakthrough Inventory (EBI), and (2) longer-term changes in well-being indexed by the Warwick–Edinburgh Mental Well-being Scale (WEMWBS). Given limited prior expectations, both frequentist and Bayesian hypothesis testing were used so that evidence for or against the null hypothesis could be quantified.

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Study Details

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