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

This pooled analysis (n=77) of body mass index (BMI) data from three psilocybin (25mg) trials finds that BMI doesn’t predict the intensity of the response to psilocybin. A fixed-dosing schedule (instead of dosage based on weight which is common for MDMA and ketamine) is probably best going forward in psilocybin-assisted trials.

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.“

Authors: Meg J. Spriggs, Bruna Giribaldi, Taylor Lyons, Fernando E. Rosas, Laura S. Kärtner, Tobias Buchborn, Hannah M. Douglass, Leor Roseman, Christopher Timmermann, David Erritzoe, David J. Nutt & Robin L. Carhart-Harris

Summary of BMI doesn’t predict responses to psilocybin

Psilocybin-assisted therapy is making a resurgence in psychiatry, with greater plasma psilocin and 5-HT2A receptor occupancy being associated with a greater intensity of subjective effects. However, there is currently no data on how the relationship between 5-HT2A receptor expression and acute experience translates into long-term outcomes.

5-HT2A receptor density in the brain varies across individuals based on clinical and demographic factors, including body mass index (BMI). A high-fat diet is associated with a greater density of 5-HT2A receptors in the brain, while a reduction in 5-HT2A receptor density has been demonstrated in patients with eating disorders.