Depressive DisordersAnxiety DisordersNeuroimaging & Brain MeasuresPersonality & Trait FactorsPsilocybin

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

This open-label study (n=10) found a significant increase in mindfulness (MAAS) and openness (NEO PI-R) after a single high dose (14-21mg) of psilocybin.

Authors

  • Gitte Knudsen
  • Patrick Fisher
  • Dea Stenbæk

Published

European Neuropsychopharmacology
individual Study

Abstract

A single dose of the serotonin 2A receptor (5-HT2AR) agonist psilocybin can have long-lasting beneficial effects on mood, personality, and potentially on mindfulness, but underlying mechanisms are unknown. Here, we for the first time conduct a study that assesses psilocybin effects on cerebral 5-HT2AR binding with [11C]Cimbi-36 positron emission tomography (PET) imaging and on personality and mindfulness. Ten healthy and psychedelic-naïve volunteers underwent PET neuroimaging of 5-HT2AR at baseline (BL) and one week (1W) after a single oral dose of psilocybin (0.2-0.3 mg/kg). Personality (NEO PI-R) and mindfulness (MAAS) questionnaires were completed at BL and at three-months follow-up (3M). Paired t-tests revealed statistically significant increases in personality Openness (p-uncorrected = 0.04, mean change [95%CI]: 4.2[0.4;∞]).

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

Introduction

Psilocybin, the active compound in ‘‘magic mushrooms’’, is a serotonergic psychedelic whose active metabolite psilocin stimulates cortical serotonin 2A receptors (5-HT2AR) and produces a transient altered state of consciousness. Previous clinical and experimental studies have reported that a single dose of psilocybin can yield persistent improvements in mood, reductions in depressive and anxiety symptoms, and long-term increases in the personality trait Openness. Reports and small studies have also suggested that mindfulness-related capacities may increase after psychedelic use, but the durability of such changes and their neurobiological substrates remain unclear. Preclinical work and cross-sectional PET data further suggest that 5-HT2AR agonists can induce receptor internalisation or down-regulation, making changes in cerebral 5-HT2AR levels a plausible molecular mechanism for long-term psychological effects. Korsbak Madsen and colleagues set out to evaluate, in healthy psychedelic-naïve volunteers, whether a single oral dose of psilocybin alters cerebral 5-HT2AR binding and whether any early receptor changes predict longer-term changes in personality and mindfulness. To do so, the investigators obtained [11C]Cimbi-36 PET scans before and one week after psilocybin, and assessed personality and trait mindfulness at baseline and at three months, testing the a priori hypothesis that the trait Openness would increase and exploring associations between receptor-level changes and later psychological outcomes. This approach aims to link molecular neuroimaging with persistent psychological effects following a single psychedelic exposure.

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Study Details

References (27)

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