Anxiety DisordersHealthy VolunteersNeuroimaging & Brain MeasuresPsilocybin

Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals

In healthy volunteers, a medium–high dose of psilocybin produced a significant increase in trait mindfulness at three months that correlated positively with the intensity of the acute mystical-type experience. Higher baseline trait mindfulness was also associated with lower 5‑HT2A receptor binding in the right amygdala.

Authors

  • Gitte Knudsen
  • Patrick Fisher
  • Dea Stenbæk

Published

Frontiers in Psychology
individual Study

Abstract

Background

Psilocybin-induced mystical-type experiences are associated with lasting positive psychological outcomes. Recent studies indicate that trait mindfulness is increased 3 months after psilocybin intake, preceded by decreases in neocortical serotonin 2A receptor (5-HT2AR) binding. However, the association between psilocybin-induced mystical-type experiences and subsequent changes in trait mindfulness remains unexplored, as does the association between pre-drug trait mindfulness and 5-HT2AR binding in the healthy brain.

Aim

We evaluated whether psilocybin induced lasting increases in trait mindfulness in healthy volunteers, and whether the mystical-type experience was associated with this increase. We further examined the association between pre-drug trait mindfulness and 5-HT2AR binding in neocortex and selected frontolimbic regions.Materials and methodsForty-six medium-high dose psilocybin sessions were conducted in 39 healthy individuals. The mystical-type experience was measured with the Mystical Experience Questionnaire (MEQ) at the end of the session. Trait mindfulness was measured using the Mindful Attention and Awareness Scale (MAAS) at baseline and 3 months after the psilocybin session. Thirty-two of the participants completed pre-drug [11C]-Cimbi-36 positron emission tomography (PET) to assess 5-HT2AR binding in neocortex and, post-hoc, in the frontolimbic regions amygdala, frontal cortex, and anterior cingulate cortex.

Results

The MAAS score was significantly increased at 3-month follow-up (p = 3.24 × 10–6), a change positively associated with the MEQ score (p = 0.035). Although the association between pre-drug MAAS score and neocortex 5-HT2AR binding was not significant (p = 0.24), post-hoc analyses revealed a significant negative association between MAAS and right amygdala 5-HT2AR binding (pFWER = 0.008).

Conclusion

We here show that lasting changes in trait mindfulness following psilocybin administration are positively associated with intensity of the mystical-type experience, suggesting that the acute phenomenology of psilocybin facilitates a shift in awareness conducive for mindful living. We furthermore show that higher pre-drug trait mindfulness is associated with reduced 5-HT2AR binding in the right amygdala.

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Research Summary of 'Lasting increases in trait mindfulness after psilocybin correlate positively with the mystical-type experience in healthy individuals'

Introduction

Psilocybin, a tryptamine alkaloid found in Psilocybe mushrooms, has shown promise as a therapeutic agent across several psychiatric conditions and is known to produce an altered state of consciousness that can include a mystical-type experience. Previous small studies have reported increases in trait mindfulness after psilocybin administration, and other psychedelics and meditation-linked interventions have produced similar short- and medium-term increases in mindfulness-related measures. Given that trait mindfulness correlates with indices of psychological health and that 5-HT2A receptor (5-HT2A R) signalling is central to psilocybin’s effects, the relationships among psilocybin-induced mystical experiences, changes in trait mindfulness, and pre-drug 5-HT2A R binding in the healthy brain remain of interest. Conceicao and colleagues set out to test three related hypotheses in healthy volunteers: (1) that trait mindfulness increases from baseline to 3 months after a medium-to-high dose psilocybin session, (2) that the intensity of the psilocybin-induced mystical-type experience is positively associated with any such increase in trait mindfulness, and (3) that baseline (pre-drug) 5-HT2A R binding in neocortex and selected frontolimbic regions is negatively associated with trait mindfulness. The study therefore combines self-report measures taken before and after psilocybin with pre-drug PET imaging in a subset of participants to explore behavioural and neurochemical correlates of mindfulness-related change.

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