Healthy VolunteersNeuroimaging & Brain MeasuresPsilocybin

Psilocybin-induced changes in cerebral blood flow are associated with acute and baseline inter-individual differences

In healthy volunteers, oral psilocybin produced dose-dependent changes in cerebral blood flow (relative and absolute) that correlated with the intensity of the acute subjective psychedelic experience and with baseline psychological and neurobiological characteristics, revealing marked inter-individual heterogeneity in neural response. These associations point to candidate biomarkers linking baseline traits to psilocybin-induced brain changes and support a personalised medicine approach for psychedelic-assisted therapy.

Authors

  • Franz Vollenweider
  • Katrin Preller
  • Nathalie Rieser

Published

Scientific Reports
individual Study

Abstract

Research into the use of psilocybin for the treatment of psychiatric disorders is a growing field. Nevertheless, robust brain–behavior relationships linking psilocybin-induced brain changes to subjective drug-induced effects have not been established. Furthermore, it is unclear if the acute neural effects are dependent on individual heterogeneity in baseline characteristics. To address this, we assessed the effects of three oral doses of psilocybin vs. placebo on cerebral blood flow (CBF) using arterial spin labeling in healthy participants (N = 70; n = 31, 0.16 mg/kg; n = 10, 0.2 mg/kg; n = 29, 0.215 mg/kg). First, we quantified psilocybin-induced changes in relative and absolute CBF. Second, in an exploratory analysis, we assessed whether individual baseline characteristics and subjective psychedelic experience are associated with changes in CBF. Psychological and neurobiological baseline characteristics correlated with the psilocybin-induced reduction in relative CBF and the psilocybin-induced subjective experience. Furthermore, the psilocybin-induced subjective experience was associated with acute changes in relative and absolute CBF. The results demonstrated that inter-individual heterogeneity in the neural response to psilocybin is associated with baseline characteristics and shed light on the mechanisms underlying the psychedelic-induced altered state. Overall, these findings help guide the search for biomarkers, paving the way for a personalized medicine approach within the framework of psychedelic-assisted therapy.

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Research Summary of 'Psilocybin-induced changes in cerebral blood flow are associated with acute and baseline inter-individual differences'

Introduction

Classic psychedelic psilocybin acts primarily as a serotonin 5-HT2A/1A receptor agonist and produces a range of altered conscious states including visual phenomena, synesthesia, feelings of unity, and insightfulness. Prior neuroimaging work has reported widespread acute effects of psychedelics on brain activity and connectivity — for example increased global functional connectivity in sensory areas and altered regional metabolism — but clear, robust brain–behaviour relationships linking psilocybin-induced neural changes to the subjectively reported psychedelic experience remain unresolved. It is also uncertain whether acute neural responses to psilocybin depend on inter-individual baseline characteristics. Rieser and colleagues set out to address these gaps by assessing how oral psilocybin affects cerebral blood flow (CBF) and by testing whether individual baseline neurobiological and psychological measures relate to acute CBF changes and to the subjective psychedelic experience. Using arterial spin labelling (ASL) perfusion MRI in healthy participants, the study aimed to quantify both relative CBF (rCBF), which normalises voxel-wise perfusion to global gray matter perfusion, and absolute CBF (aCBF), and to explore correlations between these imaging measures, baseline psychological traits, and acute subjective effects measured with a standard altered-states questionnaire.

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References (34)

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