Neuroimaging & Brain MeasuresPsilocybin

Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow

This double-blind, placebo-controlled study (n=58) investigated the effect of two doses of psilocybin (11mg-15mg/70kg) on cerebral blood flow. The larger dose led to significantly higher ratings on 4 of 11 scales of altered consciousness. It also showed which specific brain regions became more, and less, active.

Authors

  • Franz Vollenweider
  • Katrin Preller
  • Rafael Kraehenmann

Published

NeuroImage
individual Study

Abstract

Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0.160 mg/kg; high dose: 0.215 mg/kg) in two groups of healthy controls (n = 29 in both groups, total N = 58) during rest. We controlled for sex and age and used family-wise error corrected p values in all neuroimaging analyses. Both dose groups reported profound subjective drug effects as measured by the Altered States of Consciousness Rating Scale (5D-ASC) with the high dose inducing significantly larger effects in four out of the 11 scales. After adjusting for global brain perfusion, psilocybin increased relative perfusion in distinct right hemispheric frontal and temporal regions and bilaterally in the anterior insula and decreased perfusion in left hemispheric parietal and temporal cortices and left subcortical regions. Whereas, psilocybin significantly reduced absolute perfusion in frontal, temporal, parietal, and occipital lobes, and bilateral amygdalae, anterior cingulate, insula, striatal regions, and hippocampi. Our analyses demonstrate consistency with both the hyperfrontal hypothesis of psilocybin and the more recent study demonstrating decreased perfusion, depending on analysis method. Importantly, our data illustrate that relative changes in perfusion should be understood and interpreted in relation to absolute signal variations.

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Research Summary of 'Two dose investigation of the 5-HT-agonist psilocybin on relative and global cerebral blood flow'

Introduction

The serotonin (5-HT) system modulates perception, cognition, mood and consciousness, and classic psychedelics such as psilocybin produce profound alterations in these domains. Neuroimaging studies of psilocybin and related 5-HT agonists have reported apparently conflicting results: early PET studies, after correction for global fluctuations, found regional increases in frontal metabolism (a "hyperfrontal" pattern), whereas a more recent arterial spin labelling (ASL) study reported widespread decreases in cerebral blood flow (CBF). Because serotonergic drugs can also alter vascular tone, disentangling regional neuronal effects from global haemodynamic changes is important for interpreting pharmacological neuroimaging findings. Lewis and colleagues set out to resolve this contradiction by measuring cerebral perfusion after two oral doses of psilocybin using pseudo-continuous ASL (pCASL) in a randomised, double-blind, placebo-controlled design. They compared two analytic strategies: one that normalised for global perfusion to identify relative regional CBF (rCBF) changes, and one non-adjusted analysis to capture absolute or global CBF (gCBF) effects. The authors hypothesised that normalised analyses would reproduce the hyperfrontal pattern seen in PET, that non-adjusted analyses would show global decreases similar to the recent ASL report, and that the higher dose would produce larger effects than the lower dose.

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Study Details

References (20)

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