Depressive DisordersHealthy VolunteersPsilocybin

Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors

This randomised, double-blind, placebo-controlled crossover study (n=17) investigated whether 5-HT2A receptor activation mediates psilocybin’s effects on emotional processing. It finds that psilocybin (15 mg/70 kg) shifted emotional biases towards positive cues and reduced recognition of negative facial expressions, effects that were fully blocked by the antagonist ketanserin.

Authors

  • Erich Seifritz
  • Franz Vollenweider
  • Matthias Kometer

Published

Biological Psychiatry
individual Study

Abstract

Background

Serotonin (5-HT) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders. These receptors further predominantly mediate the subjective and behavioural effects of psilocybin and might be important for its recently suggested antidepressive effects. However, the effect of psilocybin on emotional processing biases and the specific contribution of 5-HT2A receptors across different emotional domains is unknown.

Methods

In a randomized, double-blind study, 17 healthy human subjects received on 4 separate days placebo, psilocybin (215 μg/kg), the preferential 5-HT2A antagonist ketanserin (50 mg), or psilocybin plus ketanserin. Mood states were assessed by self-report ratings, and behavioural and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behaviour toward emotional cues.

Results

Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behaviour toward positive compared with negative cues, facilitated positive but inhibited negative sequential emotional effects, and valence-dependently attenuated the P300 component. Ketanserin alone had no effects but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression.

Conclusions

This study shows that psilocybin shifts the emotional bias across various psychological domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects. These findings may not only have implications for the pathophysiology of dysfunctional emotional biases but may also provide a framework to delineate the mechanisms underlying psylocybin's putative antidepressant effects.

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Research Summary of 'Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors'

Introduction

Central to the pathophysiology of mood disorders is a bias toward the processing of negative relative to positive emotional information across perceptual, attentional, and behavioural domains. Depressed individuals demonstrate lower accuracy in recognising happy facial expressions, slower responses to positive stimuli, and altered neural responses to emotional cues — patterns that both reflect and perpetuate the affective state. Serotonin is believed to play a key regulatory role in such emotional processing biases, and the 5-HT2A receptor subtype in particular has been associated with emotional excitability and perceptual sensitivity. Psilocybin, a partial 5-HT2A agonist, has demonstrated antidepressant effects in clinical trials, but whether these reflect a correction of negative emotional processing biases — similar to the mechanism proposed for SSRIs — and whether 5-HT2A receptors specifically mediate these effects, had not been experimentally established. This study aimed to address this question directly using a double-blind, placebo-controlled, 2×2 factorial design with pharmacological blockade of the 5-HT2A receptor.

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Study Details

References (9)

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