Healthy VolunteersMajor Depressive Disorder (MDD)Depressive DisordersAnxiety DisordersNeuroimaging & Brain MeasuresPsilocybin

Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers

This double-blind, placebo-controlled, fMRI study (n=25) found that a moderate dose of psilocybin (11.2mg/70kg) lowered amygdala (which is hyperactive in those with major depression) reactivity to negative and neutral (visual) stimuli. The decrease in emotional processing was correlated with an increase in positive mood.

Authors

  • Erich Seifritz
  • Milan Scheidegger
  • Franz Vollenweider

Published

Biological Psychiatry
individual Study

Abstract

Background

The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change.

Methods

This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart.

Results

Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state.

Conclusions

These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression.

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Research Summary of 'Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers'

Introduction

Kraehenmann and colleagues frame the study around the amygdala's central role in serotonergic circuits for emotion processing and its consistent hyperactivity in major depression. Earlier research indicates that modulation of serotonin neurotransmission—such as with selective serotonin reuptake inhibitors (SSRIs)—reduces amygdala hyperreactivity and is associated with shifts toward more positive mood. Psychopharmacological and clinical evidence has further suggested that the hallucinogen psilocybin, a 5-HT1A/2A/2C agonist, can acutely induce positive mood changes and alter neural responses to emotional stimuli, but whether these effects include modulation of amygdala reactivity and how such modulation relates to mood change remained uncertain. This study set out to determine whether a single acute oral dose of psilocybin (0.16 mg/kg) reduces amygdala reactivity to negative stimuli in healthy volunteers and whether any change in amygdala activity relates to changes in mood. Using a placebo-controlled, double-blind, randomised cross-over design, the investigators combined task-based fMRI during an established amygdala reactivity paradigm with validated mood questionnaires to connect neural effects with subjective affective changes. The authors hypothesised that psilocybin would decrease amygdala reactivity to negative stimuli and increase positive mood state.

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Study Details

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