Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers

  • Rainer Kraehenmann
    Address correspondence to Rainer Kraehenmann, M.D., University of Zürich, Department of Psychiatry, Psychotherapy and Psychosomatics, Neuropsychopharmacology and Brain Imaging, Psychiatric Hospital, Lenggstrasse 31, Zürich, ZH 8032, Switzerland
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland

    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Katrin H. Preller
    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Milan Scheidegger
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland

    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland

    Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich; and Institute for Biomedical Engineering, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Thomas Pokorny
    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Oliver G. Bosch
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Erich Seifritz
    Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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  • Franz X. Vollenweider
    Department of Neuropsychopharmacology and Brain Imaging, University of Zurich and Swiss Federal Institute of Technology, Zurich, Switzerland
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      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.


      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.


      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.


      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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      • Lysergic Acid Diethylamide and Psilocybin Revisited
        Biological PsychiatryVol. 78Issue 8
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          The past decade brought the beginnings of a renaissance in research on psychedelic drugs. Two articles in this issue of Biological Psychiatry signify that the resurrection of this long-ignored topic has begun to mature and bear at least the promise of fruit. In the early 1970s, the onset of the “War on Drugs” brought with it a near-total hiatus in serious research on psychedelic drugs, especially in the United States. The resumption of credible work in this area has come from Switzerland, where many of the original pioneering studies were initiated in the 1950s and 1960s.
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