Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors

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 behavioral effects of psilocybin and might be important for its recently suggested antidepressive effects. Howe...

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Veröffentlicht in:	Biological psychiatry (1969) Jg. 72; H. 11; S. 898 - 906
Hauptverfasser:	Kometer, Michael, Schmidt, André, Bachmann, Rosilla, Studerus, Erich, Seifritz, Erich, Vollenweider, Franz X.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York, NY Elsevier Inc 01.12.2012 Elsevier
Schlagworte:	Adult Adult and adolescent clinical studies Affect Affect - drug effects anxiety Biological and medical sciences Cerebral Cortex - drug effects Cerebral Cortex - physiology Depression Double-Blind Method Electroencephalography emotion Emotions - drug effects Emotions - physiology Evoked Potentials - drug effects Evoked Potentials - physiology Female Goals Hallucinogens - pharmacology Humans Ketanserin - pharmacology Male Medical sciences Mood disorders Neuropsychological Tests P300 Psilocybin - pharmacology Psychiatric/Mental Health Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptors, Serotonin - metabolism Recognition (Psychology) - drug effects serotonin Serotonin 5-HT2 Receptor Antagonists - pharmacology anxiety serotonin emotion depression Affect P300 Mood disorder Affect affectivity Serotonin Psychotropic Central nervous system Electrophysiology Depression Goal pursuit Cognition Emotion emotionality P300 potential Encephalon Mood Hallucinogen Neurotransmitter Anxiety Face Event evoked potential Psilocybine Recognition
ISSN:	0006-3223, 1873-2402, 1873-2402
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Abstract	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 behavioral 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. 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 behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues. Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior 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. 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.
AbstractList	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 behavioral 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.BACKGROUNDSerotonin (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 behavioral 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.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 behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues.METHODSIn 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 behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues.Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior 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.RESULTSPsilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior 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.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.CONCLUSIONSThis 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. 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 behavioral 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. 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 behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues. Psilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior 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. 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. BackgroundSerotonin (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 behavioral 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. MethodsIn 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 behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues. ResultsPsilocybin enhanced positive mood and attenuated recognition of negative facial expression. Furthermore, psilocybin increased goal-directed behavior 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. ConclusionsThis 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.
Author	Seifritz, Erich Kometer, Michael Schmidt, André Bachmann, Rosilla Vollenweider, Franz X. Studerus, Erich
Author_xml	– sequence: 1 givenname: Michael surname: Kometer fullname: Kometer, Michael email: michael.kometer@bli.uzh.ch organization: Neuropsychopharmacology and Brain Imaging, and Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland – sequence: 2 givenname: André surname: Schmidt fullname: Schmidt, André organization: Neuropsychopharmacology and Brain Imaging, and Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland – sequence: 3 givenname: Rosilla surname: Bachmann fullname: Bachmann, Rosilla organization: Neuropsychopharmacology and Brain Imaging, and Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland – sequence: 4 givenname: Erich surname: Studerus fullname: Studerus, Erich organization: Neuropsychopharmacology and Brain Imaging, and Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland – sequence: 5 givenname: Erich surname: Seifritz fullname: Seifritz, Erich organization: Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, Zurich, Switzerland – sequence: 6 givenname: Franz X. surname: Vollenweider fullname: Vollenweider, Franz X. organization: Neuropsychopharmacology and Brain Imaging, and Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland
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ISSN	0006-3223 1873-2402
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Issue	11
Keywords	anxiety serotonin emotion depression Affect P300 Mood disorder Affect affectivity Serotonin Psychotropic Central nervous system Electrophysiology Depression Goal pursuit Cognition Emotion emotionality P300 potential Encephalon Mood Hallucinogen Neurotransmitter Anxiety Face Event evoked potential Psilocybine Recognition
Language	English
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Snippet	Serotonin (5-HT) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders. These receptors further... BackgroundSerotonin (5-HT) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders. These receptors further...
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SubjectTerms	Adult Adult and adolescent clinical studies Affect Affect - drug effects anxiety Biological and medical sciences Cerebral Cortex - drug effects Cerebral Cortex - physiology Depression Double-Blind Method Electroencephalography emotion Emotions - drug effects Emotions - physiology Evoked Potentials - drug effects Evoked Potentials - physiology Female Goals Hallucinogens - pharmacology Humans Ketanserin - pharmacology Male Medical sciences Mood disorders Neuropsychological Tests P300 Psilocybin - pharmacology Psychiatric/Mental Health Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptors, Serotonin - metabolism Recognition (Psychology) - drug effects serotonin Serotonin 5-HT2 Receptor Antagonists - pharmacology
Title	Psilocybin Biases Facial Recognition, Goal-Directed Behavior, and Mood State Toward Positive Relative to Negative Emotions Through Different Serotonergic Subreceptors
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