title: Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors.
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 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.
  
  
  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 behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: Neuropsychopharmacology and Brain Imaging, and Heffter Research Center, Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland. michael.kometer@bli.uzh.ch
authors.forename: Michael
authors.initials: M
authors.lastname: Kometer
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.forename: Rosilla
authors.initials: R
authors.lastname: Bachmann
authors.forename: Erich
authors.initials: E
authors.lastname: Studerus
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.forename: Franz X
authors.initials: FX
authors.lastname: Vollenweider
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004569:Electroencephalography; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006040:Goals; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009483:Neuropsychological Tests; D011562:Psilocybin / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: D006213:Hallucinogens; D011985:Receptors, Serotonin; D058830:Serotonin 5-HT2 Receptor Antagonists; D011562:Psilocybin; D007650:Ketanserin