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

Biol Psychiatry. 2012 Dec 1;72(11):898-906. doi: 10.1016/j.biopsych.2012.04.005. Epub 2012 May 10.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiology
  • Double-Blind Method
  • Electroencephalography
  • Emotions / drug effects*
  • Emotions / physiology
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Female
  • Goals
  • Hallucinogens / pharmacology*
  • Humans
  • Ketanserin / pharmacology
  • Male
  • Neuropsychological Tests
  • Psilocybin / pharmacology*
  • Receptors, Serotonin / metabolism*
  • Recognition, Psychology / drug effects*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology


  • Hallucinogens
  • Receptors, Serotonin
  • Serotonin 5-HT2 Receptor Antagonists
  • Psilocybin
  • Ketanserin