Psilocybin enhanced positive mood and reduced recognition of negative facial expressions in healthy volunteers. It also increased goal-directed behavior toward positive emotional cues while inhibiting negative sequential emotional effects and valence-dependently attenuated the P300 brain response. These emotional shifts occurred across multiple psychological domains and were blocked by the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors is central to mood regulation and emotional face recognition. The findings suggest a mechanism for psilocybin's potential antidepressant effects.
The glutamate NMDA receptor and the serotonin 5-HT receptor system contribute differently to how the brain encodes emotional facial expressions. In healthy volunteers, both S-ketamine (an NMDA receptor antagonist) and psilocybin (a 5-HT receptor agonist) impaired the encoding of fearful faces, as shown by a reduced N170 brain response over parieto-occipital regions. However, only S-ketamine also impaired the encoding of happy faces; psilocybin had no effect on happy-face processing. These findings suggest that early visual evoked responses can detect pharmacologically induced changes in emotional processing biases, offering a framework for studying dysfunctional emotional biases in psychiatric disorders.