Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination

Psilocybin, a psychedelic 5-HT2A receptor agonist, modulates emotion processing networks in the brain. In a double-blind crossover study with 18 healthy volunteers, psilocybin increased reaction time to emotional faces and decreased connectivity between the amygdala and the striatum during angry face discrimination, and between the amygdala and the frontal pole during happy face discrimination. No effect was seen during fearful face discrimination. These findings suggest psilocybin alters connectivity in key emotion-processing hubs, which may underlie its antidepressant effects, though further research is needed to link connectivity changes to therapeutic outcomes.

Study at a glance

Abstract

Recent studies suggest that the antidepressant effects of the psychedelic 5-HT2A receptor agonist psilocybin are mediated through its modulatory properties on prefrontal and limbic brain regions including the amygdala. To further investigate the effects of psilocybin on emotion processing networks, we studied for the first-time psilocybin's acute effects on amygdala seed-to-voxel connectivity in an event-related face discrimination task in 18 healthy volunteers who received psilocybin and placebo in a double-blind balanced cross-over design. The amygdala has been implicated as a salience detector especially involved in the immediate response to emotional face content. We used beta-series amygdala seed-to-voxel connectivity during an emotional face discrimination task to elucidate the connectivity pattern of the amygdala over the entire brain. When we compared psilocybin to placebo, an increase in reaction time for all three categories of affective stimuli was found. Psilocybin decreased the connectivity between amygdala and the striatum during angry face discrimination. During happy face discrimination, the connectivity between the amygdala and the frontal pole was decreased. No effect was seen during discrimination of fearful faces. Thus, we show psilocybin's effect as a modulator of major connectivity hubs of the amygdala. Psilocybin decreases the connectivity between important nodes linked to emotion processing like the frontal pole or the striatum. Future studies are needed to clarify whether connectivity changes predict therapeutic effects in psychiatric patients.