Psilocybin is a promising treatment for depression that may match the efficacy of SSRIs, but their effects on brain responses to emotional stimuli have not been directly compared.

Methods: This study used BOLD fMRI to measure emotional face processing in two depression groups: one received two high-dose psilocybin sessions with placebo over six weeks (N=25), and the other received daily escitalopram with two placebo psilocybin sessions (N=21). Both groups received equivalent psychological support and completed emotional face fMRI scans before and six weeks after treatment.

Results: A significant interaction between treatment group and time was observed in various cortical regions. Escitalopram led to reduced BOLD responses to emotional faces and decreased amygdala activity to fearful expressions, whereas psilocybin showed no reduction or slight increases.

Conclusions: While both treatments improved depressive symptoms, psilocybin had minimal impact on emotional brain reactivity, suggesting that unlike SSRIs, its antidepressant effects may occur without dampening emotional responsiveness.

Source: https://psychiatryonline.org/doi/10.1176/appi.ajp.20230751