Amygdala response to emotional faces following acute administration of psilocybin in healthy individuals

The serotonergic psychedelic psilocybin acutely induces changes in emotional states. However, it remains unresolved whether psilocybin acutely modulates amygdala reactivity to emotions, a brain region critically involved in emotion processing. Using functional magnetic resonance imaging (fMRI), we examined in 26 healthy individuals whether amygdala responses to angry, fearful and neutral faces differ between acute exposure to psilocybin and at baseline. We also evaluated whether plasma psilocin levels (PPL) and subjective drug intensity (SDI) during psilocybin are related to amygdala responses to the emotional faces. We found that amygdala response to angry faces was significantly reduced during exposure to psilocybin as compared to baseline (mean difference = −0.54, PFWER = 0.03), whereas no significant changes in amygdala responses to fearful or neutral faces were observed. We further found that the amygdala response to fearful faces was significantly negatively associated with SDI (slope = −0.13, PFWER = 0.04), whereas no significant association with PPL was observed. Our findings indicate that psilocybin attenuates amygdala reactivity to angry faces and that a more intense subjective psilocybin response (SDI) is associated with attenuated amygdala reactivity to fearful faces, in accordance with previously reported results. Future studies should investigate whether exposure to psilocybin acutely changes emotion processing in individuals with depression and whether such changes are related to therapeutic outcomes.