Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

In an open-label study, 20 individuals with moderate to severe, treatment-resistant depression received two doses of psilocybin with psychological support. Nineteen completed fMRI scans before and after treatment. Depressive symptoms improved rapidly and enduringly. Right amygdala responses to fearful and happy faces increased after psilocybin, and increased responses to fearful versus neutral faces predicted clinical improvement at one week. This contrasts with SSRIs, which typically reduce amygdala responses, suggesting psilocybin may help patients confront and work through emotions rather than dampen them. The authors propose psilocybin with psychological support revives emotional responsiveness in depression.

Study at a glance

Abstract

Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. TRIAL REGISTRATION: ISRCTN, number ISRCTN14426797. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.