Psilocybin improves depressive symptoms, with minor impact on brain responsiveness

Treatment with psilocybin results in significant improvements in depressive symptoms, and its use only shows a minor effect on brain responsiveness to emotional stimuli.

In a study, researchers examined neural responses to emotional faces using blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) in two groups with major depression.

The first group consisted of 25 patients (nine women and 16 men) and received two dosing sessions with psilocybin 25 mg plus 6 weeks of daily inert placebo. The second group included 21 patients (six women and 15 men) and received 6 weeks of escitalopram plus two dosing sessions with a nonpsychoactive (placebo) dose of psilocybin 1 mg.

Patients in both groups received equal psychological support: 3 h of preparation, one in-person integration session following the psilocybin dosing sessions, and two further integration sessions conducted via video call or telephone.

Participants also completed an emotional face fMRI paradigm before treatment and at the 6-week post-treatment primary endpoint (3 weeks after psilocybin dosing sessions).

The patient groups (psilocybin vs escitalopram) interacted with timepoints (before vs after treatment) on a distributed set of cortical regions.

In post hoc within-condition analyses, the escitalopram group showed significantly reduced post-treatment BOLD responses to emotional faces of all types. On the other hand, the psilocybin group showed no change or a slight increase.

In analyses of amygdala responsivity, the researchers observed a reduction of response to fearful faces in patients treated with escitalopram. Lesser effects were seen for those on psilocybin.

“Despite large improvements in depressive symptoms in the psilocybin group, psilocybin therapy had only a minor effect on brain responsiveness to emotional stimuli,” the researchers said. 

“These results are consistent with prior findings that the antidepressant action of SSRIs is often accompanied by a reduction in emotional responsiveness, but this effect may not occur in psychedelic therapy,” they added.