Cognitive flexibility, cortical excitability and antidepressive effect of psilocybin

Serotonin (5-HT) is a neuromodulator implicated in the regulation of cognitive and behavioural processes, including cognitive flexibility. Conversely, manipulation of 5-HT circuits is a major tool in treatment of depression. Psilocybin, a 5-HT2A agonist, has recently been proposed to have fast and long-lasting antidepressant properties. It is thought to modify cortical excitability, which is altered in depression and modified by antidepressant treatment, namely repetitive transcranial magnetic stimulation. With this project we aim to (i) compare cognitive flexibility and cortical excitability between healthy subjects and depressed patients, (ii) assess antidepressant effects of psilocybin in depressed patients, as well as its impact on cognitive flexibility and cortical excitability and (iii) measure if potential impact of psilocybin on cognitive flexibility and cortical excitability is predictive of its antidepressant effects.