Psilocybin Induced Psychedelic Experiences : their Neural Mechanisms and Efficacy for Treating Depressive Disorders

Abstract: The aim of this systematic review is to present the current literature on the therapeutic potential of the classic psychedelic compound psilocybin for depressive disorders and the neurocognitive mechanisms involved recorded with functional magnetic resonance imaging (fMRI). A comprehensive literature search was conducted in the electronic databases Web of Science, Scopus and Medline EBSCO using a Boolean search string containing the keywords psilocybin, depression, fMRI, MRI and PET. Our inclusion criteria require original neuroimaging research articles published in scientific peer-reviewed journals involving participants diagnosed with depression receiving psilocybin in conjunction with psychological support. Five articles were identified including a total of 104 participants with depression and 75 who received treatment, resulting in significant reduction of depressive symptoms associated with observable changes in neural activity. Specifically reduced cerebral blood flow (CBF) in amygdala, decreased brain modularity along with functional changes in default mode network (DMN), executive network (EN), salience network (SN), decrease in functional connectivity (FC) between ventromedial prefrontal cortex (vmPFC) to amygdala and increased amygdala reactivity to fearful faces. Limitations of our systematic review include a currently limited amount of articles published and thus lack of control groups in most studies. The current evidence indicates that the therapeutic potential of psilocybin-assisted therapy may provide fast acting and efficient amelioration of depressive symptoms and the effects may be mediated by neurocognitive changes acute and post-treatment. The preliminary results warrants further research in order to optimize treatment and establish safety and efficacy long term.