This review (2022) explored results from neuroimaging studies with psilocybin. In studies with depressed patients, a decrease in amygdala activity and a reduction in depressive symptoms was observed while in healthy participants, changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala were observed.
“The use of psilocybin as treatment for major depressive disorder (MDD) has been examined as a promising alternative to traditional first-line options. We reviewed existing literature to provide a synthesis of the extant neuroimaging observations with psilocybin, and to identify putative therapeutic targets for target engagement studies with psilocybin, and potentially other psychedelics. We assessed neuroimaging observations with psilocybin among participants with MDD and healthy populations. A systematic search was conducted on PubMed, Google Scholar and PsycINFO from database inception to November 17th, 2021. The study quality (i.e., risk of bias) was assessed using the revised Cochrane risk-of-bias tool for randomized trials. A total of ten studies evaluated psilocybin in healthy populations and three studies assessed psilocybin in MDD participants using neuroimaging techniques. Following psilocybin administration, a decrease in amygdala activity and a reduction in depressive symptoms was observed in two studies. Changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala, was seen in healthy populations. There was high heterogeneity in methodology (e.g, dosing schedule and imaging methods) amongst included studies. Longitudinal studies are needed to further elucidate psilocybin treatment for MDD, its long-term effects and the possibility of sustained therapeutic effects.”
Authors: Hartej Gill, Parnian Puramat, Pankti Patel, Barjot Gill, CeAnn A. Marks, Nelson B. Rodrigues, David Castle, Danielle S. Cha, Rodrigo B. Mansur, Joshua D. Rosenblat & Roger S. McIntyre
Summary of The Effects of Psilocybin in Adults with Major Depressive Disorder and The General Population
Major depressive disorder is a chronic and debilitating mood disorder that impacts approximately 300 million individuals worldwide. Most individuals receiving evidence-based treatment for MDD do not achieve syndromal and functional recovery. Psychedelic medicines have been used for more than 2000 years for spiritual, religious, and healing purposes, but the therapeutic use of psychedelics is not currently recommended or approved by regulators due to insufficient safety, tolerability, and effectiveness data.
The therapeutic potential and safety of the classic psychedelics have been demonstrated in a number of clinical trials for the treatment of addiction, mood, and anxiety disorders. Psilocybin, a naturally occurring alkaloid, may be efficacious at rapidly reducing depressive symptoms in adults with MDD.