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The Effects of Psilocybin in Adults with Major Depressive Disorder and the General Population: Findings from Neuroimaging Studies

Hartej Gill, Parnian Puramat, Pankti Patel, Barjot Gill, CéAnn A. Marks, Nelson B Rodrigues, David Castle, Danielle S. Cha, Rodrigo B. Mansur, Joshua D. Rosenblat, Roger S McIntyre

Psychiatry Research April 25, 2022 DOI: 10.1016/j.psychres.2022.114577 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Longitudinal Peer reviewed
Population Participants with major depressive disorder and healthy populations
Intervention Psilocybin
Topics Depression Psilocybin
Keywords Hallucinogen Clinical psychology Population Psycinfo Amygdala Functional neuroimaging Dorsolateral prefrontal cortex Cognition Medline
Citations 16
Key findings Psilocybin administration decreased amygdala activity and reduced depressive symptoms in MDD participants, and altered functional connectivity in prefrontal limbic structures in healthy populations.

Abstract

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.

Comparable studies

Other systematic reviews and meta-analyses on psilocybin for depression, most cited first.

Study Year Design Participants
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188
The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression 2020 Meta-analysis n = 117
Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders 2016 Systematic review n = 423
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... 2023 Systematic review with meta-analysis n = 14
Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression 2018 Systematic review n = 445

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