Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Scientific Reports. 2017;7(1):1-11 DOI 10.1038/s41598-017-13282-7

 

Journal Homepage

Journal Title: Scientific Reports

ISSN: 2045-2322 (Online)

Publisher: Nature Publishing Group

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


Robin L Carhart-Harris (Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London)

Leor Roseman (Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London)

Mark Bolstridge (Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London)

Lysia Demetriou (Imanova Centre for Imaging Sciences, Burlington Danes Building, Hammersmith Hospital, Du Cane Road)

J Nienke Pannekoek (Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London)

Matthew B Wall (Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London)

Mark Tanner (Imanova Centre for Imaging Sciences, Burlington Danes Building, Hammersmith Hospital, Du Cane Road)

Mendel Kaelen (Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London)

John McGonigle (Imanova Centre for Imaging Sciences, Burlington Danes Building, Hammersmith Hospital, Du Cane Road)

Kevin Murphy (Cardiff University Brain Research Imaging Centre (CUBRIC), School of Physics and Astronomy)

Robert Leech (Computational, Cognitive and Clinical Neuroscience Laboratory (C3NL), Department of Medicine, Imperial College London)

H Valerie Curran (Clinical Psychopharmacology Unit, University College London, WC1E 6BT)

David J Nutt (Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 20 weeks

 

Abstract | Full Text

Abstract Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.