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.

Details

Title
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms
Author
Carhart-Harris, Robin L 1 ; Roseman, Leor 2 ; Bolstridge, Mark 1 ; Demetriou, Lysia 3 ; Pannekoek, J Nienke 4 ; Wall, Matthew B 5 ; Tanner, Mark 6 ; Mendel Kaelen 1 ; McGonigle, John 6 ; Murphy, Kevin 7 ; Leech, Robert 8 ; Curran, H Valerie 9 ; Nutt, David J 1 

 Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London, London, UK 
 Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London, London, UK; Computational, Cognitive and Clinical Neuroscience Laboratory (C3NL), Department of Medicine, Imperial College London, London, UK 
 Imanova Centre for Imaging Sciences, Burlington Danes Building, Hammersmith Hospital, Du Cane Road, London, UK; Investigative Medicine, Department of Medicine, Imperial College London, London, United Kingdom 
 Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London, London, UK; SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, South Africa 
 Psychedelic Research Group, Psychopharmacology Unit, Centre for Psychiatry, Department of Medicine, Imperial College London, London, UK; Clinical Psychopharmacology Unit, University College London, WC1E 6BT, London, United Kingdom; Imanova Centre for Imaging Sciences, Burlington Danes Building, Hammersmith Hospital, Du Cane Road, London, UK 
 Imanova Centre for Imaging Sciences, Burlington Danes Building, Hammersmith Hospital, Du Cane Road, London, UK 
 Cardiff University Brain Research Imaging Centre (CUBRIC), School of Physics and Astronomy, Cardiff, UK 
 Computational, Cognitive and Clinical Neuroscience Laboratory (C3NL), Department of Medicine, Imperial College London, London, UK 
 Clinical Psychopharmacology Unit, University College London, WC1E 6BT, London, United Kingdom 
Pages
1-11
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1957857306
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.