Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.
Robin Carhart-Harris, Leor Roseman, Mark Bolstridge, Lysia Demetriou, J Nienke Pannekoek, Matthew B. Wall, Mark Tanner, Mendel Kaelen, John Mcgonigle, Kevin Murphy, Robert Leech, Helen Valerie Curran, David Nutt
Sci Rep October 13, 2017 DOI: 10.1038/s41598-017-13282-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 19 |
| Population | Patients with treatment-resistant depression |
| Intervention | Psilocybin |
| Duration | 1-week and 5-week follow-up |
| Topics | Neuroplasticity Psilocybin Depression |
| Keywords | Psychedelic Depression treatment Antidepressant Mental health therapy Brain connectivity Neural networks Brain function Neuroimaging FMRI Functional MRI |
| Citations | 590 |
| Key findings | Psilocybin treatment decreased amygdala cerebral blood flow and increased default-mode network connectivity, with specific connectivity changes predicting clinical response at five weeks. |
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.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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Psilocybin treatment decreased amygdala cerebral blood flow and increased default-mode network connectivity, with specific connectivity changes predicting clinical response at five weeks; 47% met criteria for response at 5 weeks.
Synthesized
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Psilocybin treatment decreased amygdala cerebral blood flow and increased default-mode network connectivity, with specific connectivity changes predicting clinical response at five weeks.
Synthesized
Comparable studies
Other observational and cohort studies on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression Patients with treatment-resistant depression and healthy controls | 2017 | Observational cohort | n = 33 |
| More Realistic Forecasting of Future Life Events After Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression (TRD) | 2018 | Observational cohort | n = 15 |
| Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. 17 patients with treatment-resistant depression and 18 untreated age-matched healthy... | 2018 | Observational cohort with machine learning classification | n = 35 |
| Brain dynamics predictive of response to psilocybin for treatment-resistant depression. Responders and non-responders to psilocybin therapy for depression | 2024 | Observational cohort | |
| Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity. Patients with treatment-resistant depression or moderate-to-severe major depression | 2024 | Observational cohort | n = 38 |