Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
Open accessAbstract
Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. TRIAL REGISTRATION: ISRCTN, number ISRCTN14426797. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
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Greater amygdala responsiveness to fearful versus neutral faces was related to improved depressive symptoms 1 week post-intervention.
“The amygdala has been found to show greater responsiveness to emotional faces 1 day after psilocybin consumption and greater responsiveness to fearful versus neutral faces was related to improved depressive symptoms 1 week post-intervention [36].”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [36]
The amygdala has been found to show greater responsiveness to emotional faces 1 day after psilocybin consumption.
“The amygdala has been found to show greater responsiveness to emotional faces 1 day after psilocybin consumption and greater responsiveness to fearful versus neutral faces was related to improved depressive symptoms 1 week post-intervention [36].”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [36]
Increased amygdala reactivity toward fearful faces was measured prior to any psychological integration work.
“However, increased amygdala reactivity toward fearful faces was measured prior to any psychological integration work (31).”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [31]
Amygdala reactivity was increased in response to fearful faces in treatment-resistant depressed patients the morning after psilocybin administration.
“amygdala reactivity was increased in response to fearful faces in treatment-resistant depressed patients the morning after psilocybin administration (31).”
From Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019) · cites this paper as [31]
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- Authors
- Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J., & Carhart-Harris, R. L.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Roseman, Leor
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 142
- Pages
- 263-269
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2781340150
- Cited by
- 230
- References
- 57
- Citations by year
- 2026: 30 · 2025: 34 · 2024: 38 · 2023: 30 · 2022: 34 · 2021: 27 · 2020: 18 · 2019: 10 · 2018: 8 · 2017: 1
- FWCI
- 12.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neuropharmacology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Imperial College Scholarship Scheme
- Imanova
- Edmund J Safra Foundation (P17264)
- Alex Mosely Charitable Trust (G30444)
- MRC clinical development scheme (MR/J00460X/1)
- Alex Mosley Charitable Trust
- COMPASS group (I30006)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- psilocybin, treatment-resistant depression, amygdala, emotional face processing, fearful faces, happy faces, psychological support, selective serotonin reuptake inhibitors, antidepressant mechanism, emotional responsiveness
- MeSH terms
- Facial Recognition, Adult, Amygdala, Antidepressive Agents, Brain Mapping, Combined Modality Therapy, Emotions, Female, Hallucinogens, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Psilocybin, Psychotherapy, Depressive Disorder, Treatment-Resistant
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