Reduced Brain Responsiveness to Emotional Stimuli With Escitalopram But Not Psilocybin Therapy for Depression
Matthew B. Wall, Lysia Demetriou, Bruna Giribaldi, Leor Roseman, Natalie Ertl, David Erritzøe, David Nutt, Robin Carhart-Harris
American Journal of Psychiatry May 7, 2025 DOI: 10.1176/appi.ajp.20230751 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | People with major depressive disorder |
| Intervention | Psilocybin therapy |
| Topics | Depression Psilocybin |
| Keywords | Cognitive neuroscience Depressive disorders Psychopharmacology Psychedelics hallucinogens Entheogens Antidepressants ssris Escitalopram Antidepressive agents Neuroimaging brain scanning Fm |
| Citations | 16 |
| Key findings | Psilocybin therapy had a minor effect on brain responsiveness to emotional stimuli despite large improvements in depressive symptoms, unlike SSRIs which typically reduce emotional responsiveness. |
Abstract
Despite large improvements in depressive symptoms in the psilocybin group, psilocybin therapy had only a minor effect on brain responsiveness to emotional stimuli. These results are consistent with prior findings that the antidepressant action of SSRIs is often accompanied by a reduction in emotional responsiveness, but this effect may not occur in psychedelic therapy.
Comparable studies
Other randomized controlled trials on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
| Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. Adults with treatment-resistant depression | 2022 | Phase 2 double-blind randomized controlled trial | n = 233 |
Citations in the library
Cited by 12
- The science of psychedelic medicine. Nature Medicine February 6, 2026
- Neurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans. Neuroscience & Biobehavioral Reviews August 1, 2025
- The emotional architecture of the psychedelic brain Trends in Cognitive Sciences August 18, 2025
- Temporal dynamics in neuroimaging as correlates of therapeutic response to psilocybin in major depressive disorder: A systematic review and critical appraisal Journal of Affective Disorders September 16, 2025
- Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin Molecular Psychiatry August 26, 2025
and 7 more in the library
Cites 43
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 38 more in the library