CSF galanin and noradrenaline downregulation by psilocybin therapy in major depressive disorder
Wojciech Pasławski, Daniel Doyon, Carl Johan Ekman, Hampus Yngwe, Dejan Mamula, Justyna Zarȩba-pasławska, Maria Beckman, Qing Xu, Tomas Hökfelt, Mikael Tiger, Johan Lundberg, Per Svenningsson
Neuropsychopharmacology July 7, 2026 DOI: 10.1038/s41386-026-02490-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Secondary analysis of randomized, placebo-controlled trial Peer reviewed |
|---|---|
| Population | Participants with major depressive disorder |
| Intervention | Psilocybin |
| Topics | Depression Psilocybin |
| Keywords | Downregulation and upregulation Mechanism of action Galanin receptor Endogenous depression Endocrinology Pharmacology Pharmacodynamics Creb Depression economics Neuropeptide Major depressive episode Biomarker |
| Key findings | Psilocybin selectively reduced CSF galanin and noradrenaline, implicating normalization of these co-transmitters as a key pharmacodynamic signature. |
Abstract
Psilocybin is a rapid-acting antidepressant, but its mechanism of action in major depressive disorder remains unclear. In this secondary analysis of randomized, placebo-controlled trial with multimodal CSF and blood biomarker measurements, psilocybin selectively reduced CSF galanin and noradrenaline, implicating that normalization of these co-transmitters is a key pharmacodynamic signature.
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 |