CSF galanin and noradrenaline downregulation by psilocybin therapy in major depressive disorder
Wojciech Pasławski, D 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 via OpenAlex
Summary
AI-generated from the abstractPsilocybin, a rapid-acting antidepressant, reduces levels of the neuropeptide galanin and noradrenaline in cerebrospinal fluid, suggesting that normalization of these co-transmitters is a key pharmacodynamic effect. This finding comes from a secondary analysis of a randomized, placebo-controlled trial with multimodal biomarker measurements. The results indicate a selective effect of psilocybin on these specific neurotransmitters, offering insight into its mechanism of action in major depressive disorder.
Study at a glance
| 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 |
| Key finding | 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.