Psilocin fosters neuroplasticity in iPSC-derived human cortical neurons.
Målin Schmidt, Anne Hoffrichter, Mahnaz Davoudi, Sandra Horschitz, Thorsten Lau, Marcus W. Meinhardt, Rainer Spanagel, Julia Ladewig, Georg Köhr, Philipp Koch
Elife March 27, 2026 DOI: 10.7554/elife.104006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Human induced pluripotent stem cell-derived cortical neurons |
| Intervention | Psilocin |
| Topics | Neuroplasticity Psilocybin Serotonin |
| Keywords | Bdnf Psychedelics Human |
| Citations | 3 |
| Key findings | Psilocin, acting through the 5-HT2A receptor, increases BDNF abundance, primes neurons for neuroplasticity, enhances neuronal complexity and synaptic protein expression, and increases excitability and synaptic network activity. |
Abstract
Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated human cortical neurons derived from induced pluripotent stem cells with the 5-HT2A receptor agonist psilocin - the psychoactive metabolite of psilocybin. We analyzed how exposure to psilocin affects gene expression, neuronal morphology, synaptic markers and neuronal function. Psilocin provoked a 5-HT2A-R-mediated augmentation of BDNF abundance. Transcriptomic profiling identified gene expression signatures priming neurons to neuroplasticity. On a morphological level, psilocin induced enhanced neuronal complexity and increased expression of synaptic proteins, in particular in the postsynaptic compartment. Consistently, we observed an increased excitability and enhanced synaptic network activity in neurons treated with psilocin. In conclusion, exposure of human neurons to psilocin might induce a state of enhanced neuronal plasticity, which could explain why psilocin is beneficial in the treatment of neuropsychiatric disorders where synaptic dysfunctions are discussed.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 5
- The ABCs of psychedelics: a preclinical roadmap for drug discovery. TIPS - Trends in Pharmacological Sciences August 28, 2025
- The emotional architecture of the psychedelic brain Trends in Cognitive Sciences August 18, 2025
- Reshaping human neurons. Elife March 31, 2026
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics. Molecular Psychiatry July 28, 2026
- Mapping excitatory synaptic plasticity evoked by single-dose psilocybin in mice
Cites 37
- 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
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder The Journal of Clinical Psychiatry November 15, 2006
and 32 more in the library