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
Research Square June 7, 2024 preprint DOI: 10.21203/rs.3.rs-4242829/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Human cortical neurons derived from induced pluripotent stem cells |
| Intervention | psilocin |
| Topics | Neuroplasticity Psilocybin |
| Keywords | Cortical neurons |
| Citations | 5 |
| Key findings | Psilocin exposure induces enhanced neuronal plasticity in human cortical neurons, characterized by increased complexity, synaptic protein expression, and network activity. |
Abstract
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 5-HT2A receptor localization, gene expression, neuronal morphology, synaptic markers and neuronal function. Upon exposure of human neurons to psilocin, we observed a decrease of cell surface-located 5-HT2A receptors first in the axonal- followed by the somatodendritic-compartment. Psilocin further 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 induces 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 experimental studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics Promote Structural and Functional Neural Plasticity Neurons in vitro and in vivo | 2018 | Laboratory study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Focused attention meditation changes the boundary and configuration of functional networks in the brain One human participant | 2020 | Single-case experimental design with intensive longitudinal data | n = 1 |
| Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation. Rat brain models | 2002 | Review with experimental data |
Citations in the library
Cited by 2
Cites 38
- 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
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- 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
and 33 more in the library