Psilocybin Combines Rapid Synaptogenic And Anti-Inflammatory Effects In Vitro
Gabriella Smedfors, Elliot J. Glotfelty, Negar Kalani, Christian Papatziamos Hjelle, Otilia Horntvedt, Katrin Wellfelt, Alvin Brodin, Fredrik von Kieseritzky, Luis B. Tovar‐y‐romo, Tobias E. Karlsson
Research Square March 8, 2022 preprint DOI: 10.21203/rs.3.rs-1321542/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study |
|---|---|
| Population | Cultured mouse hippocampal neurons and immortalized microglia cell line (IMG) |
| Intervention | Psilocybin |
| Duration | 5 min to 72 h post-treatment |
| Topics | Psilocybin |
| Keywords | Hallucinogen Pharmacology Hippocampal formation |
| Citations | 8 |
| Key points | Psilocybin induces rapid, transient increases in synaptic protein expression in hippocampal neurons and reduces TNF-α secretion in microglia, indicating a short window of plasticity and anti-inflammatory effects. |
Abstract
Abstract Psilocybin is a psychedelic substance approaching clinical use. The drug has long-lasting effects after single or multiple administrations and enhances structural plasticity in the brain. Little is known if the plasticity inducing effects of psilocybin could be timed to other treatments and promote a larger effect. We investigated the effect of psilocybin on cultured mouse hippocampal neurons, examining the plasticity promoting effects from 5 min to 72 h post-treatment. We found robust effects on pre- and postsynaptic (Piccolo and Homer1) protein expression 1-3 h following treatment. Presynaptic Synapsin-1 expression mirrored these findings, with peak expression 72 h post-treatment. Our studies suggest psilocybin opens a window of plasticity that rapidly normalizes. As psilocybin has been shown to have an effect treating diseases (e.g. depression and cluster headache) linked with inflammation, we used an immortalized microglia cell line (IMG) to demonstrate its anti-inflammatory effects against a lipopolysaccharide (LPS) challenge (we show reduced tumor necrosis factor-alpha (TNF-α) secretion). Altogether, our studies show discrete and acute cell type specific effects of psilocybin that provides insight into its mechanisms of action and potential therapeutic value.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 6
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Psilocybin for the treatment of Alzheimer’s disease Frontiers in Neuroscience July 10, 2024
- Psychedelic Therapy: A Primer for Primary Care Clinicians-Psilocybin. American Journal of Therapeutics
- Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat Frontiers in Psychiatry August 6, 2025
- Psilocybin exerts differential effects on social behavior and inflammation in mice in contexts of activity-based anorexia Psychedelics February 3, 2026
and 1 more in the library
Cites 25
- 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
- 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
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 20 more in the library