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 (Research Square) March 8, 2022 DOI: 10.21203/rs.3.rs-1321542/v1 via OpenAlex
Summary
AI-generated from the abstractPsilocybin, a psychedelic substance approaching clinical use, enhances structural plasticity in the brain. In cultured mouse hippocampal neurons, robust effects on pre- and postsynaptic protein expression (Piccolo and Homer1) appeared 1–3 hours after treatment, while presynaptic Synapsin-1 peaked at 72 hours, suggesting a rapidly normalizing window of plasticity. In an immortalized microglia cell line, psilocybin demonstrated anti-inflammatory effects against a lipopolysaccharide challenge by reducing tumor necrosis factor-alpha secretion. These discrete, acute cell-type-specific effects provide insight into psilocybin's mechanisms of action and potential therapeutic value for conditions like depression and cluster headache.
Study at a glance
| Characteristics | In vitro study Peer reviewed |
|---|---|
| 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 Neuroscience |
| Citations | 8 |
| Key finding | 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.