Psilocybin Combines Rapid Synaptogenic And Anti-Inflammatory Effects In Vitro

This in vitro study (2022) assessed the effect neuroplastic and inflammatory effects of psilocybin. Findings suggest that psilocybin opens a window of plasticity that rapidly normalizes while it reduced levels of tumour necrosis factor-alpha (TNF-α) secretion demonstrating its anti-inflammatory effects.


“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 tumour 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.”

Authors: Gabriella Smedfors, Elliot Glotfelty, Negar Kalani, Christian P. Hjelle, Otilia Horntvedt, Katrin Wellfelt, Alvin Brodin, Fredrik von Kieseritzky, Lars Olson & Tobias Karlsson

Study details

Compounds studied

Topics studied
Immunity Neuroscience

Study characteristics

0 Humans


Institutes associated with this publication

Karolinska Institutet
KI is Sweden’s single largest centre of medical academic research which as expanded into the field of psychdelics.

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