Psilocybin Combines Rapid Synaptogenic And Anti-Inflammatory Effects In Vitro

Introduction

The introduction frames the central nervous system as a generally growth-inhibitory environment maintained by factors such as the Nogo signalling system, while neurotrophins like BDNF and GDNF act to oppose that restriction and promote structural plasticity. Interest in pharmacological agents that enhance neuronal plasticity has revived with research on serotonergic psychedelic compounds, several of which have been reported to induce neurite outgrowth, spine formation and synaptogenesis. Psilocybin, a prodrug rapidly dephosphorylated to the active metabolite psilocin, engages serotonergic receptors (notably 5-HT2A) and is under clinical investigation for several neuropsychiatric conditions; however, mechanisms underlying its rapid and long-lasting effects on synaptic and immune-related processes remain poorly defined. Smedfors and colleagues set out to characterise acute and short-term cellular effects of psilocybin in vitro, focusing on synaptic markers in primary mouse hippocampal and cortical neuronal cultures and on inflammatory responses in an immortalised microglial (IMG) cell line. The study aims to map time courses of pre- and postsynaptic protein expression from minutes to days after exposure, to assess regional specificity (hippocampus versus cortex), and to test whether psilocybin modulates microglial cytokine release after an LPS challenge, thereby probing both plasticity-promoting and anti-inflammatory actions.