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bioRxiv · 10.64898/2026.04.06.716778

Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin

Baker, J. J.·Kogan, E.·Lu, J.·Zuo, Y.
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Abstract

It is unclear how serotonin 2A receptors (5-HT2ARs) in cortical layer 5 pyramidal neurons (L5 PyrNs) differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Here we show that psilocybin promotes synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation further demonstrated that 5-HT2AR signaling in L5 PyrNs is necessary and sufficient for psilocybin-induced synaptic remodeling but dispensable for the head-twitch response, a rodent proxy of hallucination.

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Baker, J. J., Kogan, E., Lu, J., Zuo, Y.. 2026-04-09. Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin. https://doi.org/10.64898/2026.04.06.716778

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