Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin

bioRxiv (Cold Spring Harbor Laboratory) 2026 Preprint Open access

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Authors: Jacob J. Baker, Emily Kogan, Shaorong Ma, Ju Ming Lu, Yi Zuo
DOI: 10.64898/2026.04.06.716778
Cited by: 1
References: 37

Abstract

Abstract It is unclear how serotonin 2A receptors (5-HT 2A Rs) 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-HT 2A R 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.

Fields of Study & Subjects

Psychedelics and Drug Studies Forensic Toxicology and Drug Analysis Cannabis and Cannabinoid Research

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Publication date
9 April 2026
Language
EN
Document type
Preprint