Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin.
Jacob J Baker, Emily Kogan, Shaorong Ma, Ju Lu, Yi Zuo
bioRxiv : the preprint server for biology June 18, 2026 DOI: 10.64898/2026.04.06.716778 via PubMed
Summary
AI-generated from the abstractPsilocybin promotes the formation and maturation of synapses while accelerating the elimination of pre-existing synapses. Signaling through serotonin 2A receptors in cortical layer 5 pyramidal neurons is necessary and sufficient for this synaptic remodeling but is not required for the head-twitch response, a rodent proxy for hallucination.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rodents |
| Intervention | Psilocybin |
| Key finding | Serotonin 2A receptor signaling in cortical layer 5 pyramidal neurons is necessary and sufficient for psilocybin-induced synaptic remodeling but dispensable for the head-twitch response. |
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.