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 Peer reviewed DOI: 10.64898/2026.04.06.716778 via PubMed
Summary
Psilocybin promotes the formation and maturation of synapses while also speeding up the elimination of existing synapses. The study indicates that serotonin 2A receptor signaling in cortical layer 5 pyramidal neurons is essential for the synaptic changes caused by psilocybin, but it is not necessary for a head-twitch response, which is used as a measure of hallucination in rodents.
Study at a glance
| Population | rodents |
|---|---|
| Key finding | 5-HT 2A R signaling in L5 PyrNs is necessary for psilocybin-induced synaptic remodeling but not 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.