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Here, we characterize the effects of psilocybin on dendritic calcium dynamics in pyramidal tract neurons of the mouse medial frontal cortex. Psilocybin transiently increases calcium event rates in apical dendritic tufts over a time course that parallels the drug\u2019s pharmacokinetics in the brain. This acute effect is brain state-dependent, occurring selectively during quiet wakefulness, and was abolished by cell type-specific deletion of the 5-HT\n                  <jats:sub>2A<\/jats:sub>\n                  receptor. Under control conditions, dendritic calcium signaling predicts subsequent spine formation, but this relationship is not preserved following psilocybin administration. Together, these findings reveal that psilocybin engages brain state- and 5-HT\n                  <jats:sub>2A<\/jats:sub>\n                  receptor-dependent dendritic signaling, while altering the relationship between acute dendritic activity and long-term structural plasticity. The results suggest that the mechanisms linking acute dendritic signaling to structural remodeling differ between physiological and psychedelic-induced plasticity.\n                <\/jats:p>","DOI":"10.64898\/2026.07.16.738983","type":"posted-content","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:20:19Z","timestamp":1784560819000},"source":"Crossref","is-referenced-by-count":0,"title":["Psychedelic drug action at dendrites is gated by behavioral state and serotonin receptors"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-4466","authenticated-orcid":false,"given":"Neil K.","family":"Savalia","sequence":"first","affiliation":[{"name":"Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA"},{"name":"Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA"},{"name":"Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT 06511, 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