Sex-sensitive serotonergic signaling in psychedelic pharmacology.

Authors

Sofia Nasini, Benedetta Barzon, Antonino Casile, Brandon Richardson, Gabriella Gobbi, Stefano Comai

Published in

Trends in pharmacological sciences. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Classic serotonergic psychedelics act primarily via 5-HT2A receptor agonism, yet their therapeutic effects and biological responses are heterogeneous. Biological sex remains an underexamined source of this variability because many clinical and preclinical studies have not been designed to test sex-by-treatment effects. Recent preclinical findings, together with more limited human evidence, suggest that sex and endocrine state can modulate serotonergic mechanisms relevant to psychedelic action, including 5-HT1A autoregulatory feedback, 5-HT2A signaling, serotonin clearance, neuroendocrine coupling, and neuroplastic cascades. This review synthesizes how sex- and state-sensitive serotonergic regulation may influence psychedelic signaling and outlines priorities for sex-informed translational research in preclinical and clinical settings.

PMID:
42575820
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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