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Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.

Giacomo D’andrea, Stefania Chiappini, Laura Ciavoni, Rolando Tucci, Fabrizio Martino, Francesco Maria Semeraro, Daniele Di Battista, Alessio Mosca, Andrea Miuli, Francesco Di Carlo, Mirella Russo, Gilberto Di Petta, Michele Fornaro, Mauro Pettorruso, Stefano L. Sensi, Giovanni Martinotti

Transl Psychiatry October 31, 2025 DOI: 10.1038/s41398-025-03654-3 via PubMed Central

Summary

AI-generated from the abstract

Psychedelics and ketamine/esketamine show promise for treating depressive disorders by inducing rapid and sustained antidepressant effects. The review examines their biological mechanisms, including modulation of glutamate and serotonin systems, promotion of neuroplasticity, and changes in brain connectivity and network function. Neuroimaging studies reveal alterations in default mode network, fronto-limbic connectivity, and thalamic activity. Clinical changes are associated with these brain alterations, though the precise relationships remain under investigation. The work synthesizes current evidence on how these compounds produce observable brain changes and symptom improvement, highlighting the need for further research to clarify mechanisms and optimize therapeutic applications.

Study at a glance

Characteristics Review Peer reviewed
Interventions Psychedelics Ketamine Esketamine
Topics Depression Ketamine Neuroplasticity Psychedelic-assisted therapy
Keywords Psychedelics Compounds Innovative therapies
Citations 3
Key finding Psychedelics and ketamine/esketamine produce antidepressant effects through modulation of glutamate and serotonin systems, promotion of neuroplasticity, and alterations in brain connectivity and network function, as observed in neuroimaging studies.

Abstract

Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.

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