REVIEW article
Front. Neurosci.
Sec. Neuropharmacology
This article is part of the Research TopicBiological Drivers, Effects, and Mechanisms of Psychedelic-Induced Behavioral ChangeView all articles
Potential Molecular Pathways and Therapeutic Implications of Rapid-Acting Antidepressants on Myelin Biology: a Scoping Review
Provisionally accepted
- 1Universita degli Studi Gabriele d'Annunzio Chieti Pescara, Chieti, Italy
- 2Universidade do Sul de Santa Catarina - Campus Tubarao, Tubarão, Brazil
- 3University of Victoria, Victoria, Canada
- 4McGill University, Montreal, Canada
- 5University of Victoria Institute on Aging & Lifelong Health, Victoria, Canada
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Abstract Background: Emerging evidence indicates that rapid-acting antidepressants (RAADs)—including ketamine and serotonergic psychedelics-may affect myelin homeostasis, aside from producing fast-onset, sustained improvements in several psychiatric disorders. Methods. A systematic search of PubMed (MEDLINE), Web of Science, Europe PMC, Directory of Open Access Journals (DOAJ), and Google Scholar was conducted up to October 2025 for studies examining the effects of RAADs on myelination and oligodendrocyte biology, as well as associated molecular and cellular mechanisms. Main body. Forty-one studies met the inclusion criteria: 12 in humans, 21 in animals, 7 in vitro, and one computational/theoretical. Thirty studies investigated ketamine and 11 serotonergic RAADs. Across models, RAADs modulate myelination in a dose-and exposure-dependent manner: therapeutic doses generally promote myelin integrity and oligodendrocyte maturation, while high or repeated doses, or neonatal exposure, can disrupt myelin structure and function, impair oligodendrocyte viability, and produce cognitive, affective, and neurotoxic side effects. Conclusion. Myelin regulation may represent a component of RAAD action, indicating that these agents could influence myelin biology. Further research is required to clarify the mechanisms underlying these effects, their potential implications for therapies aimed at preserving or restoring myelin integrity, and potential side effects. Their dose-dependent effects highlight the need for careful consideration of dosing and treatment duration.
Keywords: rapid-acting antidepressants, Myelination, neuroplasticity, oligodendrocytes, NeuronalActivity-Dependent Myelination, Ketamine
Received: 21 Aug 2025; Accepted: 17 Dec 2025.
Copyright: © 2025 Inserra, Murray, Campanale, VanderZwaag and Tremblay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Antonio Inserra
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