Potential molecular pathways and therapeutic implications of rapid-acting antidepressants on myelin biology: a scoping review.
Antonio Inserra, Colin J. Murray, Antonella Campanale, Jared VanderZwaag, Marie-Ève Tremblay
Frontiers in Neuroscience 2025 DOI: 10.3389/fnins.2025.1690318 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Interventions | Ketamine serotonergic psychedelics |
| Topics | Ketamine Neuroplasticity |
| Keywords | Neuronal activity-dependent myelination Oligodendrocytes Rapid-acting antidepressants |
| Key findings | Rapid-acting antidepressants modulate myelination in a dose- and exposure-dependent manner, with therapeutic doses promoting myelin integrity and high or repeated doses disrupting it. |
Abstract
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. 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. 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. 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.
Comparable studies
Other systematic reviews and meta-analyses on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Systematic review of 20 studies (16 preclinical, 4 clinical) | 2021 | Systematic review | |
| Neurobiological Changes Induced by Mindfulness and Meditation: A Systematic Review. | 2024 | Systematic review | |
| Mindfulness-Based Cognitive Therapy in Clinical Practice: A Systematic Review of Neurocognitive Outcomes and Applications for Mental Health and Well-Being. | 2025 | Systematic review | |
| Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. | 2025 | Systematic review | |
| Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD. | 2025 | Systematic review |
Citations in the library
Cites 44
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
and 39 more in the library