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Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics
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Neural plasticity—the ability to change and adapt in response to stimuli—is an essential aspect of healthy brain function and, in principle, can be harnessed to promote recovery from a wide variety of brain disorders. Many neuropsychiatric diseases including mood, anxiety, and substance use disorders arise from an inability to weaken and/or strengthen pathologic and beneficial circuits, respectively, ultimately leading to maladaptive behavioral responses. Thus, compounds capable of facilitating the structural and functional reorganization of neural circuits to produce positive behavioral effects have broad therapeutic potential. Several known drugs and experimental therapeutics have been shown to promote plasticity, but most rely on indirect mechanisms and are slow-acting. Here, I describe psychoplastogens—a relatively new class of fast-acting therapeutics, capable of rapidly promoting structural and functional neural plasticity. Psychoplastogenic compounds include psychedelics, ketamine, and several other recently discovered fast-acting antidepressants. Their use in psychiatry represents a paradigm shift in our approach to treating brain disorders as we focus less on rectifying “chemical imbalances” and place more emphasis on achieving selective modulation of neural circuits.
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“In recent years, accumulating evidence indicates that psychedelic compounds that bind 5-HT 2A Rs rapidly promote neural plasticity both structurally and functionally, suggesting that this is a potential mechanism underlying the therapeutic effects of psychedelics (Olson, 2018;Inserra et al., 2021a;Kadriu et al., 2021).”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Olson, 2018
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“In recent years, accumulating evidence indicates that psychedelic compounds that bind 5-HT 2A Rs rapidly promote neural plasticity both structurally and functionally, suggesting that this is a potential mechanism underlying the therapeutic effects of psychedelics (Olson, 2018;Inserra et al., 2021a;Kadriu et al., 2021).”
From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Olson, 2018
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“Preliminary preclinical evidence suggests that psychedelics’ psychoplastogenic properties [44] might directly counteract the hypofrontality observed in chronic alcohol exposure [48], thereby restoring the function of the reflective prefrontal system and its regulatory action on the reward system.”
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“However, there is evidence that changes in neuroplasticity (e.g.changes in neurite growth, dendritic spine density, synapse number, intrinsic excitability, etc) important to reshape circuitries and connectivity can be produced even within 24 hours by compounds including ketamine, psychedelics and N-methyl-D-aspartate (NMDA) receptor partial agonists [Fig.3; (Olson, 2018).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Olson, 2018
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Šabanović, M., Lazari, A., Blanco-Pozo, M., Tisca, C., Tachrount, M., Martins-Bach, A. B., Lerch, J. P., Walton, M. E., & Bannerman, D. M. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02439-2 · Cited by 23
Haniff, Z. R., Bocharova, M., Mantingh, T., Rucker, J., Velayudhan, L., Taylor, D. M., Young, A. H., Aarsland, D., Vernon, A. C., & Thuret, S. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108641 · Cited by 21
Werle, I., & Bertoglio, L. J. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105899 · Cited by 24
Laabi, S., LeMmon, C., Vogel, C., Chacon, M., & Jimenez, V. M. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114940 · Cited by 20
Psychedelics action and schizophrenia
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How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder
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Macrodosing to microdosing with psychedelics: Clinical, social, and cultural perspectives
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Murphy, R. J., Godfrey, K. E. M., Shaw, A. D., Muthukumaraswamy, S. D., & Sumner, R. L. (2024) · BMC Neuroscience · doi:10.1186/s12868-024-00844-5 · Cited by 19
Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review
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Concurrent stress modulates the acute and post-acute effects of psilocybin in a sex-dependent manner
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Tombari, R. J., Mundy, P. C., Morales, K. M., Dunlap, L. E., Olson, D. E., & Lein, P. J. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00642 · Cited by 18
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Natural Psychoplastogens As Antidepressant Agents
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Psychedelics and schizophrenia: a double-edged sword
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Agrawal, R. G., Gillie, D. J., Mungenast, A. E., Chytil, M., Engel, S. R., Wu, M. C., Rasmussen, K., Salinas, E. O., & Olson, D. E. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00667 · Cited by 15
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Psychoactive Drugs in the Management of Post Traumatic Stress Disorder: A Promising New Horizon
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Metadata
- Authors
- Olson, D. E.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Olson, David E
- ORCID
- Olson, David E
- Venue
- Journal of Experimental Neuroscience
- Publisher
- SAGE Publications
- Published
- 2018-01
- Volume
- 12
- Pages
- 1179069518800508-1179069518800508
- ISSN
- 1179-0695 (ISSN-L)
- PMC
- PMC6149016
- OpenAlex
- W2892307734
- Cited by
- 257
- References
- 11
- Citations by year
- 2026: 47 · 2025: 44 · 2024: 49 · 2023: 39 · 2022: 38 · 2021: 19 · 2020: 15 · 2019: 6
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Experimental Neuroscience (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- National Institute of Child Health and Human Development (U54 HD079125)
- National Institute of General Medical Sciences (R01 GM128997)
- University of California, Davis (STAIR Grant)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- psychoplastogens, neuroplasticity, neurotherapeutics, psychedelics, ketamine, rapid-acting antidepressants, mood disorders, anxiety disorders, substance use disorders, neural circuit reorganization, neuropsychiatric disorders
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