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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The rapid promotion of neural plasticity by psychedelics is a potential mechanism underlying their therapeutic effects.
“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
Psychedelic compounds that bind 5-HT2A receptors rapidly promote neural plasticity both structurally and functionally.
“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
Preliminary preclinical evidence suggests that psychedelics' psychoplastogenic properties might directly counteract the hypofrontality observed in chronic alcohol exposure, thereby restoring the function of the reflective prefrontal system and its regulatory action on the reward system.
“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.”
Changes in neuroplasticity important to reshape circuitries and connectivity can be produced even within 24 hours by compounds including ketamine, psychedelics and NMDA receptor partial agonists.
“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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A lexicon for psychedelic research and treatment
Nutt, D. J., Erritzøe, D., Schlag, A. K., Luke, D. P., Mash, D. C., Uchida, H., Aday, J. S., Rucker, J., Galindo, L., Sweeney, M., et al. (2025) · Drug Science Policy and Law · doi:10.1177/20503245251380511 · Cited by 24 · see citing works
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Bedside to bench: the outlook for psychedelic research
Acero, V. P., Cribas, E. S., Browne, K. D., Rivellini, O. M., Burrell, J. C., O’Donnell, J. C., Das, S., & Cullen, D. K. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1240295 · Cited by 22 · see citing works
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 21 · see citing works
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Psychedelics action and schizophrenia
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Concurrent stress modulates the acute and post-acute effects of psilocybin in a sex-dependent manner
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Natural Psychoplastogens As Antidepressant Agents
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Psychedelics and schizophrenia: a double-edged sword
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Psychoactive Drugs in the Management of Post Traumatic Stress Disorder: A Promising New Horizon
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- 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 › 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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