Psychedelics reopen the social reward learning critical period
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Abstract Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness 1,2 . These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies 3–9 . Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the ‘open state’ versus the ‘closed state’ provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.
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The therapeutic window during PAT represents the opening of a critical learning period that promotes plasticity in thought, emotion, behavior, and interpersonal relationships lasting approximately two weeks after an MDMA session.
“This window represents the opening of a critical learning period, that promotes plasticity in thought, emotion, behavior, and interpersonal relationships that lasts for approximately two weeks after an MDMA session (87).”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [87]
The Main section says MDMA reopens a critical period for social reward learning, and ‘Duration of the psychedelic open state’ says the MDMA-induced reopening lasts two weeks. But the two-week finding concerns social reward learning in mice, not a demonstrated therapeutic window after a human MDMA-assisted therapy session; the paper also does not establish plasticity across all the listed domains of thought, emotion, behavior, and interpersonal relationships. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe two weeks following MDMA administration is associated with increased neuroplasticity and psychological flexibility, making it an important time for integration.
“The two-weeks following MDMA administration is associated with increased neuroplasticity and psychological flexibility making it an important time for integration.”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [87]
The ‘Duration of the psychedelic open state’ section (page unavailable) says MDMA-induced reopening of the social reward learning critical period lasts two weeks in mice and links such open states to the importance of post-treatment integration. The Conclusions suggest that critical-period reopening may underlie psychological flexibility, but do not establish increased psychological flexibility throughout the two weeks after MDMA administration. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThis critical period is context-dependent and has been linked to the ability to induce social reward learning, psychological flexibility, cognitive reappraisal, and new patterns of behavior.
“This critical period is context-dependent and has been linked to the ability to induce social reward learning, psychological flexibility, cognitive reappraisal and new patterns of behavior (46, 48, 49).”
From Ayahuasca-assisted meaning reconstruction therapy for grief: a non-randomized clinical trial protocol (2025) · cites this paper as [46]
Psychedelics reopen a critical period to induce metaplasticity, which dynamically regulates the potential for synaptic plasticity.
“Recent studies have shown that psychedelics reopen a critical period to induce metaplasticity, which dynamically regulates the potential for synaptic plasticity (46, 47).”
From Ayahuasca-assisted meaning reconstruction therapy for grief: a non-randomized clinical trial protocol (2025) · cites this paper as [46]
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Psychedelic control of neuroimmune interactions governing fear
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- Authors
- Nardou, R., Sawyer, E., Song, Y. J., Wilkinson, M., Padovan-Hernandez, Y., de Deus, J. L., Wright, N., Lama, C., Faltin, S., Goff, L. A., Stein-O’Brien, G. L., & Dölen, G.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Dölen, Gül
- ORCID
- Venue
- Nature
- Published
- 2023-06-14
- Volume
- 618
- Issue
- 7966
- Pages
- 790-798
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC10284704
- OpenAlex
- W4380684709
- Cited by
- 358
- References
- 72
- Citations by year
- 2026: 100 · 2025: 147 · 2024: 80 · 2023: 30 · 2022: 1
- FWCI
- 104.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Johns Hopkins University
- National Institutes of Health
- National Institute on Aging (R01AG066768, R01AG072305)
- National Institute of Mental Health (R01MH117127)
- National Institute on Drug Abuse
- National Institute of General Medical Sciences (R25GM109441)
- National Institute of Neurological Disorders and Stroke (K99NS122085, R00NS122085)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD098184)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- psychedelics, metaplasticity, oxytocin, long-term depression, nucleus accumbens, extracellular matrix remodeling, subjective effects, altered states of consciousness
- MeSH terms
- Animals, Consciousness, Critical Period, Psychological, Extracellular Matrix, Hallucinogens, Humans, Learning, Nucleus Accumbens, Oxytocin, Reward, Time Factors, Long-Term Synaptic Depression, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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