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Neuroplasticity

The brain's capacity to reorganize, a leading candidate mechanism for the lasting effects of psychedelics and learning.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Neuroplasticity, neural plasticity, brain plasticity, synaptic plasticity, neurogenesis, then ranked by relevance.

Research indicates that both meditation and psychedelic compounds (e.g., psilocybin, LSD, DMT, ketamine) can promote neuroplasticity, including increased cortical thickness, dendritic growth, and synaptic changes, with some studies linking these changes to improved clinical outcomes. However, the evidence is mixed regarding the durability of these effects and the specific mechanisms involved, and many studies are limited by small sample sizes and open-label designs.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Meditation experience is associated with increased cortical thickness 2005
Supports

Meditation experience was associated with increased cortical thickness in attention, interoception, and sensory processing regions, suggesting experience-dependent cortical plasticity.

observational Sample size: 20

Psychedelics Promote Structural and Functional Neural Plasticity 2018
Supports

Serotonergic psychedelics robustly increased neuritogenesis and spinogenesis in vitro and in vivo, accompanied by increased synapse number and function, via TrkB, mTOR, and 5-HT2A signaling.

preclinical

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. 2017
Supports

Psilocybin treatment was associated with decreased depressive symptoms, decreased amygdala cerebral blood flow, and increased default-mode network connectivity, suggesting a 'reset' mechanism.

open-label Sample size: 19

Functional Reorganization of the Default Mode Network across Chronic Pain Conditions 2014
Mixed

Chronic pain was associated with decreased default-mode network connectivity to medial prefrontal cortex and increased connectivity to insular cortex, reflecting maladaptive neuroplasticity.

observational

Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors 2023
Supports

Psychedelics promote neuroplasticity through activation of intracellular 5-HT2A receptors, explaining why serotonin does not engage similar plasticity mechanisms.

preclinical

Psychedelics promote plasticity by directly binding to BDNF receptor TrkB 2023
Supports

LSD and psilocin directly bind to TrkB with high affinity, promoting neuroplasticity and antidepressant-like behavior in mice, independent of 5-HT2A activation.

preclinical

Increased global integration in the brain after psilocybin therapy for depression. 2022
Supports

Psilocybin therapy for depression was associated with increased global integration in the brain.

observational

Emotions and brain function are altered up to one month after a single high dose of psilocybin. 2020
Supports

A single high dose of psilocybin increased emotional and brain plasticity, with reduced negative affect and amygdala response at one week, and increased positive affect and resting-state functional connectivity at one month.

open-label Sample size: 12

Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. 2021
Supports

Psilocybin therapy increased cognitive flexibility for at least four weeks, with changes in glutamate and N-acetylaspartate concentrations and increased dynamic functional connectivity between the anterior and posterior cingulate cortex.

open-label Sample size: 24

LSD-induced entropic brain activity predicts subsequent personality change. 2016
Supports

LSD increased brain entropy globally, and these shifts predicted enduring increases in the personality trait openness at two-week follow-up.

RCT Sample size: 19

Towards an understanding of psychedelic-induced neuroplasticity. 2023
Supports

Classic psychedelics promote neuroplasticity through dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes, with effects lasting months to years.

review

Effective connectivity changes in LSD-induced altered states of consciousness in humans. 2019
Supports

LSD altered effective connectivity within cortico-striato-thalamo-cortical pathways, increasing thalamus-to-posterior cingulate cortex connectivity via 5-HT2A activation, supporting the thalamic filter model.

RCT Sample size: 25

State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect 2016
Supports

Forty days of mindfulness meditation training was associated with changes in resting-state functional connectivity and reduced depression/anxiety scores, suggesting neuroplastic changes.

observational Sample size: 13

Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics 2021
Supports

A single administration of a psychedelic produces rapid changes in plasticity mechanisms at molecular, neuronal, synaptic, and dendritic levels, including changes in BDNF expression.

review

Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. 2019
Supports

Psilocybin modulated the dynamical exploration of the repertoire of brain networks at rest.

observational

Network dysregulation in depression: A synthesis of HPA Axis, BDNF signaling, and neurotransmitter interactions across multidimensional systems. 2026
Supports

The BDNF/CREB signaling pathway is proposed as a core hub mediating multisystem network dysfunction in depression, with antidepressant interventions targeting this pathway to promote neuroplasticity.

review

Brain-targeted epigenetic effects of two emerging psychoplastogens: ketamine & MDMA 2026
Supports

Ketamine and MDMA were associated with peripheral epigenetic changes in pathways related to neuroplasticity and neuroimmune regulation.

observational Sample size: 36

ProliferativeEffects of the Psychedelic N,N-Dimethyltryptamine(DMT) in Human Neural Stem Cells 2026
Supports

Brief DMT exposure increased proliferation of human neural stem cells in a concentration-dependent manner and upregulated BDNF transcripts and protein.

preclinical

Treating addiction with an addictive drug: the ketamine paradox revisited 2026
Supports

Ketamine combined with psychotherapy showed promising reductions in craving and increases in abstinent days in small-to-moderate sized Phase 2 trials for alcohol and cocaine use disorders.

review

A conceptual framework based on current and emerging treatments for treatment-resistant depression: mechanistic evolution, clinical evidence, and future directions. 2026
Supports

Treatment-resistant depression is conceptualized as impaired neural adaptability, with treatments like ketamine, neuromodulation, and psychedelics reopening plasticity windows and recalibrating dysfunctional networks.

review

Chronic psilocin microdosing produces limited behavioral effects and does not enhance neurogenesis in rats. 2026
No effect

Chronic psilocin microdosing did not affect locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase dentate gyrus cell proliferation.

preclinical

Ketamine renaissance: Expanding horizons from anesthesia to depression and pain 2026
Supports

Ketamine modulates glutamatergic neurotransmission, enhancing synaptic plasticity and influencing neuroinflammatory pathways, with rapid antidepressant action in treatment-resistant depression.

review

Psilocybin reduces fear memory and restores neuroplasticity in the hippocampus and medial prefrontal cortex. 2026
Supports

Psilocybin reduced fear memory and restored neuroplasticity in the hippocampus and medial prefrontal cortex, increasing dendritic branches and spine density.

preclinical

Art as Neuroplastogens 2026
Unclear

The paper argues that immersive algorithmic art can function as a non-pharmacological intervention to enhance neural plasticity through prediction-error signaling, but this is a theoretical proposal without empirical data.

theoretical

A Critical Evaluation of the Hypothesis that N,N-Dimethyltryptamine Maintains Neuroplasticity 2026
Mixed

The hypothesis that endogenous DMT maintains neuroplasticity is supported by some evidence (e.g., DMT promotes synaptic growth and BDNF expression) but is contested due to detection limits, unreplicated findings, and lack of direct dietary measurements.

review

Points of agreement

  • Multiple studies indicate that both meditation and psychedelic compounds can induce structural and functional neuroplastic changes in the brain.
  • Psychedelics (psilocybin, LSD, DMT, ketamine) promote neuroplasticity through mechanisms involving BDNF, TrkB, mTOR, and 5-HT2A signaling pathways.
  • Clinical improvements in depression, anxiety, and PTSD are associated with these neuroplastic changes, suggesting therapeutic potential.

Conflicts

  • Some studies show that microdosing psilocin does not produce neuroplastic effects (e.g., no increase in neurogenesis in rats), contrasting with findings from higher doses.
  • The role of endogenous DMT in maintaining neuroplasticity is contested, with some studies failing to detect DMT in the brain and others questioning the relevance of its receptor affinities.
  • While many studies report positive effects on neuroplasticity, the durability and clinical significance of these changes vary across studies.

Gaps

  • Long-term durability of neuroplastic changes induced by psychedelics and meditation is not well-established.
  • Most clinical studies have small sample sizes and are open-label, lacking rigorous blinding and control conditions.
  • The specific dose-response relationships for neuroplasticity effects (e.g., microdosing vs. full doses) are not fully characterized.
  • The translation of preclinical findings to human neuroplasticity and clinical outcomes remains incomplete.
  • The role of endogenous DMT in neuroplasticity and its decline with age is not conclusively demonstrated.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Neuroplasticity, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Neuroplasticity or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: June 2026 →

1,279 articles · 722 from the last two years · 29,891 participants across 187 studies reporting sample size

Common study designs

review 382 experimental study 109 observational cohort 59 randomized controlled trial 54 theoretical or philosophical paper 167

Research

Synthesize the evidence → Search all →

Antidepressant-like effects of ketamine involve CX3CL1/CX3CR1 signaling-mediated synaptic plasticity in the mPFC

Translational Psychiatry July 20, 2026 Yong-Yu Yin, Si-Rui Sun, Hui-Ying Zhang et al.

Ketamine, a fast-acting antidepressant, works in part by blocking a signaling pathway between immune cells and neurons in the brain. In mice with depression-like symptoms caused by corticosterone, a single dose of ketamine (10 mg/kg) reversed behavioral deficits, reduced inflammation, and restored the structure of brain cells. Blocking the CX3CL1/CX3CR1 signaling pathway—either with a drug or by silencing the gene—eliminated both the behavioral and brain-cell benefits of ketamine. This suggests that this chemokine pathway is essential for ketamine's antidepressant effects and could be a new target for treating depression.

DOI: 10.1038/s41398-026-04242-9 (opens in new tab) Full text (opens in new tab) Synaptic plasticity Ketamine Neuroplasticity Microinjection +10

Post-Perturbation Integrative Neuroplasticity (PPIN): A Descriptive Framework for Non-Pathological Cross-Domain Cognitive Reorganization

Zenodo (CERN European Organization for Nuclear Research) July 18, 2026 Aziel Eliab

Post-Perturbation Integrative Neuroplasticity (PPIN) is a descriptive framework for broad, non-pathological cognitive reorganization after severe trauma, near-death experiences, or extreme stress. Unlike acquired savant syndrome, which produces narrow skill emergence, PPIN describes cross-domain integration, systems-level thinking, and heightened pattern sensitivity while preserving executive function, reality testing, and adaptive functioning. It distinguishes PPIN from psychotic conditions, manic states, and post-traumatic growth by emphasizing preserved falsifiability, identity restraint, and functional outcomes. The framework provides a neutral vocabulary for documenting cognitive changes without pathologization or over-attribution of special status, with inclusion and exclusion criteria, differential comparisons, mechanistic hypotheses, and ethical guardrails. PPIN is proposed as a research-oriented construct, not a clinical diagnosis or identity category.

DOI: 10.5281/zenodo.21430081 (opens in new tab) Neuroplasticity Cognition Adaptive functioning Construct python library +8

Psilocybin's effect on human brain synaptic plasticity.

Translational Psychiatry July 15, 2026 Annette Johansen, Pontus Plavén-sigray, Martin K Madsen et al.

A single dose of psilocybin (0.3 mg/kg) did not produce a statistically significant increase in synaptic density across all fifteen healthy participants. However, those who received psilocybin in a therapeutic-like room reported more intense mystical-type experiences, longer-lasting psychological benefits, and showed greater increases in synaptic density in the frontal cortex and hippocampus compared to those dosed inside an MRI scanner. The findings indicate that environmental context modulates psilocybin's neuroplastic effects, with implications for psychedelic-assisted therapies.

DOI: 10.1038/s41398-026-04285-y (opens in new tab) Full text (opens in new tab)

Brain and Environment Interaction: Neuroplasticity of the Visual Cortex and the Roles of Sensory Deprivation, Sleep, and Dreams.

Psychiatry July 6, 2026 Rehana K Naik Olson, Lawrence Wichlinski

The adult visual cortex, once thought to be rigid and unchangeable, retains some capacity for neuroplastic change, which can be influenced by environmental factors such as visual deprivation. The Defensive Activation Theory (DAT) proposes that dreaming during rapid eye movement sleep helps prevent loss of visual function during the visual deprivation that occurs nightly. This review examines evidence for visual cortical plasticity across the human lifespan and the roles of sleep and dreaming in mediating that plasticity, concluding that adult neuroplasticity contributes to functional outcomes and that sleep plays a mediating role.

DOI: 10.1080/00332747.2026.2680659 (opens in new tab) Full text (opens in new tab)

Chronic psilocin microdosing produces limited behavioral effects and does not enhance neurogenesis in rats.

Pharmacology, biochemistry, and behavior June 30, 2026 Lucie Ladislavová, Viera Kútna, Kristýna Mazochová et al.

Chronic microdosing of psilocin (0.05 or 0.075 mg/kg) in adult male Wistar rats over five weeks did not alter locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase cell proliferation in the dentate gyrus of the hippocampus. A small anxiogenic effect was detected in the Elevated Plus Maze. The findings suggest that, under this dosing schedule, psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation.

DOI: 10.1016/j.pbb.2026.174231 (opens in new tab) Full text (opens in new tab) Anxiety Depression Behavioral testing Hippocampal neurogenesis +3

Psilocybin reduces fear memory and restores neuroplasticity in the hippocampus and medial prefrontal cortex.

J Psychopharmacol June 28, 2026 Yingjie Du, Xiangting Zhao, Yishan Yao et al.

In a mouse model of posttraumatic stress disorder, a single dose of psilocybin reduced fear responses to a conditioned cue measured 1, 6, and 7 days later. Psilocybin also reversed the fear conditioning-induced reductions in neuroplasticity in the hippocampus and medial prefrontal cortex, increasing dendritic branches and spine density, upregulating GluR1 and synapsin-1, enhancing brain-derived neurotrophic factor and mammalian target of rapamycin signaling, and promoting neurogenesis. These results suggest that psilocybin may have therapeutic potential for PTSD and other disorders involving fear memory by restoring neuroplasticity in these brain regions.

DOI: 10.1177/02698811261453819 (opens in new tab)

A Critical Evaluation of the Hypothesis that N,N-Dimethyltryptamine Maintains Neuroplasticity

Zenodo (CERN European Organization for Nuclear Research) June 24, 2026 Ramiro Solis

The brain's ability to rewire itself declines with age, but why remains unclear. This paper examines whether the compound N,N-dimethyltryptamine (DMT) helps maintain neuroplasticity, and whether its decline contributes to age-related loss of cognitive flexibility. DMT promotes synaptic growth and neurogenesis in animals, and levels are reportedly highest during development. However, evidence is mixed: one study finds DMT concentrations comparable to serotonin, while another finds it undetectable in rat brain. DMT's affinity for the sigma-1 receptor is three orders of magnitude higher than physiological concentrations, and a key finding about intracellular 5-HT2A receptor binding has not been replicated. The paper does not claim the hypothesis is established, but proposes a research program to test whether DMT depletion causes lost plasticity or is incidental.

DOI: 10.5281/zenodo.20824129 (opens in new tab) Neuroplasticity Serotonin Endogeny Antidepressant +7

IARS Emery Brown Award 2026: Anesthetics and Serotonergic Psychedelics May Promote Therapeutic Neuroplasticity by Destabilizing Pathological Neuronal Circuitry.

Anesth Analg June 16, 2026

Anesthetics and serotonergic psychedelics may promote therapeutic neuroplasticity by destabilizing pathological neuronal circuitry, according to a theoretical argument. The work suggests that these compounds could help rewire dysfunctional brain networks, potentially offering a mechanism for their therapeutic effects.

DOI: 10.1213/ane.0000000000008168 (opens in new tab)

Ketamine and Evolving Neuroplasticity.

Clinical drug investigation June 13, 2026 Angel Prabakar

Ketamine provides rapid antidepressant effects for treatment-resistant depression by blocking NMDA receptors, which triggers glutamatergic signaling that promotes synaptic plasticity and neurogenesis. This review synthesizes preclinical and clinical evidence on how these neuroplastic changes unfold over hours to days, linking molecular mechanisms like BDNF signaling and mTOR pathway activation to improvements in mood, motivation, cognition, and functional outcomes. It emphasizes the temporal trajectory of ketamine's effects and offers a plasticity-centered model to integrate neuroscience with clinical psychiatry, while identifying gaps in translational research for optimizing fast-acting antidepressants.

DOI: 10.1007/s40261-026-01565-9 (opens in new tab) Full text (opens in new tab)

From psychache to neuroplasticity: A unified rescue-repair model of Ketamine's anti-suicidal action.

Neurosci Biobehav Rev June 7, 2026 Yoav Domany, Aviv Solomon-Shashua

Suicidality, driven by unbearable psychological pain, is a uniquely human experience increasingly recognized as partly separable from depression in neurobiology and treatment response. Ketamine produces rapid reductions in suicidal ideation that precede and are partly separable from its antidepressant effects. The proposed Unified Rescue-Repair Model describes a two-phase mechanism: an acute rescue phase within minutes involving glutamatergic surge silencing the lateral habenula and disrupting network connectivity, and a structural repair phase unfolding over hours to days involving adenosine surge restoring neuronal bioenergetics and driving synaptogenesis. The model identifies two candidate phenotypes and proposes three predictions for validation.

DOI: 10.1016/j.neubiorev.2026.106804 (opens in new tab)

Clinical trials

All Neuroplasticity trials →