Skip to content

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.

Confidence in the evidence

Moderate
  • Multiple studies (e.g., article_id 26108, 25663, 25710, 2125) provide convergent evidence for neuroplasticity from meditation and psychedelics, but sample sizes are small (e.g., n=20, n=16).
  • The evidence includes both preclinical and clinical studies, but many clinical studies are open-label (e.g., article_id 15990, 15754, 15745) and lack rigorous blinding.
  • There is consistency in the direction of effects (positive for neuroplasticity), but some studies show mixed or null results (e.g., article_id 27727 shows no effect of microdosing on neurogenesis in rats).
  • The body of evidence includes reviews (e.g., article_id 2404, 16857) that synthesize findings, but the field is still emerging with many unanswered questions about mechanisms and long-term effects.
How we rate confidence

Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.

Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.

Evidence by study

Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.

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 →

1,064 articles · 631 from the last two years · 26,792 participants across 147 studies reporting sample size

Common study designs

review 330 narrative review 46 experimental study 103 observational cohort 43 theoretical or philosophical paper 124

Research

Synthesize the evidence → Search all →

Co-Boost: Boosting and guiding neuroplasticity by combining ketamine with neurofeedback-assisted learning – towards an individualised and integrated pharmaco-psychotherapy for cocaine addiction: study protocol for a randomised, placebo-controlled, double-blind, parallel-group, single-centre trial

Anna Stefania Trippel, Ladina Philomena Gubser, Etna Jennifer Elektra Engeli et al.

A randomized, placebo-controlled, double-blind trial will test a single ketamine infusion, three sessions of reward-imagery real-time fMRI neurofeedback training, and their combination in 120 people with cocaine use disorder. The study expects both interventions to reduce the proportion of cocaine use days, with ketamine increasing glutamate in the reward system and lowering craving, and neurofeedback re-sensitizing participants to natural rewards. This neurobiologically informed approach aims to open new treatment avenues through individualized pharmaco-psychotherapy.

DOI: 10.21203/rs.3.rs-5677691/v1

Improvement in Depressive Symptoms in a Patient with Severe and Enduring Anorexia Nervosa and Comorbid Major Depressive Disorder Using Psychotherapy-Assisted IV Ketamine : A Case Report

Amanda Timek, Catherine Daniels-Brady, Stephen Ferrando

A 33-year-old woman with severe and enduring anorexia nervosa and major depressive disorder, who had not improved with numerous prior treatments including antidepressants, mood stabilizers, antipsychotics, electroconvulsive therapy, and various therapies, received seven sessions of intravenous ketamine combined with acceptance and commitment therapy in a hospital setting. She showed increased cognitive flexibility, disappearance of suicidal ideation, and reduction in Beck Depression Inventory scores. Her body mass index was profoundly low at 13, whereas the lowest previously documented in the literature was 16.9. Ketamine-assisted psychotherapy may be a promising treatment for patients with anorexia nervosa and comorbid depression who have failed other interventions.

DOI: 10.21203/rs.3.rs-3976846/v1

Concurrent Changes in Self-Reported Sleep Disturbance During At-Home Ketamine-Assisted Therapy for Depression: A Retrospective Analysis of 13,963 Adults

Research Square Jack Swain, Davis Carter, Leonardo Vando et al.

Among 13,963 adults with moderate-to-severe sleep disturbances who received at-home ketamine-assisted therapy for depression, 67.4% showed at least a 1-point improvement on a single sleep-related item from a depression screening tool after two sessions. By session six, 76.8% of completers met that threshold, and the average score dropped 48.8% from baseline. However, the study could not separate sleep changes from mood improvement because all participants were treated for depression and no control group was included. Side effects were reported by 3.7% to 5.0% of participants across sessions.

DOI: 10.21203/rs.3.rs-9553669/v1

Mindfulness-Based Psilocybin-Assisted Therapy (MB-PAT) for cancer-related demoralization in Canada: the case for a hybrid group-based delivery model

Christopher P. Albertyn, Jérémie Richard, Ron Joseph Shore et al. preprint

Demoralization syndrome affects about one in five Canadians with advanced cancer, marked by helplessness, hopelessness, and loss of meaning, and is linked to a greater desire for hastened death and worse outcomes, but it is underrecognized and undertreated. Pharmacological treatments fail to address its existential roots, and psychosocial therapies are underfunded and not universally effective. Mindfulness-Based Psilocybin-Assisted Therapy (MB-PAT) combines mindfulness training with psilocybin's neuroplastic effects, but its traditional one-on-one delivery limits scalability. The authors argue that group-based MB-PAT could bridge this gap by leveraging existing group therapy infrastructure and therapist familiarity with mindfulness, offering a scalable, equity-focused model for publicly funded Canadian oncology. The Canadian Network for Psychedelic-Assisted Cancer Therapy (CAN-PACT) is highlighted as a key initiative to generate evidence and capacity.

DOI: 10.31234/osf.io/yrgkf_v1

Case series of psilocybin self-medication for spinal cord injury

SSRN Electronic Journal Robin Sandell, Adele Lafrance, Olivia Gosseries et al.

In three people with incomplete spinal cord injuries who self-medicated with psilocybin, improvements in motor function, muscle activation, and strength were reported. One person with a C4–C5 injury noted better gait automaticity; another with a T7 injury regained activation of a previously non-responsive hamstring muscle; a third with a T12 injury experienced rapid strength gains and enhanced proprioceptive awareness. All three reported psychological benefits such as increased wellbeing, motivation for recovery, and improved adjustment. Benefits appeared greatest in partially innervated muscles and diminished after stopping psilocybin. Temporary spasticity was the only adverse effect. The authors suggest psilocybin may enhance recovery by amplifying existing neural pathways and call for controlled clinical trials.

DOI: 10.2139/ssrn.6718771

Esketamine-induced dentate gyrus plasticity in treatment resistant depression: First-in-human evidence

Research Square Alice Le Berre

In adults with treatment-resistant depression, esketamine was associated with early microstructural changes in the dentate gyrus of the hippocampus: reduced fractional anisotropy and increased orientation dispersion index, consistent with greater dendritic complexity. Lower baseline left-dentate gyrus fractional anisotropy correlated with greater improvement at two weeks, and a decrease in fractional anisotropy over that period also correlated with improvement. These changes suggest esketamine may promote hippocampal plasticity, and baseline diffusion MRI metrics could serve as candidate biomarkers for treatment response. The study included 12 adults with treatment-resistant depression and 24 matched controls, but larger studies are needed.

DOI: 10.21203/rs.3.rs-8196324/v1

Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents

bioRxiv (Cold Spring Harbor Laboratory) Lucas Dwiel, Angela Henricks, Elise Bragg et al. 1 citation preprint

Lysergic acid diethylamide (LSD) acutely reduces low-frequency electrical activity across the brain in rats, an effect that returns to normal after 24 hours. However, brain stimulation applied during a window of heightened neuroplasticity 24 hours after LSD produces larger and distinct changes in brain activity compared to stimulation after a placebo. This proof-of-concept finding suggests that psychedelic drugs may work in combination with brain stimulation to achieve enhanced effects on brain activity, with future work needed to assess impacts on behavior.

DOI: 10.1101/2022.10.31.514588

Classic psychedelics and autism spectrum disorder: preclinical evidence, mechanistic insights and unresolved challenges.

Neuroscience and biobehavioral reviews August 1, 2026 Fabrizio Ascone, Diletta Giangiacomo, Viviana Trezza

A review of preclinical studies finds that classic psychedelics affect behavioral domains overlapping with autism spectrum disorder (ASD), including social interaction, communication, repetitive behaviors, anxiety-like traits, and cognitive function. The neurobiological mechanisms involve serotonergic signaling, glutamatergic neurotransmission, neuroinflammatory processes, BDNF/TrkB pathways, and oxytocinergic and dopaminergic modulation. Mechanistic convergence with neurobiological alterations implicated in ASD is identified, but significant gaps constrain interpretation, including a scarcity of studies in established animal models of ASD, reliance on simplified behavioral assays, and uncertainty about how ASD-specific circuit alterations may influence responses to psychedelics.

DOI: 10.1016/j.neubiorev.2026.106761 Full text Synaptic plasticity 5-ht2a signaling Autism spectrum disorder Classic psychedelics +2

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

Pharmacology, biochemistry, and behavior August 1, 2026 Mengyang He, Zhifei Shi, Ruijie Zhan et al.

Depression involves multiple dysfunctions across brain systems, including emotional-cognitive circuits, stress hormone regulation, neurotransmitter systems, and neuroplasticity. This review argues that the BDNF/CREB signaling pathway acts as a central hub connecting these systems. It explains how genetic variations, stress-related epigenetic changes, and microRNA regulation affect this pathway, which in turn influences brain plasticity, stress toxicity, and neurotransmitter balance. The review also describes how antidepressants like ketamine, rTMS, and SSRIs work by activating this pathway, supporting its potential as a biomarker and treatment target. Limitations and future directions integrating multiomics and neuroimaging are discussed, reconceptualizing depression as a network disorder centered on BDNF/CREB signaling.

DOI: 10.1016/j.pbb.2026.174215 Full text Major depressive disorder Neuroplasticity Bdnf/creb signaling pathway Emotional–cognitive circuit +3

Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus.

Hearing research August 1, 2026 Shuhan Lu, Zhixin Zhang, Xinmiao Xue et al.

Tinnitus, the perception of sound without an external source, lacks effective treatments. Psilocybin, a psychedelic, shows promise by activating 5-HT2A receptors, boosting glutamate release, and upregulating BDNF, which increases dendritic spine density and synaptic proteins in the hippocampus and prefrontal cortex, restoring neural plasticity. This review connects these neuroplasticity mechanisms to tinnitus-related neural changes, highlighting psilocybin's regulatory effects on excitatory (glutamate, dopamine) and inhibitory (GABA) neurotransmitters and their receptors, suggesting a novel therapeutic pathway.

DOI: 10.1016/j.heares.2026.109701 Full text 5-ht2a receptor Psilocybin Dopamine Gaba +2

Clinical trials

All Neuroplasticity trials →