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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.

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

observational · Sample size: 20

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 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

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

preclinical

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

preclinical

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

observational

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

RCT · Sample size: 19

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

review

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

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

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

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

observational

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

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

observational · Sample size: 36

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

preclinical

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

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

preclinical

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

review

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

preclinical

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

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.

926 articles · 558 from the last two years · 24,165 participants across 125 studies reporting sample size

Common study designs

review 280 narrative review 44 experimental study 92 observational cohort 36 theoretical or philosophical paper 92

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.

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, Jeremie 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.

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.

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.

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.

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.

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.

Continuity of matter as the basis of information resonance: a hypothesis on the transmission of experience through atoms in the biological cycle.

Zenodo (CERN European Organization for Nuclear Research) • July 13, 2026 • Vladlena Mayorova

Atoms from a dead organism re-enter the global biogeochemical cycle and may carry an informational resonance—a trace of the previous host's physiological, emotional, and cognitive states. When these atoms are incorporated into a new organism during early development, this resonance could shape behavioral patterns, sensory preferences, emotional reactions, and unexplained phobias. The hypothesis draws on the conservation of mass, epigenetics, quantum entanglement, and over 2,500 documented cases of children's past-life memories. A thought experiment, the 'Girl from 1900,' illustrates the proposed atomic transmission. The paper suggests experimental tests, including epidemiological studies and isotopic labeling in animals, but does not claim proof.

Enhancing plasticity to treat depression and other central nervous system diseases using event-driven pharmacology.

Journal of psychopharmacology (Oxford, England) • July 13, 2026 • Todd D Gould, Sanjay J Mathew, Maurizio Fava et al.

A new pharmacological model called event-driven pharmacology (EDP) is described, in which a plastogen—a drug that induces lasting neural plasticity—produces sustained effects after only transient binding, unlike traditional drugs that require continuous receptor occupancy. Plastogens such as ketamine and classical psychedelics can trigger metaplasticity, priming synapses to respond to later stimuli long after the drug has left the body. Dosing such drugs to maintain constant target occupancy may paradoxically reduce benefits and increase side effects. The EDP model calls for new drug development, dosing strategies, and biomarkers to harness the therapeutic potential of plastogens for depression and other synaptic disorders.

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

Translational Psychiatry • July 11, 2026 • Moira G. Semple, Sarah E. Mennenga, Ryan Smith et al.

Ketamine and MDMA, compounds known as psychoplastogens, show therapeutic potential for mood and trauma-related disorders, but their molecular mechanisms are not fully understood. In a study analyzing blood samples from 20 ketamine-treated participants and saliva samples from 16 MDMA-treated participants, DNA methylation changes were examined using a Brain-Epigenome-Wide Association Study targeting brain-relevant genes. Ketamine was associated with 405 significantly altered genes and 169 functional networks, while MDMA was linked to 346 altered genes and 183 networks. Both compounds converged on pathways related to neuroplasticity and neuroimmune regulation, suggesting they induce peripheral epigenetic changes that engage molecular pathways relevant to psychiatric health.

Clinical trials

All Neuroplasticity trials →