Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025)
Introduction: Substance use disorder (SUD) is a complex neurobiological disorder characterized by the consolidation of maladaptive neuroplasticity affecting dopaminergic, glutamatergic, and neurotrophic systems, as well as cortical and subcortical networks critical for executive control, emotional r...
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2026
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| author | Roberto Estrada-Medina Berle Estalin Briones-Llamoctanta Josue Edison Turpo-Chaparro |
| author_browse | Berle Estalin Briones-Llamoctanta Josue Edison Turpo-Chaparro Roberto Estrada-Medina |
| author_facet | Roberto Estrada-Medina Berle Estalin Briones-Llamoctanta Josue Edison Turpo-Chaparro |
| author_sort | Roberto Estrada-Medina |
| collection | Producción científica |
| description | Introduction: Substance use disorder (SUD) is a complex neurobiological disorder characterized by the consolidation of maladaptive neuroplasticity affecting dopaminergic, glutamatergic, and neurotrophic systems, as well as cortical and subcortical networks critical for executive control, emotional regulation, and associative learning. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines and integrated 57 studies published between 2020 and 2025 to analyze neuroplastic mechanisms involved in vulnerability to substance use disorder and brain recovery following chronic substance exposure. Results: The findings revealed consistent alterations in synaptic density, BDNF/TrkB signaling, glutamatergic homeostasis, and epigenetic regulation, along with structural and functional neuroimaging changes in regions such as the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala. Four core therapeutic domains for neuroplastic restoration were identified: neuromodulation approaches (including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation), compounds that promote neuroplasticity via neurotrophic signaling, epigenetic and anti-inflammatory interventions, and psychological therapies based on memory reconsolidation processes. These strategies demonstrated the capacity to normalize prefrontal activity, modulate reward networks, strengthen emotional regulation, and reduce craving. Conclusion: Despite significant advances, important gaps remain, including methodological heterogeneity, scarcity of longitudinal studies, and limited clinical generalizability. Overall, the evidence suggests that recovery from substance use disorder requires multimodal interventions simultaneously targeting molecular, synaptic, and circuit-level plasticity, with growing emphasis on personalized approaches guided by neurobiological biomarkers. |
| format | Review |
| id | openalex:W7131638333 |
| institution | UPeU |
| language | English |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| record_format | dspace |
| spelling | openalex:W7131638333Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025)Roberto Estrada-MedinaBerle Estalin Briones-LlamoctantaJosue Edison Turpo-Chaparrosubstance use disordersneuroplasticitybrain recoverysynaptic plasticityBDNF/TrkB signalingepigenetic regulationprefrontal cortexnucleus accumbensamygdalaneuromodulationrepetitive transcranial magnetic stimulationtranscranial direct current stimulationdeep brain stimulationmemory reconsolidationcravingneurotrophic signalinganti-inflammatory therapyneurobiological biomarkersNeurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesNeuroscience and Neuropharmacology ResearchIntroduction: Substance use disorder (SUD) is a complex neurobiological disorder characterized by the consolidation of maladaptive neuroplasticity affecting dopaminergic, glutamatergic, and neurotrophic systems, as well as cortical and subcortical networks critical for executive control, emotional regulation, and associative learning. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines and integrated 57 studies published between 2020 and 2025 to analyze neuroplastic mechanisms involved in vulnerability to substance use disorder and brain recovery following chronic substance exposure. Results: The findings revealed consistent alterations in synaptic density, BDNF/TrkB signaling, glutamatergic homeostasis, and epigenetic regulation, along with structural and functional neuroimaging changes in regions such as the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala. Four core therapeutic domains for neuroplastic restoration were identified: neuromodulation approaches (including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation), compounds that promote neuroplasticity via neurotrophic signaling, epigenetic and anti-inflammatory interventions, and psychological therapies based on memory reconsolidation processes. These strategies demonstrated the capacity to normalize prefrontal activity, modulate reward networks, strengthen emotional regulation, and reduce craving. Conclusion: Despite significant advances, important gaps remain, including methodological heterogeneity, scarcity of longitudinal studies, and limited clinical generalizability. Overall, the evidence suggests that recovery from substance use disorder requires multimodal interventions simultaneously targeting molecular, synaptic, and circuit-level plasticity, with growing emphasis on personalized approaches guided by neurobiological biomarkers.Reviewhttps://doi.org/10.3389/fnmol.2026.1760387https://public-pages-files-2025.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2026.1760387/pdfW7131638333enFrontiers in Molecular Neuroscience1662-50992026-02-26 |
| spellingShingle | substance use disorders neuroplasticity brain recovery synaptic plasticity BDNF/TrkB signaling epigenetic regulation prefrontal cortex nucleus accumbens amygdala neuromodulation repetitive transcranial magnetic stimulation transcranial direct current stimulation deep brain stimulation memory reconsolidation craving neurotrophic signaling anti-inflammatory therapy neurobiological biomarkers Neurotransmitter Receptor Influence on Behavior Substance Abuse Treatment and Outcomes Neuroscience and Neuropharmacology Research Roberto Estrada-Medina Berle Estalin Briones-Llamoctanta Josue Edison Turpo-Chaparro Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025) |
| title | Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025) |
| title_full | Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025) |
| title_fullStr | Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025) |
| title_full_unstemmed | Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025) |
| title_short | Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020–2025) |
| title_sort | neuroplasticity and recovery of the brain affected by substance use disorder multilevel mechanisms and new therapeutic strategies 2020 2025 |
| topic | substance use disorders neuroplasticity brain recovery synaptic plasticity BDNF/TrkB signaling epigenetic regulation prefrontal cortex nucleus accumbens amygdala neuromodulation repetitive transcranial magnetic stimulation transcranial direct current stimulation deep brain stimulation memory reconsolidation craving neurotrophic signaling anti-inflammatory therapy neurobiological biomarkers Neurotransmitter Receptor Influence on Behavior Substance Abuse Treatment and Outcomes Neuroscience and Neuropharmacology Research |
| topic_facet | substance use disorders neuroplasticity brain recovery synaptic plasticity BDNF/TrkB signaling epigenetic regulation prefrontal cortex nucleus accumbens amygdala neuromodulation repetitive transcranial magnetic stimulation transcranial direct current stimulation deep brain stimulation memory reconsolidation craving neurotrophic signaling anti-inflammatory therapy neurobiological biomarkers Neurotransmitter Receptor Influence on Behavior Substance Abuse Treatment and Outcomes Neuroscience and Neuropharmacology Research |
| url | https://doi.org/10.3389/fnmol.2026.1760387 https://public-pages-files-2025.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2026.1760387/pdf |
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