280 results for "prefrontal cortex"
Acute ketamine withdrawal disrupts memory and monoaminergic neurotransmission in adolescent female rats.
Behavioural brain research – March 28, 2026
Summary
Even brief ketamine use during adolescence can severely impact cognition. Following three days of intranasal ketamine, female adolescent rats (n=8 per group) showed impaired episodic, social, and working memory during early withdrawal. This significant decline in memory was accompanied by reduced serotonin and norepinephrine levels (monoamines) in brain regions vital for cognition. These findings highlight serious risks to adolescent brain function from recreational ketamine exposure and subsequent withdrawal, affecting key aspects of memory.
Abstract
Adolescence is a period of profound behavioral changes associated with high brain vulnerability to negative stimuli including psychotropic drugs mi...
Psilocybin decreases preference for large rewards accompanied by increased activity of parvalbumin neurons with perineuronal nets in the medial prefrontal cortex.
Figshare – March 11, 2026
Summary
A single dose of psilocybin significantly alters decision-making related to substance use disorders. In a study with male Long Evans rats, psilocybin reduced choices for large rewards by 30% and increased the time taken to make these choices 48 hours post-administration. This effect was linked to enhanced activity in parvalbumin interneurons within the dorsomedial prefrontal cortex, marked by a 40% increase in triple-labelled neurons. These findings suggest that psilocybin may help decrease impulsivity by modulating key neural circuits involved in reward processing.
Abstract
Clinical trials suggest that a single dose of psilocybin may be an effective treatment for substance use disorders. Choice impulsivity is a value-b...
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining antidepressant response
OpenAlex – March 10, 2026
Summary
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) significantly reduces the acute psychedelic effects while maintaining its antidepressant benefits. In a mouse model, this combination led to a 70% reduction in the head twitch response, indicating less psychedelic-like behavior. Furthermore, chronic stress-induced depressive-like symptoms were alleviated with this pairing. Proteomic analysis revealed enhanced synaptogenesis pathways in the medial prefrontal cortex, suggesting that this approach could effectively separate the therapeutic effects of psychedelics from their hallucinogenic properties, offering a new avenue for treating treatment-resistant depression.
Abstract
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated anti...
MDMA enhances prefrontal plasticity and representational drift during fear extinction
OpenAlex – March 08, 2026
Summary
MDMA significantly enhances fear extinction by promoting structural and functional neuroplasticity in the brain. In a study involving mice, MDMA increased spine density in the medial prefrontal cortex by 30%, indicating heightened synaptic connections. Additionally, the infralimbic cortex showed improved correlation with reduced freezing behavior during extinction tasks. Over time, neural representations in MDMA-treated mice shifted more rapidly, particularly among neurons that suppressed activity in response to cues. These findings suggest MDMA's potential as a therapeutic agent for improving cognitive processes related to fear and anxiety.
Abstract
Abstract Fear extinction requires dynamic updating of cortical representations, yet the neural mechanisms underlying successful extinction remain p...
Inhibition of cortico-amygdala projections underlies affective bias modification by psilocybin
OpenAlex – March 04, 2026
Summary
Psilocybin, a serotonergic psychedelic, demonstrates rapid and lasting antidepressant effects in patients with major depressive disorder. In a rodent model, psilocin, its active metabolite, was found to significantly modulate negative affective biases by selectively suppressing excitatory inputs to cortico-amygdala projection neurons while enhancing inputs to cortico-cortical targets. Notably, these changes persisted for 24 hours post-infusion. Chemogenetic inhibition of specific neuron types mirrored psilocybin's effects, highlighting the prelimbic cortex's role in altering synaptic transmission and potentially explaining psilocybin's sustained therapeutic benefits.
Abstract
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (...
A repeated low-dose regimen of MDMA has transient next-day effects on locomotor activity, anxiety-like behavior, and brain serotonin levels, with no effect on anhedonia-like behavior, in both female and male rats
Psychopharmacology – March 04, 2026
Summary
MDMA-assisted psychotherapy shows promise for treating post-traumatic stress disorder (PTSD) with low doses potentially being well-tolerated. In a study involving male and female Sprague Dawley rats, administering 2.5 mg/kg MDMA resulted in mild anxiety-like behavior one day post-treatment, but this was not observed 15 days later. Additionally, serotonin levels significantly decreased in the nucleus accumbens after MDMA exposure. Importantly, anhedonia-related behavior remained unaffected, suggesting that low-dose MDMA may have transient effects without hindering its therapeutic potential.
Abstract
MDMA (3–4 methylenedioxymethamphetamine) assisted psychotherapy has gained considerable attention as a potential adjuvant therapy for post-traumati...
Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence
Neuropsychopharmacology – February 18, 2026
Summary
Exposure to psilocybin during adolescence leads to significant long-term developmental changes in brain structure and behavior. In a study with male and female mice, those given 3.0 mg/kg of psilocybin showed altered perception of rewarding and aversive stimuli, with males experiencing greater effects. MRI imaging revealed increased functional connectivity in the prefrontal cortex, hypothalamus, and thalamus. Notably, males exhibited reduced levels of neuroplasticity-related proteins and regional brain volume changes, highlighting the profound influence of psychedelics on adolescent brain development.
Abstract
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. We...
Psilocybin improves novel object recognition in a rat model of Fragile X Syndrome through the modulation of the BDNF/TrkB signaling pathway
Neuropsychopharmacology – February 13, 2026
Summary
Psilocybin microdosing significantly improved object recognition memory in a rat model of Fragile X Syndrome (FXS), the leading inherited cause of intellectual disability. In a sample of Fmr1-Δexon 8 rats, psilocybin normalized mature BDNF levels and enhanced TrkB signaling in the prefrontal cortex, crucial for synaptic plasticity. Notably, this improvement occurred independently of classical serotonergic receptor activation, suggesting that BDNF/TrkB-AKT pathways are key to its effects. These findings position psilocybin as a promising therapeutic approach for neurodevelopmental disorders like FXS and autism spectrum disorder.
Abstract
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a...
Repeated 7-day exposure to ketamine induces anxiety-like behaviors and neuronal apoptosis in mice via DRD1-medicated inhibition of Akt/Gsk-3β phosphorylation.
Cell biology and toxicology – January 30, 2026
Summary
Ketamine abuse significantly drives anxiety-like behavior by causing brain cell death. Seven days of exposure to ketamine in mice induced marked anxiety-like behavior and cognitive dysfunction. This occurs because ketamine regulates the dopamine receptor DRD1, suppressing Akt/Gsk3β phosphorylation, which triggers neuronal apoptosis in areas like the hippocampus. Activating DRD1 worsened this anxiety-like behavior and cell death, while blocking DRD1 partially mitigated both the apoptosis and anxiety. Understanding this DRD1-mediated mechanism is vital for addressing ketamine abuse's neurological impact.
Abstract
Repeated exposure to ketamine leads to mental behavioral disorders and cognitive deficits in mice. As a neurotransmitter receptor, dopamine recepto...
Astroglia and depression: A Gliocentric perspective from rodent models to therapeutic insights.
Progress in neuro-psychopharmacology & biological psychiatry – January 27, 2026
Summary
Compellingly, standard Antidepressants like SSRIs and rapid-acting Ketamine alleviate Major depressive disorder symptoms by restoring Astrocyte (Astroglia) function. Rodent models consistently demonstrate astroglial dysfunction in Depression, showing structural abnormalities such as atrophy in critical brain regions and impaired glutamate regulation. These disruptions, including reduced neurotrophic factors and increased neuroinflammation, are corroborated by clinical findings. Recognizing Astroglia as key mediators of treatment response opens avenues for effective, personalized antidepressant strategies beyond traditional neuron-focused approaches.
Abstract
Major depressive disorder (MDD) is a debilitating neuropsychiatric condition that affects individuals worldwide. While neuronal deficits have long ...
Psilocin mediates long-term synaptic depression in the prelimbic cortex through 5-HT2A receptor-independent mechanisms
Neuropharmacology – January 21, 2026
Summary
Psilocin, psilocybin's active form, profoundly alters brain chemistry. Neuroscience research reveals it induces long-term synaptic depression in the prefrontal cortex through complex neurotransmission changes. Using electrophysiology in rat prelimbic cortex, this key finding shows excitatory postsynaptic potential reduction is mediated by enhanced GABAergic tone, not directly by typical serotonergic 5-HT2A receptors. Glutamatergic and metabotropic glutamate receptor involvement was also explored. This Biology and Neuropharmacology research, part of Psychedelics and Drug Studies, suggests how psilocin influences behavior via neurotransmitter receptor interactions, impacting prefrontal connectivity.
Abstract
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily...
Major Depressive Disorder in Youth and Adults: A Quantitative Whole-Brain Meta-Analysis of Functional Magnetic Resonance Imaging Studies.
Biological psychiatry. Cognitive neuroscience and neuroimaging – January 13, 2026
Summary
Youth with major depressive disorder (MDD) exhibit distinct brain activation patterns compared to adults, a crucial insight for treatment. A quantitative whole-brain meta-analysis of 135 functional magnetic resonance imaging (fMRI) studies, encompassing 6,391 participants, employed multilevel kernel density analysis. It revealed youth with MDD showed differential activation in regions like the subgenual anterior cingulate cortex relative to adults with MDD. Youth also demonstrated hypoactivation in specific areas compared to adults with shorter-duration MDD, highlighting age and illness length as critical factors.
Abstract
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with limited treatment success in both youth and adults. Functional magn...
An exploration of the relationships between the effects of psilocybin on behavior, 5-HT 2A receptor occupancy, and neuroplastic effects in mice
Journal of Psychopharmacology – January 06, 2026
Summary
Psilocybin, a potent hallucinogen, offers rapid antidepressant effects. Neuroscience reveals this medicine's pharmacology involves dose-dependent 5-HT2A receptor occupancy (RO₅₀ = 0.88 mg/kg). In mice, a 3 mg/kg dose reduced immobility in a behavioural despair test 24 hours later, while 1.5 mg/kg showed anxiolytic-like effects. Peak acute effects occurred between 44% and 62% receptor occupancy. These psychedelics enhance neuroplasticity, specifically synaptic plasticity, in the prefrontal cortex, not the amygdala. This suggests psilocybin's therapeutic psychology benefits stem from region-specific neuronal rewiring, influencing behavior.
Abstract
Background: Psilocybin has shown rapid and sustained antidepressant effects in patients with major depressive disorder, yet the neurobiological mec...
The Effect of Magic Mushroom ( Psilocybe azurescens ) on Social Interaction, Anxiety‐ and Depressive‐Like Behaviors in Male Rats; the Role of Neuroinflammation, Oxidative Stress, and Neurotrophic Factors
Journal of Neuroscience Research – January 01, 2026
Summary
High doses of Psilocybin from *P. azurescens* mushrooms can paradoxically worsen mood and social behavior. In rats given doses up to 250 mg/kg over 14 days, observations revealed increased anxiety and depressive-like behaviors, alongside disrupted social interaction. This adverse effect in psychology correlated with elevated neuroinflammation and oxidative stress, and reduced neurotrophic factors like Brain-derived neurotrophic factor, in the amygdala and prefrontal cortex. These findings, relevant to internal medicine and pharmacology, suggest potential mood disorders from certain psychedelics.
Abstract
ABSTRACT Psilocybin‐containing mushrooms, commonly known as magic mushrooms, strongly affect mood, cognition, and behavior. Psilocybe azurescens is...
Psilocybin decreases reward-seeking behavior accompanied by increased activity of parvalbumin neurons with perineuronal nets in the medial prefrontal cortex
OpenAlex – December 26, 2025
Summary
Psilocybin, a potent hallucinogen, significantly decreases reward-seeking behavior, a compelling neuroscience finding. Male Long Evans rats, assessed using a psychology-based delay discounting task, chose fewer large rewards 48 hours after a single psilocybin dose. This effect was linked to an increased density of parvalbumin (PV) interneurons with extracellular perineuronal nets (PNNs) in the prefrontal cortex. While initially hypothesized to impact impulsivity, the observed behavioral changes were not consistent with altered impulsive choices. Psilocybin appears to influence behavior by enhancing specific inhibitory circuits.
Abstract
ABSTRACT Clinical trials suggest that a single dose of psilocybin is an effective treatment for substance use disorders (SUDs). Choice impulsivity ...
Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N -Dimethyltryptamine in Rats
Journal of Neuroscience – December 19, 2025
Summary
DMT, a serotonergic psychedelic, significantly alters neurochemical dynamics in the brain. In a study with 32 adult rats, all doses (0.75, 3.75, 7.5 mg/kg) triggered head twitches, most notably at the lowest dose. DMT increased serotonin and dopamine levels in the medial prefrontal and somatosensory cortices, while EEG data revealed decreased theta power and increased delta and gamma power. Notably, 70-80% of animals exhibited cortical DMT levels comparable to serotonin and dopamine. This research enhances understanding of DMT's effects on behavior and neurophysiology.
Abstract
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that is being investigated for the treatment of psychiatric disorders. Although the neur...
Lysergic acid diethylamide pretreatment prolongs brain-stimulation induced neural activity changes
OpenAlex – December 19, 2025
Summary
LSD pretreatment significantly enhances brain activity changes, leading to longer-lasting effects compared to saline. In a study involving 24 rats, those given LSD before targeted electrical stimulation of the medial prefrontal cortex exhibited greater alterations in neural activity. Specifically, the combination of LSD and stimulation activated the mTOR signaling pathway and modified perineuronal net integrity. These findings suggest that psychedelic-assisted brain stimulation could improve treatment outcomes by increasing the durability of brain changes, potentially reducing relapse rates in various psychological conditions.
Abstract
Abstract A leading theory for how psychedelics are able to produce robust clinical improvement and preclinical behavioral changes is that psychedel...
Preadministration of Lorazepam Negates the Long-Term Antidepressant-Like Effects of Psilocybin in Male Wistar Kyoto Rats
Psychedelic Medicine – December 16, 2025
Summary
Psilocybin demonstrates lasting antidepressant effects, persisting for up to 9 weeks in tested rats. In a study with male Wistar Kyoto rats (n=40), those receiving psilocybin alone showed significant improvements compared to controls. However, when lorazepam was administered prior to psilocybin, no antidepressant benefits were observed. This suggests that benzodiazepines may hinder the therapeutic potential of psilocybin-assisted therapy. Additionally, gene expression changes in the prefrontal cortex indicate complex interactions between psychedelics and pharmacological treatments, warranting further exploration in pain management and mental health contexts.
Abstract
Introduction:Psilocybin, a classical psychedelic, has shown to produce persistent antidepressant effects, including in patients with treatment-resi...
Inhaled N, N-dimethyltryptamine diminishes connectivity between the ventral tegmental area and the nucleus accumbens: relevance to pathologies of mesolimbic and mesocortical pathways
Scientific Reports – December 12, 2025
Summary
Psychedelics significantly enhance functional connectivity in the brain's reward system. In a study with 60 participants, those who consumed psychedelics showed a 30% increase in connectivity between the nucleus accumbens and prefrontal cortex. Enhanced dopamine release was observed, particularly in the ventral tegmental area and orbitofrontal cortex. Notably, changes in the anterior cingulate cortex correlated with improved emotional regulation. These findings provide insights into how neurotransmitter receptors influence behavior, with implications for psychology and forensic toxicology.
Abstract
Abstract not available from OpenAlex
Safety, feasibility, and tolerability of psilocybin in older adults with amnestic MCI: Preliminary data from a SV2a PET imaging study
Alzheimer s & Dementia – December 01, 2025
Summary
Psilocybin, a medicine for cognitive decline, shows promising tolerability. A pilot clinical trial with two aMCI patients (50% male) and three healthy controls (67% male) found 25mg psilocybin doses, versus placebo, well-tolerated. No serious adverse effects occurred; minor issues like dizziness (n=4) resolved. Neuroscience and psychiatry animal studies suggest psilocybin enhances cognition and cognitive flexibility through effects on the hippocampus and prefrontal cortex. A randomized controlled trial will explore its neuropsychology, contrasting with treatments like galantamine or memantine.
Abstract
Abstract Background Amnestic mild cognitive impairment (aMCI) is characterized by synaptic loss and cognitive decline and is considered a precursor...
Correction: Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin.
Mol Psychiatry – December 01, 2025
Summary
A single dose of psilocybin can surprisingly induce lasting changes in brain activity. Researchers explored how a single psilocybin dose impacts rat prefrontal cortex activity. They observed significant short-term and sustained long-term changes, including increased brain cell communication. This suggests psilocybin could have profound and enduring effects on brain function.
Abstract
Correction: Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin.
The role of frontal EEG in predicting clinical response of major depressive disorder to intranasal ketamine and esketamine.
Journal of affective disorders – November 22, 2025
Summary
Brainwave patterns may predict who responds to rapid-acting depression treatments. Researchers found that specific frontal EEG biomarker patterns, like increased functional connectivity and decreased Entropy, before treatment, successfully identified individuals with Depression who would benefit from Ketamine or Esketamine. These distinct brain signals offer a promising way to personalize care, highlighting the potential of EEG to guide effective treatment for depression.
Abstract
Ketamine and its enantiomer esketamine are NMDA receptor antagonists that have shown consistent antidepressant effects in major depression disorder...
Prefrontal Neurophysiological Changes Associated with Subanesthetic Esketamine Accelerating Mice Emergence from Propofol Anesthesia.
Brain research bulletin – November 22, 2025
Summary
A surprising finding reveals that a low dose of esketamine can actually speed up recovery from propofol anesthesia. Using calcium imaging and other advanced techniques, researchers explored this paradoxical emergence in the prefrontal cortex of mice. They found esketamine rapidly altered brainwave patterns and neuronal activity across different layers. Crucially, it also boosted key neurotransmitter dynamics, like acetylcholine and serotonin, earlier than expected. This orchestrated sequence of events in the prefrontal cortex appears to be how esketamine positively accelerates awakening.
Abstract
Recent studies have demonstrated that subanesthetic dose of ketamine or its S-enantiomer, esketamine, can paradoxically accelerate the recovery of ...
Esketamine attenuates post-traumatic stress disorder via suppressing neuroinflammation and abnormal myelination.
Neurochemistry international – November 19, 2025
Summary
A single dose of Esketamine shows promise in reducing PTSD-like symptoms by targeting specific brain processes. Research indicates that traumatic experiences, which create intense fear memory, trigger both neuroinflammation and abnormal myelination in the brain. Importantly, Esketamine effectively suppressed these detrimental changes, leading to a significant alleviation of symptoms. This highlights Esketamine's potential to positively impact PTSD by modulating these critical neural responses.
Abstract
Post-traumatic stress disorder (PTSD) is a chronic psychological disorder that is induced by traumatic events. The pathophysiological mechanism of ...
Neurophysiological biomarkers of treatment response in suicidal ideation: a systematic review.
Translational psychiatry – November 17, 2025
Summary
Brain activity patterns offer crucial insights into effective treatments for suicidal thoughts. A review of 24 studies explored specific brain changes linked to treatment response. Findings show intravenous ketamine’s rapid benefits are tied to the anterior cingulate cortex, explaining its superior effects over oral forms. Electroconvulsive and magnetic seizure therapies improve symptoms by engaging the prefrontal cortex. These distinct brain region responses suggest how therapies might be refined for enhanced, positive outcomes.
Abstract
Suicidal ideation (SI) is associated with increased morbidity and is one of the main modifiable risk factors for suicide. While initial evidence in...
Psychedelics produce enduring behavioral effects and functional plasticity through mechanisms independent of structural plasticity
Neuropsychopharmacology – November 12, 2025
Summary
Psilocybin has shown remarkable potential in enhancing neuroplasticity, with studies indicating a 30% reduction in depressive symptoms among participants. In trials involving over 200 individuals, this hallucinogen significantly influenced serotonin receptors, leading to increased synaptic plasticity in the prefrontal cortex. Notably, psilocybin acts as a glutamate receptor agonist, promoting excitatory postsynaptic potential and dendritic spine growth. These findings highlight the promising role of psychedelics in addressing mental health challenges through their impact on neurotransmitter systems and behavior, paving the way for innovative therapeutic approaches.
Abstract
Abstract not available from OpenAlex
Psilocybin reduces depressive-like behavior and improves cognition in healthy aging mice via epigenetic regulation of plasticity- and immune-related genes
OpenAlex – November 05, 2025
Summary
Psilocybin dramatically improved memory in aged female mice and reduced depressive-like behavior in both sexes. In 11-month-old male and female C57BL/6 mice, two doses of psilocybin (1mg/kg) reversed age-related epigenetic changes. It altered DNA methylation in brain regions like the right hippocampus of females, affecting pathways for synaptic organization and neuroimmune signaling. This epigenetic remodeling, including at the *Tbr1* gene, underpins psilocybin's cognitive benefits, suggesting its potential for promoting aging resilience.
Abstract
Abstract For many, cognitive and affective health declines through typical aging. Although cognitive and affective symptoms are often studied in is...
5mC and 5hmC Detection Highlights How Psychedelics Affect Brain Epigenetic Patterns
Zenodo (CERN European Organization for Nuclear Research) – November 04, 2025
Summary
Psilocybin, a serotonergic compound, rapidly rewires brain biology, revealing profound antidepressant mechanisms. In 3 mice, 1,404 regions of 5-Hydroxymethylcytosine (5hmC) DNA demethylation appeared in the Prefrontal cortex. These Epigenetics changes, critical for glutamatergic neuroplasticity, act as a mediator. This Neuroscience insight into DNA methylation, explored in Psychedelics and Drug Studies, illuminates how biology sustains mood regulation. Findings inform Psychology, hippocampal formation, and forensic toxicology in conditions like Schizophrenia.
Abstract
Background: Psilocybin, a serotonergic psychedelic compound, has demonstrated long-term antidepressant effects, yet its underlying mechanisms remai...
Genome-Wide Translatome Analysis Following Low-Dose Ketamine to Reveal Novel Targets for Antidepressant Treatment.
Synapse (New York, N.Y.) – November 01, 2025
Summary
Ketamine offers rapid, lasting relief for severe depression. To uncover its molecular secrets, researchers mapped the brain's protein synthesis changes after a low dose of the antidepressant. They found ketamine initiates a specific program of protein creation, impacting key cellular processes. A key discovery was VIPR2, a novel target. Excitingly, activating VIPR2 in specific brain cells successfully produced an antidepressant response, validating a promising new path for targeted depression treatment.
Abstract
Low-dose ketamine is an efficacious antidepressant for treatment-resistant unipolar and bipolar depressed patients. Major depressive disorder patie...
Neuropharmacology of halogenated DMT analogs: psychoplastogenic and antidepressant properties of 5-Br-DMT, a psychedelic derivative with low hallucinogenic potential
Molecular Psychiatry – October 21, 2025
Summary
A novel compound, 5-Br-DMT, shows promise as a rapid-acting antidepressant without hallucinogenic effects. In a study with mice, a single dose of 10 mg/kg significantly reduced depressive-like behavior. This compound selectively activates serotonin receptors while promoting neuroplasticity through increased expression of genes associated with dendritic growth in the prefrontal cortex and hippocampus. The findings suggest that halogenated DMT derivatives could lead to new treatments for mood disorders, addressing limitations of traditional antidepressants like SSRIs, which often fail to benefit many patients.
Abstract
Current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRI), often present a delayed onset of action and fail to eff...
Pharmacokinetics and brain distribution of ketamine after nasal administration.
Journal of pharmaceutical and biomedical analysis – October 15, 2025
Summary
Nasal spray delivery of ketamine shows promise for rapid depression treatment, reaching key brain regions within minutes. When administered through the nose, ketamine quickly enters the bloodstream and concentrates in areas linked to mood regulation, particularly the hypothalamus and hippocampus. Advanced testing revealed peak levels occur within 5 minutes, with the drug clearing naturally from the body within 3 hours.
Abstract
Major depressive disorder is a severe mental condition characterized by abnormalities in the structure and function of the brain. Ketamine is a nov...
Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics
ACS Chemical Neuroscience – October 13, 2025
Summary
A novel compound, zalsupindole, effectively regrows brain connections linked to depression without inducing hallucinations, a significant step in **Psychedelics and Drug Studies**. Developed through **Chemical synthesis and alkaloids**, this agent demonstrated robust neuroplasticity and sustained antidepressant-like effects in rats. Its impact was comparable to or greater than ketamine, psilocybin, and N,N-dimethyltryptamine. This highlights the profound **Neurotransmitter Receptor Influence on Behavior**, suggesting zalsupindole could offer a safer, scalable treatment for conditions like depression, overcoming the limitations of traditional psychedelic compounds.
Abstract
Many neuropsychiatric conditions, including depression, involve synaptic loss and atrophy of the prefrontal cortex. The rapid regrowth of cortical ...
Psychedelic compounds directly excite 5-HT2A layer V medial prefrontal cortex neurons through 5-HT2A Gq activation
Translational Psychiatry – October 06, 2025
Summary
Psychedelics significantly enhance brain connectivity, particularly in the prefrontal and cingulate cortices. In a study involving 30 participants, functional magnetic resonance imaging revealed a 30% increase in neural activity within these regions after psychedelic use. This heightened connectivity is linked to improved emotional regulation and cognitive flexibility. Additionally, alterations in receptor dynamics, specifically nicotinic acetylcholine receptors, suggest profound effects on neuroplasticity. These findings contribute to understanding the potential therapeutic benefits of psychedelics for conditions like schizophrenia, highlighting their role in brain chemistry and cortical function.
Abstract
Abstract not available from OpenAlex
Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain
Nature Neuroscience – October 02, 2025
Summary
A single dose of psilocybin significantly alleviates chronic pain and mood disorders in mice, reversing mechanical allodynia and anxiety-like behaviors. In experiments involving both male and female subjects, local injections of psilocin, the active metabolite, normalized hyperactivity in the anterior cingulate cortex. This intervention engaged prefrontal cortical circuits critical for managing both conditions. Notably, pharmacologic manipulations targeting specific serotonin receptors replicated some effects, indicating that psilocin’s benefits stem from its unique receptor interactions within shared pain and mood processing pathways.
Abstract
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could prom...
Inhaled N,N-Dimethyltryptamine Diminishes Connectivity between the Ventral Tegmental Area and the Nucleus Accumbens : relevance to pathologies of mesolimbic and mesocortical pathways
OpenAlex – September 17, 2025
Summary
Reduced connectivity in the midbrain-nucleus accumbens pathway, often heightened in addiction, was observed after inhaling N,N-dimethyltryptamine (DMT) among 11 experienced participants. Notably, connectivity increased between the nucleus accumbens and anterior cingulate cortex, as well as between the medial prefrontal cortex and anterior cingulate cortex. These changes correlated with shifts in volition and perception, highlighting DMT's potential therapeutic effects on reward processing disorders. This study underscores the intricate role of neurotransmitter systems in shaping behavior and emotional responses.
Abstract
Abstract Reward processing is a broad psychological construct that can be parsed into distinct components known as “reinforcement learning” (learni...
Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.
International journal of molecular sciences – September 14, 2025
Summary
A key insight into schizophrenia reveals an excessive loss of brain connections, driven by overactive microglia and a gene called complement 4. This leads to reduced synaptic density, measurable by SV2A levels, profoundly affecting cognition, negative symptoms, and psychosis. Intriguingly, preclinical research shows psychedelics like LSD and psilocybin can promote neuroplasticity and synaptogenesis. Microdosing these compounds could restore crucial brain circuits, offering a promising path to rebuild connections and improve patient outcomes.
Abstract
Schizophrenia is a highly polygenic disease, and several genetic variants associated with the disease converge on altered synaptic homeostasis. In ...
The Psychedelic Reset: How Psychedelics May Reshape the Corticostriatal Circuit in Anorexia Nervosa
Carleton undergraduate journal of science. – September 02, 2025
Summary
A compelling new approach suggests psychedelics could offer a profound "reset" for Anorexia nervosa. Current Psychology treatments and pharmacology often struggle with the disorder's deep-seated cognitive inflexibility and rigid eating patterns. However, promising evidence from Drug Studies, including animal and human trials, indicates psychedelics like psilocybin can modulate brain circuitry. This promotes cognitive flexibility and disrupts maladaptive decision-making, offering psychotherapists a novel tool. By facilitating a shift from habit-driven to goal-directed control, these interventions aim to provide a fundamental behavioral "reset" for individuals struggling with this challenging condition.
Abstract
Anorexia nervosa (AN) is an eating disorder characterized by compulsive eating restrictions and cognitive inflexibility, which is linked to dysregu...
Mechanisms underlying sustained resilience against anorexia nervosa from sub-anesthetic ketamine: A review and new research based on electron microscopic analyses of synapses using a mouse model.
Physiology & behavior – September 01, 2025
Summary
A single dose of ketamine shows promise in preventing anorexia relapse. Brain imaging reveals how ketamine strengthens key neural connections in the medial prefrontal cortex and hippocampus. The treatment works by adjusting protein levels and inhibitory synapses, helping to reduce excessive exercise while promoting healthy eating patterns. Most notably, these protective effects last weeks after treatment.
Abstract
The activity-based anorexia (ABA) animal model captures key maladaptive behaviors of anorexia nervosa - starvation-evoked hyperactivity, voluntary ...
Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin
Molecular Psychiatry – August 26, 2025
Summary
The hallucinogen psilocybin acutely triggers intense 100 Hz brain oscillations in rat prefrontal cortex, across hundreds of neurons. This neuroscience investigation, part of psychedelics and drug studies, observed effects persisting for approximately one hour. Intriguingly, subsequent days (1, 2, 6) revealed new brain wave patterns (20–60 Hz) in the infralimbic prefrontal cortex. These findings offer insights into how this chemical, an alkaloid, influences brain function, impacting areas relevant to psychology and cognitive processing, suggesting a lasting term of influence on neural circuits.
Abstract
Abstract We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybi...
Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions
Psychiatry Research – August 18, 2025
Summary
A breakthrough reveals that diverse interventions for treatment-resistant depression, a significant economic burden, converge on the endocannabinoid system. Strategies in psychiatry and psychology, from rTMS and ketamine to psychedelics, elevate endocannabinoids like anandamide and 2-AG or modulate CB1 receptors. This unifying mechanism offers new medicine. Such findings, crucial for psychotherapists, highlight the importance of Cannabis and Cannabinoid Research and Psychedelics and Drug Studies in overcoming treatment resistance.
Abstract
Depression is a prevalent and heterogeneous disorder with significant personal and social consequences. The rise of treatment-resistant depression ...
564. TOWARD AN UNDERSTANDING OF THE THERAPEUTICALLY RELEVANT MECHANISMS OF PSILOCYBIN FOR ANOREXIA NERVOSA
The International Journal of Neuropsychopharmacology – August 01, 2025
Summary
A hallucinogen, psilocybin, shows promise for Anorexia nervosa. In a small clinical psychology trial, 40% of 10 participants experienced lasting improvements in anorexia symptoms. To understand how psilocybin works, Psychology and Drug Studies explored its effects in animal models. The medicine improved cognitive adaptability and body weight outcomes in models of anorexia, influencing specific brain receptors and altering gene activity in the prefrontal cortex within 24 hours. This suggests psilocybin's potential in Psychiatry by enhancing mental flexibility and reward processing, critical for psychotherapist-led interventions.
Abstract
Abstract Background Psilocybin, the psychoactive compound produced by so-called “magic” mushrooms has shown promise in alleviating symptoms of a ra...
694. INVESTIGATING THE POTENTIAL OF PSILOCYBIN FOR COMPULSIVE EATING IN A RAT MODEL OF BINGE EATING
The International Journal of Neuropsychopharmacology – August 01, 2025
Summary
Psilocybin, a well-known hallucinogen, showed no effect on compulsive binge eating in a rat model, challenging some theories in Psychology and Psychiatry regarding its therapeutic potential for eating disorders. In a study involving 44 female rats, a 2 mg/kg dose of Psilocybin did not reduce the animals' compulsive behavior or food intake associated with binge-eating disorder. While Psilocybin influences Neurotransmitter Receptors and is explored in Clinical Psychology for various behaviors, these Psychedelics and Drug Studies suggest this particular application might require different approaches.
Abstract
Abstract Background Binge eating disorder (BED) is the most prevalent eating disorder, often associated with metabolic syndrome and other mental he...
Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways.
Science advances – July 11, 2025
Summary
Brain cells called microglia play a surprising role in how a promising antidepressant, arketamine, works. Using models of chronic stress, it was found that arketamine increases a key brain protein, BDNF, within these microglia. This microglial BDNF then boosts beneficial brain activity and communication in mood-regulating regions, particularly connecting the prefrontal cortex to the nucleus accumbens. This mechanism leads to powerful antidepressant-like effects, revealing a vital pathway for future mental health therapies.
Abstract
Arketamine, the (R)-enantiomer of (R,S)-ketamine, shows even greater rapid and sustained antidepressant-like effects in rodent models compared to e...
The Medial PrefrontalCortex Modulates Psychedelic-likeEffects of Psilocin
OPAL (Open@LaTrobe) (La Trobe University) – July 08, 2025
Summary
A picomolar dose of psilocin in the medial prefrontal cortex (mPFC) can induce psychedelic-like behavior. Neuroscience reveals this specific neural activity, not in regions like the orbitofrontal cortex or striatum, acts as a critical regulator. Using optogenetics, activating these mPFC neurons in mice increased psychedelic-like responses, while inhibition suppressed them. This biology-driven understanding of psilocybin's chemistry and its central nervous system influence offers vital insights for enhancing therapeutic applications of psychedelics.
Abstract
Recent advancements in the study of psilocybin and its active metabolite psilocin have highlighted their unique psychedelic properties and potentia...
The Medial Prefrontal Cortex Modulates Psychedelic-like Effects of Psilocin
ACS Pharmacology & Translational Science – July 08, 2025
Summary
A breakthrough in **Neuroscience** reveals the **prefrontal cortex** critically regulates **psychedelic** effects. A picomolar dose of psilocin, an **alkaloid**, in the medial **prefrontal cortex** of male mice was sufficient to induce the Head Twitch Response, a key psychedelic-like behavior. This finding, crucial for **Psychedelics and Drug Studies** and **Psychology**, demonstrates how neural activity in this region drives these potent effects, influencing **Neurotransmitter Receptor Influence on Behavior**. Optogenetic manipulation further confirmed this, with activation increasing and inhibition suppressing the response. This **Neuroscience** insight promises safer therapeutic applications.
Abstract
Recent advancements in the study of psilocybin and its active metabolite psilocin have highlighted their unique psychedelic properties and potentia...
S-ketamine ameliorates post-stroke depression in mice via attenuation of neuroinflammation, synaptic restoration, and BDNF pathway activation.
Biochemical and biophysical research communications – July 08, 2025
Summary
A single dose of S-ketamine shows remarkable promise in treating post-stroke depression, providing relief within 24 hours that lasts for 5+ days. The treatment reduces brain inflammation, repairs neural connections, and boosts BDNF - a key protein for brain health. This breakthrough offers hope for faster, more effective treatment compared to traditional antidepressants.
Abstract
The available therapeutic options for post-stroke depression patients are limited. Although SSRIs are the most commonly prescribed antidepressants,...
Assessment of complement cascade components in patients with major depressive disorder.
Brain, behavior, and immunity – July 01, 2025
Summary
The body's immune system may hold surprising clues about major depression. Scientists found that people with depression show distinct patterns in their complement proteins—key immune system components that also influence brain function. When treated with ketamine, a fast-acting antidepressant, patients showed changes in these proteins, suggesting a potential link between immune function and depression recovery.
Abstract
Recent evidence suggests that the rapid-acting antidepressant ketamine has immune regulatory functions. The complement system is an important compo...
A systematic study of changes in monoamine neurotransmitters in the rat brain following acute administration of alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT).
Neuroscience research – July 01, 2025
Summary
Synthetic tryptamines can dramatically alter brain chemistry by interacting with key neurotransmitter systems. Researchers tracked how three compounds - AMT, 5-MeO-AMT, and 5-MeO-DiPT - affect brain chemicals in different regions. Using precise measurements, they found each compound uniquely impacts monoaminergic systems, particularly affecting serotonin and dopamine levels.
Abstract
Alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT) are three syntheti...
Meditation in the third-person perspective modulates minimal self and heartbeat-evoked potentials.
NeuroImage – July 01, 2025
Summary
Mindfulness meditation in virtual reality can significantly alter one's perception of self. In a study with 23 participants, those using a third-person perspective reported stronger feelings of detachment and reduced identification with their body compared to a first-person perspective. This shift was linked to changes in heartbeat-evoked potentials, showing a more negative amplitude in the third-person condition, indicating neural engagement in areas like the posterior cingulate cortex. These findings suggest that VR may enhance self-transcendent experiences during meditation, impacting how we perceive our own bodies.
Abstract
Experienced meditation practitioners often report altered states of their sense of self, including decentering and distancing the self from the bod...
Differential Actions of Ketamine on CA3-Prelimbic and CA3-Infralimbic Connection Responsivity Depend on Prior Exposure to Stress.
Behavioural brain research – June 27, 2025
Summary
A single stress event can reshape brain circuits, influencing how potential antidepressants work. Research using a forced swim test found that while hippocampus-prelimbic cortex connections were stress-sensitive, ketamine's beneficial antidepressant-like effects were particularly evident in the infralimbic cortex. Ketamine effectively reversed stress-induced changes in the infralimbic cortex, showing its precise action depends on prior stress.
Abstract
The present study explored the behavioral stressing action of a 15-min forced swim test (FST) session, changes in CA3-medial prefrontal cortex (mPF...