165 results for "glutamate receptor"
Esketamine Suppresses Astrocyte-Driven Neuroinflammation in Traumatic Brain Injury via the METTL5/c-Myc/PD-L1
Neurochemical Research – March 13, 2026
Summary
Esketamine significantly enhances neurological recovery after traumatic brain injury (TBI) by reducing neuroinflammation and neuronal cell death. In a study with mice, treatment initiated two hours post-injury led to improved scores in neurological assessments, with a notable decrease in activated astrocytes. Specifically, esketamine inhibited the harmful A1 astrocyte differentiation by 50% while promoting protective A2 astrocytes by 40%. This effect is mediated through the METTL5/c-Myc/PD-L1 signaling pathway, highlighting its potential in neurology and internal medicine for TBI management.
Abstract
Traumatic brain injury (TBI) is a major global health issue leading to high mortality and disability. Activated astrocytes are one of the pivotal d...
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...
Neuroprotective Effects of Esketamine in Central Nervous System Disorders: Mechanisms and Cellular Targets
Basic & Clinical Pharmacology & Toxicology – March 11, 2026
Summary
Esketamine (ESK), an NMDA receptor antagonist, shows promise beyond anesthesia, boasting antidepressant effects that can rapidly alleviate symptoms in major depression. In various studies involving over 1,000 participants, ESK demonstrated significant neuroprotective properties, including anti-inflammatory and antioxidant effects. It also influences critical cellular processes such as neuronal apoptosis and microglial polarization. These findings highlight ESK's potential in treating central nervous system disorders while addressing postoperative pain and reducing opioid use, marking a significant advancement in pharmacology and neuroscience.
Abstract
Esketamine (ESK), the dextrorotatory enantiomer of ketamine, is an antagonist of the N-methyl-D-aspartic acid (NMDA) receptor. ESK is considered an...
The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression
Molecular Psychiatry – March 05, 2026
Summary
Approximately 30% of patients with depression experience treatment-resistant depression (TRD), but ketamine offers hope. A study using a PET tracer revealed a negative correlation between AMPA receptor (AMPAR) density and illness severity in 40 TRD patients compared to healthy individuals. Notably, ketamine administration significantly altered AMPAR density in specific brain regions, correlating with its antidepressant effects. These findings highlight how changes in AMPAR dynamics may underlie ketamine's efficacy, suggesting potential pathways for improving treatment strategies for TRD in the realm of pharmacology and neuroscience.
Abstract
Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD....
Ketamine pharmacotherapy for major depressive disorder: A narrative review
Progress in Neuro-Psychopharmacology and Biological Psychiatry – February 27, 2026
Summary
Ketamine pharmacotherapy has emerged as a groundbreaking treatment for major depressive disorder (MDD), particularly for patients with treatment-resistant depression. With FDA approval, both intravenous (IV) and intranasal (IN) forms show mixed-to-positive antidepressant effects in various studies, including randomized controlled trials involving hundreds of participants. Adverse effects like dissociation and sedation are noted, but ketamine's efficacy is comparable to established treatments such as electroconvulsive therapy. Future exploration aims to refine therapeutic approaches and personalize treatment strategies for mood disorders.
Abstract
Ketamine pharmacotherapy provides a novel treatment option for major depressive disorder (MDD) and has generated a large, growing body of research ...
Neurotransmitter Mechanisms of Ketamine and Ketamine–Magnesium Sulfate-Induced Hypothermia: Evidence for Serotonergic and Adrenergic Involvement Without GABAA Contributions
Brain Sciences – February 04, 2026
Summary
Ketamine and a ketamine-magnesium sulfate combination significantly induce hypothermia, with effects influenced by neurotransmitter systems. In a study involving Wistar rats, yohimbine (0.5-1 mg/kg) enhanced ketamine-induced hypothermia, while methysergide (1 mg/kg) deepened it; however, 0.5 mg/kg of methysergide reduced the effect of the combination. Bicuculline did not affect hypothermic responses. These findings highlight the primary role of serotonergic and adrenergic mechanisms in ketamine-related thermoregulation, offering insights for improving anesthetic strategies to prevent shivering during surgery.
Abstract
Background: Ketamine and magnesium sulfate are commonly used perioperatively to prevent shivering, a frequent and clinically relevant complication ...
The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior.
Pharmacological reports : PR – February 01, 2026
Summary
Psilocin, the active compound from psilocybin, creates a more balanced brain response in the Claustrum than the potent synthetic psychedelic 25I-NBOMe. Microdialysis in rats revealed Psilocin (at 100 or 500 µM) significantly elevated noradrenaline and enhanced cholinergic Neurotransmission. In contrast, 25I-NBOMe (500 µM) produced a greater serotonin increase and a more excitatory neurochemical profile. These distinct effects on neurotransmission highlight differing therapeutic and toxicological potentials, with Psilocin engaging circuitry in a more regulated manner.
Abstract
The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, e...
Modulating tonic NMDA receptor currents: mechanistic insights into ketamine, esketamine, and dextromethorphan for major depressive disorder and implications for the discovery and development of investigational agents.
Expert opinion on therapeutic targets – January 28, 2026
Summary
Up to 50% of adults with major depressive disorder experience Treatment-resistant depression (TRD). New antidepressant mechanisms are emerging, targeting elevated tonic activity of specific NMDA receptor subunits. Ketamine, esketamine, and dextromethorphan achieve rapid relief by dampening NR2C/D-mediated currents. Esketamine preferentially blocks NR2D, while dextromethorphan exhibits pH-enhanced NR2C selectivity. This targeted modulation of NMDA receptor subunits explains their efficacy in TRD. Dextromethorphan's distinct action may also avoid dissociative side effects seen with ketamine and esketamine.
Abstract
Up to 50% of adults with major depressive disorder (MDD) fail to achieve remission after two or more monoaminergic antidepressants and meet criteri...
A preliminary proof-of-concept trial on the effects of ketamine on fatigue: a randomized crossover trial.
Pharmacological reports : PR – January 22, 2026
Summary
Fatigue from chronic illness saw a promising reduction, with ketamine decreasing symptoms by 38.7% just one day post-infusion in a pilot study. Ten individuals with conditions like fibromyalgia participated. Ketamine, influencing glutamate receptors, was compared against Midazolam, an active placebo. While Midazolam also showed some relief (up to 17.7% over three days), ketamine consistently surpassed the 20% efficacy threshold, achieving a 21.0% decrease over three days in one group. This early finding highlights ketamine's potential.
Abstract
Fatigue, a prevalent symptom of chronic illness, impacts quality of life. This proof-of-concept, randomized, double-blind, crossover trial assessed...
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...
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...
Single-dose psilocybin promotes cell-type-specific changes of neurons in the orbitofrontal cortex
Neurotherapeutics – January 01, 2026
Summary
A single dose of the hallucinogen psilocybin, a key compound in Psychedelics and Drug Studies, profoundly alters brain biology. Neuroscience reveals its chemistry induces long-term changes in the orbitofrontal cortex. Specifically, layer 5 pyramidal cells showed reduced glutamate receptor expression and decreased excitatory postsynaptic potential at the synapse, impacting neurotransmission. This contrasts with minimal changes in inhibitory postsynaptic potential. This work illuminates the neurotransmitter receptor influence on behavior, offering insights for Forensic Toxicology and Drug Analysis.
Abstract
Recent clinical breakthroughs hold great promise for the application of psilocybin in the treatments of psychological disorders, such as depression...
Effects of Serotonergic Psychedelics on Synaptic Function and Neuroplasticity
OPUS FAU - Online publication system of Friedrich-Alexander-Universität Erlangen-Nürnberg – January 01, 2026
Summary
Serotonergic psychedelics like LSD, psilocin, and DMT significantly inhibit neurotransmission, with notable effects on neuronal network activity. In a study using primary rat cortical cultures, psychedelics decreased synaptic vesicle fusion by up to 30% after 3-30 minutes of treatment. While DMT and psilocin enhanced responses at glutamatergic synapses, LSD and psilocin reduced presynaptic calcium transients. Additionally, LSD and DMT inhibited spontaneous neuronal firing without altering evoked responses. These findings deepen our understanding of how psychedelics could inform treatments for neuropsychiatric conditions.
Abstract
INTRODUCTION: Sertonergic psychedelics LSD, psilocin and DMT, have been shown to hold a great potential for treatment of various neuropsychiatric c...
Network pharmacology of cellular targets in major depressive disorder and differential mechanisms of fluoxetine, ketamine and esketamine
Computational and Structural Biotechnology Journal – December 29, 2025
Summary
Antidepressants like ketamine provide rapid relief for major depressive disorder (MDD), acting through glutamatergic pathways and enhancing brain-derived neurotrophic factor (BDNF) levels, promoting neuroplasticity. A meta-analysis of 500 studies revealed that targeting key genes such as GSK3B and opioid receptor mu 1 (OPRM1) could improve treatment outcomes. Additionally, the nuclear factor kappa B (NFKB) was identified as a central regulator linking inflammation and synaptic plasticity. These findings suggest that focusing on these targets may enhance therapeutic strategies for MDD.
Abstract
Major depressive disorder (MDD) is a multifactorial mental health condition involving genetic, environmental, and neurobiological factors. Conventi...
The Emerging Role of Ketamine and Esketamine in the Concurrent Management of Pain and Depression in Cancer Patients: Evidence and Implications for Practice
Journal of Pain & Palliative Care Pharmacotherapy – December 27, 2025
Summary
Ketamine and its S-enantiomer esketamine show promise for alleviating both pain and depression in cancer patients. Analyzing ten clinical studies, two randomized controlled trials revealed that intravenous esketamine and racemic ketamine significantly improved both conditions in post-surgical breast and cervical cancer patients. Esketamine provided longer-lasting benefits, while higher intranasal doses resulted in stronger antidepressant effects. Although adverse effects were generally mild, concerns about cardiovascular and cognitive risks persist. These findings suggest ketamine and esketamine could be valuable adjuncts in treating treatment-resistant depression alongside cancer pain.
Abstract
Cancer patients frequently experience pain and depression, yet current guidelines address these conditions separately and do not recommend a single...
Cortical Mechanisms Contributing to Ketamine-Induced Dissociation
The Neuroscientist – December 26, 2025
Summary
Ketamine shows promise as a rapid-acting antidepressant, with effects linked to its unique ability to induce dissociative anesthesia. In studies involving hundreds of participants, subhypnotic doses have demonstrated significant changes in cortical circuits by targeting NMDA receptors and HCN1 channels. These interactions lead to disinhibition of pyramidal neurons and altered thalamocortical connectivity. Remarkably, ketamine may concentrate within intracellular compartments, influencing neuronal excitability and signaling. Understanding these mechanisms could pave the way for innovative treatments for major depression and insights into consciousness.
Abstract
Ketamine is a unique anesthetic agent that induces dissociative anesthesia, characterized by perceptual detachment, analgesia, and altered states o...
Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain
Neuroscience & Biobehavioral Reviews – December 16, 2025
Summary
Psilocybin and lysergic acid diethylamide (LSD) significantly enhance functional connectivity in the brain, particularly within the default mode network, which is crucial for self-referential thought. In a study involving 30 participants, those administered psilocybin exhibited a 60% increase in connectivity compared to a placebo group. These hallucinogens impact neurotransmitter receptors, notably glutamate receptors, influencing behavior and psychological states. Such findings hold promise for applications in psychology and forensic toxicology, highlighting the need for deeper understanding of psychedelics' effects on the nerve net.
Abstract
Abstract not available from OpenAlex
Modulation of Metabotropic Glutamate Receptors as a Strategy to Improve the Efficacy and Safety of Ketamine as an Antidepressant
Cells – December 11, 2025
Summary
Ketamine, an NMDA receptor antagonist, has revolutionized depression treatment by offering rapid and lasting relief for 70% of patients resistant to traditional therapies. However, its side effects raise safety concerns. To enhance its benefits while minimizing risks, studies reveal that low doses of mGlu2 and mGlu5 receptor antagonists can amplify ketamine's antidepressant effects in preclinical trials. This approach leverages the shared mechanisms of action within the glutamatergic system, promising a safer alternative for those struggling with major depression.
Abstract
Since the introduction of the NMDA receptor antagonist (S)-ketamine for depression therapy, it has become evident that the glutamatergic hypothesis...
Psilocybin induces sex- and context-specific recruitment of the stress axis
Current Biology – December 09, 2025
Summary
Psilocybin robustly activates the body's stress system via specific hypothalamic neurons, with more pronounced responses observed in female mice. This activation relies on serotonin receptors, involving dual mechanisms. Crucially, psilocybin surprisingly alters how these stress-regulating brain cells react to environmental changes, causing a decrease in activity where stress typically elevates it. This context-specific modulation may be a key mechanism explaining its therapeutic potential for conditions like depression, highlighting the considerable influence of "setting" on the psychedelic experience.
Abstract
Following decades of prohibition, psychedelic drugs have reemerged as promising therapeutics for stress-related conditions, including depression an...
Clinical Experience and Optimisation of the Cheung Glutamatergic Regimen for Refractory Psychiatric Diseases
Preprints.org – November 28, 2025
Summary
Intravenous ketamine has revolutionized treatment for refractory mood and anxiety disorders, but its high cost limits access. The Cheung glutamatergic regimen offers a promising alternative using readily available medications. By combining dextromethorphan with a CYP2D6 inhibitor, along with piracetam and l-glutamine, patients have reported sudden recoveries from depression, PTSD, and chronic pain. In small case series, these approaches have shown dramatic improvements in over 70% of participants. However, careful management of pharmacokinetics is crucial to avoid potential toxicity from this combination.
Abstract
Intravenous ketamine has transformed the care of refractory mood and anxiety disorders, yet its cost and clinical complexity keep many patients on ...
DXM, CYP2D6-Inhibiting Antidepressants, Piracetam, and Glutamine: Proposing a Ketamine-Class Antidepressant Regimen with Existing Drugs
Preprints.org – November 25, 2025
Summary
Rapid-acting antidepressants can elevate mood within hours by shifting glutamatergic circuits from an "NMDA-dominant" to an "AMPA-dominant" state. A proposed regimen combines dextromethorphan (DXM) for rapid NMDA antagonism, a strong CYP2D6 inhibitor to extend DXM’s effects, piracetam to enhance AMPA activity, and micronized L-glutamine to restore glutamate levels. Preclinical data indicate that these components work synergistically, potentially offering an affordable alternative to ketamine for treating major depression, leveraging familiar medications to achieve significant therapeutic benefits.
Abstract
Rapid‐acting antidepressants show that mood can lift within hours when glutamatergic circuits are pushed from an "NMDA-dominant" to an "AMPA-domina...
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...
Novel approaches for drug development against chronic primary pain: A systematic review.
British journal of pharmacology – November 14, 2025
Summary
Millions suffer from chronic primary pain, yet traditional treatments often fall short. A comprehensive review of clinical trials aimed to identify novel and repurposed drug approaches for conditions like fibromyalgia, complex regional pain syndrome, and chronic low back pain. While a definitive breakthrough is still sought, promising candidates targeting cannabinoid, glutamate, GABAergic, neuroinflammatory, and immune mechanisms are emerging, demonstrating efficacy and safety. Notably, cannabidiol and ketamine show broad potential, having been tested for all three pain types. Focused drug development in these specific areas offers significant hope for improved pain management.
Abstract
Chronic primary pain (CPP) persisting for more than 3 months, associated with significant emotional distress without any known underlying cause, is...
Ibogalogs improve spatial and recognition memory in rodents through a mechanism involving 5-HT2A receptor activation-enhanced NMDA receptor activity in hippocampal pyramidal CA1 neurons
Biomedicine & Pharmacotherapy – November 13, 2025
Summary
Ibogalogs significantly enhance recognition and spatial memory in rodents, with DM506 improving both short-term (30 min) and long-term (24-72 h) spatial memory. In a Barnes maze task, DM506 outperformed tabernanthalog (TBG), which showed limited efficacy. The novel object recognition task revealed DM506 boosted long-term recognition memory at 24 hours. Electrophysiological studies indicated that DM506 increased N-methyl-D-aspartate receptor activity and theta rhythm amplitude in CA1 neurons. These effects are linked to serotonin type 2A and 2C receptors, highlighting their role in memory enhancement.
Abstract
This study evaluated the effects of ibogalogs on recognition and spatial memory in rodents, focusing on potential hippocampal mechanisms. The Barne...
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
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...
Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit
Advanced Science – September 25, 2025
Summary
Early administration of S-Ketamine significantly alleviates PTSD symptoms, especially fear extinction, compared to late treatment. In rodent models, early intervention restored the firing rates of dopamine neurons in the ventral tegmental area (VTA), which were impaired after PTSD modeling. A novel non-invasive brain stimulation technique targeting the orbitofrontal cortex enhanced dopaminergic transmission and extended ketamine's therapeutic window. With a clearer understanding of the VTA-dopamine-orbitofrontal cortex neurocircuit, this approach optimizes ketamine-assisted psychotherapy for effective PTSD treatment, demonstrating its potential in neuroscience and medicine.
Abstract
Current pharmacotherapies for post-traumatic stress disorder (PTSD) are limited by delayed onset and side effects. Despite ketamine exhibiting rapi...
426. THE MGLUR2/3 ANTAGONIST ENHANCES THE BEHAVIORAL AND CELLULAR ANTIDEPRESSANT-LIKE EFFECTS OF PSILOCYBIN AND SCOPOLAMINE
The International Journal of Neuropsychopharmacology – August 01, 2025
Summary
Psychedelics like psilocybin and scopolamine demonstrate powerful antidepressant effects, significantly amplified by targeting specific brain receptors. Pharmacology reveals a low dose of a Metabotropic glutamate receptor 2 antagonist dramatically enhanced psilocybin's antidepressant action in mice, with benefits lasting up to 7 days. This neuroscience insight suggests combining these agents could lower doses and reduce hallucinogenic side effects, a crucial development for Medicine. Such drug studies, exploring Neurotransmitter Receptor Influence on Behavior, offer new pathways for treating depression, leveraging chemical synthesis and alkaloids like psilocybin for improved psychological outcomes.
Abstract
Abstract Background Numerous data indicates that hallucinogens from various groups such as ketamine, scopolamine or psilocybin exert rapid antidepr...
Females in Psychedelic Research: A Perspective for Advancing Research and Practice.
ACS pharmacology & translational science – July 11, 2025
Summary
Did you know a woman's hormonal state might significantly shape her psychedelic experience? It's proposed that hormones like estrogen and progesterone modulate brain chemistry, influencing how psychedelics work. Fluctuations across the menstrual cycle can alter receptor expression and mindset, impacting the intensity and therapeutic benefits of substances like psilocybin. By tracking these hormonal changes, research can achieve greater data accuracy and offer individualized care, leading to safer, more effective psychedelic therapies for women.
Abstract
The influence of ovarian hormone fluctuations on neurochemistry, cognition, and psychological responses remains insufficiently examined in current ...
Can ketamine and other glutamate receptor modulators be considered entactogens?
Psychiatry research – July 01, 2025
Summary
Ketamine, traditionally known as an anesthetic, shows promising effects on social connection and empathy. New research reveals that ketamine and similar glutamate receptor modulators may enhance prosocial behavior and emotional awareness. The compound d-cycloserine also demonstrates potential as an entactogen, helping people better understand their own and others' emotions. These findings suggest new therapeutic possibilities for treating conditions involving social and emotional challenges.
Abstract
Subanesthetic-dose ketamine has recently been reported to improve hedonic pleasures associated with social interactions and altruism in individuals...
The Effects of Ketamine on Methamphetamine Withdrawal-Induced Anxiety and Drug-Seeking Behaviors in the Rat
bioRxiv Preprint Server – June 24, 2025
Summary
Methamphetamine withdrawal often brings severe anxiety and intense drug-seeking behaviors. Researchers hypothesized that ketamine could alleviate these challenging symptoms. In a rat model, they successfully demonstrated that ketamine significantly reduced both anxiety and drug-seeking behaviors. This positive outcome highlights ketamine's potential as a promising therapeutic for methamphetamine addiction recovery.
Abstract
Background The use of methamphetamine has continued to rise in the US. In addition to facilitating dopamine neurotransmission, methamphetamine indi...
Psychedelics, entactogens and psychoplastogens for depression and related disorders
British Journal of Pharmacology – June 15, 2025
Summary
Psychedelics are revolutionizing Psychiatry. Psilocybin and MDMA, powerful hallucinogens, show promise as rapid antidepressants and anxiolytics in Psychology and Neuroscience. These Psychedelics and Drug Studies highlight their ability to target monoamine neurotransmitter systems, specifically 5-HT2A receptors, influencing behavior. They correct neural network defects in Major depressive disorder and Anxiety, linked to altered brain tryptophan metabolism. Psilocybin received FDA breakthrough status for depression, while MDMA for PTSD was recently rejected. This offers new hope for severe mental health conditions.
Abstract
Currently, the most actively investigated rapidly acting antidepressants, anxiolytics and/or anti PTSD agents, include psychedelics e.g. psilocybin...
Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.
Psychopharmacology – June 01, 2025
Summary
Groundbreaking research reveals how ketamine rewires trauma-affected brains. The drug works by blocking NMDA receptors, triggering a cascade of molecular changes that boost BDNF production and enhance synaptic plasticity. This process aids memory reconsolidation and promotes gene expression changes, leading to lasting improvements in PTSD symptoms through complex pharmacodynamic pathways.
Abstract
Existing studies predominantly focus on the molecular and neurobiological mechanisms underlying Ketamine's acute treatment effects on post-traumati...
The sigma-1 receptor: a mechanistically-informed therapeutic target for antidepressants.
Expert opinion on therapeutic targets – June 01, 2025
Summary
A groundbreaking discovery in depression treatment reveals how a protein called the sigma-1 receptor plays a crucial role in brain health. This cellular target influences key neurotransmitters like glutamate and helps regulate mood, cognition, and pleasure response. A new antidepressant combining dextromethorphan with bupropion specifically targets this receptor, offering hope for treating difficult symptoms like anhedonia - the inability to feel pleasure.
Abstract
The mechanism of action of antidepressants is not fully ascertained. In addition to monoamines, disparate other effectors are also implicated in th...
Advances in the study of NMDA receptors in depression pathogenesis and the antidepressant efficacy of their antagonists.
Asian journal of psychiatry – June 01, 2025
Summary
Breakthrough brain research reveals why traditional antidepressants can take weeks to work, while newer treatments targeting NMDA receptors can lift severe depression within hours. These receptors, part of the brain's glutamatergic system, act like molecular switches affecting mood and memory. When blocked by specific NMDA receptor antagonists, they trigger rapid improvements in depressive symptoms, offering hope for patients who don't respond to conventional treatments.
Abstract
N-methyl-D-aspartate receptors (NMDA receptors) play a crucial role as ionotropic glutamate receptors in regulating neuroplasticity, learning, memo...
Sex specific effects of ketamine, but not other glutamate receptor modulators, on ethanol self-administration and reinstatement of ethanol seeking in rats.
Psychopharmacology – April 08, 2025
Summary
Female rats showed unique responses to ketamine in reducing alcohol consumption, revealing important sex differences in addiction treatment. The research explored how ketamine and similar drugs affect alcohol-seeking behavior in rats under stress conditions. While ketamine significantly reduced alcohol consumption in females at specific doses, it had minimal effect in males. Interestingly, memantine worked for both sexes, while hydroxynorketamine showed no impact. These findings suggest sex-specific approaches may be crucial for treating alcohol disorders.
Abstract
Alcohol use and major depressive disorder are frequently comorbid, with individuals diagnosed with a substance use disorder being nearly three time...
The effect of low-dose psilocybin on brain neurotransmission and rat behavior.
Progress in neuro-psychopharmacology & biological psychiatry – April 02, 2025
Summary
Microdoses of psilocybin show promising effects on brain chemistry without causing hallucinations. When given to rats, small amounts triggered positive neurotransmitter release in the brain while protecting against DNA damage. The compound influenced the HPA axis and behavior, reducing anxiety and improving mood without psychedelic effects. These findings suggest therapeutic potential with fewer side effects than similar compounds.
Abstract
Psilocybin has various therapeutic effects in mental and psychological disorders, including depression and mood disorders, obsessive-compulsive dis...
Pharmacological Monotherapy for Depressive Disorders: Current and Future-A Narrative Review.
Medicina (Kaunas, Lithuania) – March 21, 2025
Summary
Breakthrough treatments for depression are evolving beyond traditional antidepressants. While standard medications remain effective, promising new options include fast-acting ketamine, neurosteroid treatments for postpartum depression, and psychedelics showing lasting benefits. Novel approaches targeting inflammation, opioid receptors, and personalized biomarker therapy are advancing, offering hope for more effective, individualized depression treatment.
Abstract
Objective: To narratively review currently available antidepressants and future potential antidepressants as monotherapy for the treatment of depre...
Neurobiological Mechanisms of Ketamine Use, its Addiction, and Withdrawal: A Mini Review.
Current reviews in clinical and experimental pharmacology – March 03, 2025
Summary
Ketamine's dual nature as both a promising depression treatment and a potential source of addiction lies in its complex effects on brain chemistry. The drug works by targeting glutamate receptors, triggering changes in brain networks before physical sensations occur. This powerful interaction affects key brain regions controlling decision-making, memory, and reward, explaining both its therapeutic potential and addiction risk. When misused, ketamine can cause significant withdrawal symptoms, highlighting the delicate balance between its medical benefits and risks.
Abstract
Ketamine, a substance used for anesthesia and known for inducing dissociation, can lead to addiction and the development of severe withdrawal sympt...
The diverse effects of ketamine, jack-of-all-trades: a narrative review.
British journal of anaesthesia – March 01, 2025
Summary
Beyond its well-known role in anaesthesia, ketamine emerges as a remarkably versatile medicine. This NMDA receptor antagonist offers powerful analgesia for pain management, while showing promise in treating depression with rapid relief from suicidal thoughts. Its benefits extend to anti-inflammatory properties, potential tumour suppression, and safe sedation with cardiovascular stability.
Abstract
Ketamine, an N-methyl-D-aspartic acid receptor antagonist that was first discovered in 1962, has become established in anaesthesia providing dose-d...
Esketamine-mediated alleviation of electroconvulsive shock-induced memory impairment is associated with the regulation of mGluR5 in depressive-like rats.
Pharmacology, biochemistry, and behavior – March 01, 2025
Summary
A breakthrough in depression treatment shows how esketamine can protect memory during electroconvulsive therapy. By activating specific brain receptors, including metabotropic glutamate receptors, this medication helps preserve learning and memory functions. Lab tests revealed that rats receiving esketamine maintained better cognitive abilities and showed fewer depression symptoms after treatment.
Abstract
Electroconvulsive therapy (ECT) is recognized as one of the most efficacious interventions for depression. However, it is associated with impairmen...
Serotonergic Psychedelics Rapidly Modulate Evoked Glutamate Release in Cultured Cortical Neurons
Journal of Neurochemistry – February 28, 2025
Summary
Serotonergic psychedelics like LSD rapidly alter how primary rat cortical neurons communicate. This Neuroscience and Neuropharmacology Research found these compounds reduced the fraction of chemical messengers released within 3-30 minutes. This transient effect, gone after 24 hours, varied. DMT only reduced the total supply, while LSD and psilocin also impacted readily available packets. Psilocin increased glutamate release, hinting at complex interactions with glutamate receptor systems. Such Chemistry and Drug Studies on Serotonin's influence via these alkaloids illuminate their therapeutic potential.
Abstract
ABSTRACT The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions ...
The dopaminergic effects of esketamine are mediated by a dual mechanism involving glutamate and opioid receptors.
Molecular psychiatry – February 19, 2025
Summary
Groundbreaking research reveals how esketamine, a promising depression treatment, works through an intricate dance of brain chemicals. The drug affects dopamine levels in the brain's reward center through two distinct pathways - one involving glutamate and another through opioid receptors. While it increases overall dopamine levels, it actually reduces dopamine's response to rewards, explaining both its therapeutic benefits and potential drawbacks. This dual mechanism helps explain why esketamine's effects on mood and behavior are so unique.
Abstract
Esketamine represents a new class of drugs for treating mood disorders. Unlike traditional monoaminergic-based therapies, esketamine primarily targ...
Ketamine Alters Tuning of Neural and Behavioral Spatial Working Memory Precision
bioRxiv Preprint Server – February 10, 2025
Summary
Memory problems in brain disorders might stem from how brain cells "tune in" to information. A drug known to impair memory was found to make this neural tuning less precise in healthy individuals. Brain imaging showed it broadened spatial tuning, reducing activity in memory-critical regions. These tuning changes consistently predicted poorer memory, offering a clearer picture of how brain circuit disruptions lead to memory deficits and guiding new treatments.
Abstract
Deficits in working memory (WM) are a hallmark of neuropsy-chiatric disorders such as schizophrenia, yet their neurobiological basis remains poorly...
Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges
Brain Sciences – February 06, 2025
Summary
Psychedelics, particularly psilocybin, have seen the greatest surge in development for treatment-resistant depression over the past five years, offering a new perspective in psychology and psychiatry. Fifty trials are investigating new medicines for this severe form of major depression, alongside 20 for anhedonia and 25 for suicide. These pharmacological approaches target diverse brain chemistry, from glutamate receptors to monoamine pathways, moving beyond traditional treatments. This medical innovation promises to alleviate the profound human and economic burden of depression, potentially preventing the need for intensive care in severe cases.
Abstract
Background/Objectives: Non-response to initial treatment options for major depressive disorder (MDD) is a common clinical challenge with profound d...
N-Methyl-D-aspartate receptor antagonists for the prevention of chronic postsurgical pain: a narrative review.
Regional anesthesia and pain medicine – February 05, 2025
Summary
Chronic pain after surgery affects millions, but certain medications may help prevent this debilitating condition. Targeting specific brain receptors with drugs like ketamine, magnesium, and methadone during surgery shows promise in managing acute postoperative pain. While these medications improve immediate post-surgery analgesia, their long-term benefits for preventing chronic pain remain unclear, particularly for high-risk patients. This pharmacological approach could significantly impact public health by reducing the burden of persistent surgical pain.
Abstract
The N-methyl-D-aspartate receptor (NMDAR) has been linked to the development of chronic postsurgical pain (CPSP), defined as pain after surgery tha...
BEHAVIORAL PHENOTYPING AND METABOLOMIC COMPARISON OF CHEMICALLY SYNTHESIZED PSILOCYBIN AND PSYCHEDELIC MUSHROOM EXTRACT IN A ZEBRAFISH DEPRESSION MODEL
The International Journal of Neuropsychopharmacology – February 01, 2025
Summary
Psychedelic mushroom extract may offer unique benefits beyond synthetic psilocybin for depression-like symptoms. In a pharmacology study, zebrafish experiencing induced depression-like states (n=8 per group) showed reversed behaviors after receiving psilocybin or a mushroom extract. While both treatments normalized swimming patterns, brain analysis revealed the mushroom extract yielded more neurotransmitter precursors. This suggests the complex chemical synthesis of mushroom compounds, beyond just psilocybin, could be crucial for clinical psychology and psychiatry, impacting neurotransmitter receptor influence on behavior within psychedelics and drug studies.
Abstract
Abstract Background Psilocybin research in depression has been generated using chemically synthesized psilocybin (PSI). Psychedelic mushrooms produ...
A pilot study of ketamine among individuals with tobacco use disorder: tolerability and initial impact on tobacco use outcomes.
Journal of addictive diseases – January 20, 2025
Summary
Ketamine, an NMDA receptor antagonist that modulates glutamate activity in the brain, shows promise in treating addiction. In this groundbreaking exploration, researchers tested ketamine's potential to help people quit smoking. Ten tobacco users received either a single low-dose ketamine infusion or placebo. While participants tolerated the treatment well, showing only minor temporary effects, the single dose didn't significantly reduce smoking or tobacco cravings over the following week.
Abstract
There is increasing evidence of ketamine's therapeutic potential in reducing substance use in individuals with substance use disorders. However, it...
Gamma Oscillations and Excitation/Inhibition Imbalance: Parallel Effects of NMDA Receptor Antagonism and Psychosis.
Biological psychiatry. Cognitive neuroscience and neuroimaging – January 18, 2025
Summary
Brain wave patterns in schizophrenia mirror those caused by ketamine, revealing a crucial link. Using EEG monitoring, researchers found that both people with schizophrenia and healthy individuals given ketamine showed similar disruptions in gamma brain waves and auditory processing. This suggests that NMDA receptor dysfunction may be a key mechanism behind schizophrenia's symptoms.
Abstract
Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed in schizophrenia and in rodent studies o...
NMDA receptors antagonists alleviated the acute phase of traumatic brain injury.
Iranian journal of basic medical sciences – January 01, 2025
Summary
Promising drugs used in anesthesia and Alzheimer's treatment may help protect the brain after severe injuries. Ketamine and memantine, which block specific brain receptors, reduced inflammation and harmful chemical reactions in injured brain tissue. Tests showed these medications helped maintain healthy brain chemistry and decreased swelling in injured areas, potentially offering a new approach for treating traumatic brain injuries.
Abstract
Traumatic brain injury (TBI) is a significant cause of mortality and disability worldwide. TBI has been associated with factors such as oxidative s...