Major depressive disorder (MDD) is a highly prevalent psychiatric illness for which rapid-acting antidepressants such as ketamine provide only transient benefit. Because κ-opioid receptor (KOR) signaling contributes to stress-related dysphoria and impaired neuroplasticity, we examined whether KOR antagonism could prolong ketamine’s antidepressant-like effects in a mouse model of adolescent...
To investigate the regulatory role of glutamatergic neurons in the medial prefrontal cortex (mPFC) in the antidepressant effects of esketamine. A total of 150 male C57BL/6J mice were randomly divided into 15 groups (n=10). The mice subjected to the chronic restraint stress (CRS), and those exhibiting depressive-like behaviors following CRS received either esketamine or saline treatment, and...
Psilocybin, N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are psychedelic compounds with therapeutic potential for depression, anxiety, and post-traumatic stress. However, their relevance to endurance athletes, who face particular psychological and physical stressors, remains underexplored. This study combines a conceptual overview...
Adolescent major depressive disorder (MDD) is a leading cause of disability worldwide and a major, modifiable risk factor for suicide, which remains the second leading cause of death in this age group.1 For 30% to 50% of patients who fail to achieve remission despite multiple treatment steps, the clinical and psychosocial consequences are substantial.2 Although selective serotonin-reuptake...
BACKGROUND: Intranasal esketamine has recently emerged as an innovative treatment option for treatment-resistant depression (TRD). This retrospective, uncontrolled study aimed to evaluate the real-world effectiveness of esketamine in an naturalistic inpatient setting and explore demographic and clinical factors associated with treatment response. METHODS: We conducted a chart review of 101...
RATIONALE: Major Depressive Disorder (MDD) is a global public health burden, with traditional monoaminergic antidepressants facing critical limitations including slow onset, adverse side effects, and high rates of treatment resistance (TRD). Ketamine, a rapid-acting agent with sustained antidepressant effects, has revolutionized depression treatment paradigms but challenges conventional...
Ketamine produces rapid antidepressant and antidepressant-like effects in both humans and animal models. However, its therapeutic benefits are tempered by psychoactive side effects, such as hyperlocomotion associated with enhanced dopaminergic activity in the ventral tegmental area (VTA). We tested the therapeutic effect of cannabidiol (CBD) on locomotor activity after systemic (30 mg/kg) or...
Treatment-resistant depression (TRD) remains a major clinical challenge, with inflammation increasingly implicated in its pathophysiology. C-reactive protein (CRP), an accessible biomarker, has emerged as a potential predictor of antidepressant response. While intravenous and intranasal ketamine have shown anti-inflammatory effects, evidence linking inflammation and clinical outcomes remains...
Treatment-resistant depression (TRD) presents a complex clinical challenge, particularly when comorbid with substance use disorders (SUDs) or other compulsive behaviors. With up to a third of major depressive disorder (MDD) patients failing to respond to standard antidepressant therapies, there is growing interest in interventions such as esketamine, a glutamatergic N-methyl-D-aspartate (NMDA)...
Major depressive disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disease. Recent data show an increasing prevalence of treatment-resistant depression (TRD). Patients with autism spectrum disorder (ASD) often exhibit MDD as a comorbidity and it is often resistant to conventional treatments. ASD determines emotional dysregulation and...
Aims The recent regulatory approval of esketamine in adults heralded the renaissance of research into psychedelic compounds. However, the relevance of this resurgence for children and adolescents remains unclear. This review examines the rationale for investigating psychedelics in pediatric psychopharmacology. Methods We reviewed recent literature, regulatory documents, and clinical trial...
Traumatic brain injury (TBI) is a major global health issue leading to high mortality and disability. Activated astrocytes are one of the pivotal driving factors in the neuroinflammatory cascade following TBI. This study aims to investigate the role of esketamine on TBI and the underlying mechanism. Mice received a mouse weight-drop cortical impact or sham surgery and TBI mice were treated with...
Cocaine and methamphetamine use disorders pose public health concerns due to the high propensity for relapse driven by persistent drug-associated memories. Output from the medial prefrontal cortex (mPFC) regulates relapse and is controlled by parvalbumin (PV) interneurons, which are surrounded by perineuronal nets (PNNs) that support precise PV neuron firing. We previously showed that removal...
Bloy et al. [1] provide an important and methodologically rigorous secondary analysis of the Ketamine for the reduction of Alcoholic Relapse (KARE) trial, examining whether acute psychoactive effects mediate the therapeutic impact of ketamine in alcohol use disorder (AUD). Their finding that dissociative and perceptual effects did not mediate abstinence outcomes is clinically relevant, and...
Background: Treatment-Resistant Depression (TRD) often persists despite adequate pharmacotherapy. Intranasal Esketamine and accelerated repetitive Transcranial Magnetic Stimulation (aTMS) are rapid-acting options, but head-to-head comparisons remain limited. Methods: We conducted a retrospective study on TRD patients receiving either aTMS (n = 18) or Intranasal Esketamine (n = 22). Depression...
Recent retrospective analyses have shown that individuals with comorbid Substance Use Disorders (SUDs) are overrepresented among responders to ketamine for Treatment Resistant Depression (TRD). Ketamine is an effective treatment for depression and also a potential substance of misuse. The authors contrast a mechanistic pathway with a possible expectancy effect to account for these findings, and...
Esketamine (ESK), the dextrorotatory enantiomer of ketamine, is an antagonist of the N-methyl-D-aspartic acid (NMDA) receptor. ESK is considered an effective anesthetic because of its ability to mitigate postoperative pain and opioid use. Recently, it has attracted significant research attention for its fast-acting antidepressant effects. Given the advantages of ESK in both perioperative and...
Abstract Ketamine’s rapid neuropsychiatric actions emerge from interactions that span receptors, cells, and circuits, but their net effects on human neuronal population dynamics remain incompletely defined. Here we combine human dorsal forebrain organoids with high-density microelectrode arrays (MEAs) to quantify ketamine’s effects from spikes to networks. In 6-month-old organoids, acute...
Background: Anhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antidepressants.Ketamine has rapid antidepressant effects, yet its neurofunctional actions within reward circuits remain unclear.We synthesized human neuroimaging evidence on ketamine-related modulation of reward circuitry and implications for...
Background Though esketamine was approved by the Food and Drug Administration (FDA) for treatment-resistant depression in 2019, there is no published research on implementation challenges. Therefore, the aim of this study was to investigate online commentary about these challenges among mental healthcare providers. Methods Using the terms “esketamine” and “Spravato”, the author searched social...