Ketamine and its structural analog, 2-Fluorodeschloroketamine, both potent stimulants, can induce euphoria but also cause neurotoxicity, cognitive decline, and neurodevelopmental deficits in the fetus. However, the molecular mechanisms responsible for these neurodevelopmental abnormalities are not yet fully elucidated, particularly concerning effects that are specific to certain cell types....
Background: Ensuring participants understand informed consent forms (ICFs) is a core ethical requirement of clinical research, particularly in psychiatry, where cognitive and affective symptoms can compromise decisional capacity. As ketamine-based interventions are increasingly studied for mental health conditions, the readability of consent materials in these trials warrants systematic...
Ketamine is an indispensable therapeutic in emergency medicine, yet its pharmacologic profile carries a unique constellation of adverse effects that emergency medicine clinicians must recognize and manage. This focused clinical review examines four categories of these ketamine-specific adverse effects encountered in the emergency department (ED): acute psycho-perceptual adverse effects (PPAEs)...
Ketamine is an antagonist of the N-Methyl-D-aspartate (NMDA) receptor with the effect of inducing aberrant excitatory-inhibitory neurotransmission and oxidative neurotoxicity, which mimic the cognitive impairments found in schizophrenia. This study explored the potential of mangiferin, a strong antioxidant xanthone polyphenol, to normalize neurotransmitter levels and mitigate oxidative and...
Introduction: Treatment-resistant depression (TRD) is a major public health and societal challenge, associated with persistent symptoms, functional impairment, and increased healthcare and economic burden. Intranasal esketamine has emerged as a rapid-acting adjunctive therapy with a distinct glutamatergic mechanism of action. This systematic review summarizes current evidence on its...
Oral S-ketamine (S-KETPO) is being explored as an alternative to intravenous maintenance treatment (S-KETIV) in treatment-resistant depression (TRD). However, the first-pass effect with S-KETPO significantly alters S-ketamine's bioavailability and the systemic exposure of its active metabolites, raising potential safety and efficacy concerns. This study characterized the pharmacodynamic and...
Depression and its severe outcomes, suicidal ideation and behavior, are exacerbated by stress. A broad literature links dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) stress response system to depression, suicidal ideation and behavior. Our midazolam-controlled clinical trial of subanesthetic, intravenous ketamine infusion for suicidal depressed patients found rapid reduction...
Ketamine, a dissociative anesthetic, induces behavioral and molecular alterations associated with psychosis-like phenotypes. However, the epigenetic mechanisms bridging its cellular effects with behavioral outcomes are poorly defined. Here, we report that ketamine induces histone H3 Ser10 phosphorylation in both hippocampal neurons (HT22 cells) and the mouse hippocampus, an effect primarily...
Background: Treatment-resistant depression (TRD) is associated with substantial functional impairment, suicide risk, and health-care costs. Ketamine and its S-enantiomer, esketamine, have emerged as rapid-acting glutamatergic treatment options for TRD. Aim: This review aims to synthesize current evidence on the different ketamine administration routes for TRD, with a focus on acute and...
Ketamine has emerged as a promising rapid-acting treatment for mood disorders and suicidality. Notwithstanding its replicated antidepressant efficacy, ketamine-associated risk for abuse, dependence, and misuse remain. We conducted a systematic review of clinical and preclinical studies from database inception to August 2025, including randomized and observational trials, open-label extensions,...