Background and aimFunctional neurological disorder (FND) is a common and disabling condition for which effective treatments remain limited. Clinical outcomes are often variable, particularly in chronic and comorbid presentations. Ketamine and esketamine are increasingly used across a range of neuropsychiatric conditions. This review aimed to synthesise the existing evidence regarding their use...
Intranasal ketamine represents a rapid and minimally invasive antidepressant strategy, yet the molecular mechanisms underlying its antidepressant-like effects after intranasal administration remain incompletely understood. Male Sprague-Dawley rats were subjected to a 28-day chronic unpredictable mild stress (CUMS) paradigm and then received intranasal racemic ketamine at 8.58 mg/kg twice weekly...
Esketamine nasal spray (NS) is an established treatment for patients with treatment resistant depression (TRD). To further optimise real-world outcomes, consensus is needed regarding strategies to enhance patient outcomes and decision-making factors for pivotal timepoints in esketamine NS treatment. This modified Delphi panel (3 rounds) established expert consensus (≥80% agreement) from 30...
Introduction Substance use disorder (SUD) is a major global health issue, contributing significantly to the disease burden. Despite this, effective treatments for SUD remain limited. Ketamine has shown potential as a treatment, yet no meta-analysis has assessed its efficacy for SUD. This study aimed to evaluate the efficacy and safety of ketamine in treating SUD. Methods Multiple databases were...
Zenodo (CERN European Organization for Nuclear Research)July 17, 2026Bartosz Niciński, Magdalena Kloc, Ewa Wiench, Natasza Millan, Aleksandra Blicharz, Wojciech Kozdraś, Lidia Kozaczko, Gabriela Szewczyk, Elżbieta Bukowczan, Alicja Zając, Damian Broda, Alicja Benecka
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Major depressive disorder is a highly burdensome psychiatric condition worldwide, and many patients do not achieve full remission after standard monoaminergic antidepressant treatment. This has contributed to growing interest in rapid-acting antidepressant interventionstargeting neurobiological pathways beyond traditional serotonin, norepinephrine, and dopamine mechanisms. This review...
Background. Post-Traumatic Stress Disorder (PTSD) is an important public health challenge typically treated with trauma-focused psychotherapy and Selective Serotonin Reuptake Inhibitors (SSRIs). However, high rates of residual symptoms associated with these standard treatments have led to a renewed interest in psychedelic-assisted therapies. Aim. This review attempts to examine emerging...
Ketamine and its enantiomer esketamine are efficacious in 30-35% of the patients with treatment-resistant depression (TRD). Increased serum brain-derived neurotrophic factor (BDNF) following treatment has been proposed as a potential biomarker of antidepressant response. This is based on studies evaluating single intravenous ketamine treatment. BDNF expression at different treatment schedules...
Major depressive disorder (MDD) is a leading cause of disability worldwide, with a significant portion of patients experiencing treatment-resistant depression (TRD). Ketamine, a rapid-acting antidepressant, has shown promise in alleviating symptoms of TRD and suicidality, but variability in treatment response remains a challenge. Identifying neuroimaging biomarkers that predict responsiveness...
This paper proposes treating N-methyl-D-aspartate (NMDA) receptor modulation as a single bidirectional pharmacological axis, with ketamine (an NMDA antagonist) and glycine-site enhancers such as sarcosine and D-serine (NMDA agonists/enhancers) sitting at opposite poles. Both directions have documented human trial evidence, but in separate literatures — ketamine in anesthesia and depression...
In humans, researchers can readily query the subjective states elicited by drugs of abuse, but no such introspective readout is currently available in rodents. Rats can convey information relevant to their internal states via ultrasonic vocalizations (USVs). We sought to measure USVs and locomotor behavior as parallel behavioral indices of the effects of drugs and ventral tegmental area...
The introduction of ketamine and its S-enantiomer, esketamine, has been one of the most consequential advances in treatment-resistant depression (TRD) in recent decades, demonstrating that rapid and clinically meaningful antidepressant effects can occur within hours, even in patients who have not responded to conventional treatments.However, this advance has not resolved the clinical problem of...
In acute trials of intravenous and intranasal ketamine/esketamine, the rapid anti-suicidal effect appears to be at least partly independent of the overall antidepressant response. That question has, to our knowledge, never been examined in a real-world esketamine cohort followed for six months, nor in a sample enriched for comorbid borderline personality disorder (BPD), a population excluded...
Altered-state phenomenology around ketamine may relate to longer-term changes in imaginal processes, but observations across routine care are scarce. We report an educational case focusing on pre-defined dream motifs over time, without making treatment efficacy claims. A 48-year-old Japanese man with severe chronic primary low back pain reported dreams during insight-oriented psychotherapy from...
The occupancy-driven pharmacology model in psychopharmacology has guided drug discovery and development for decades, whereby the goal is stable receptor occupancy over an extended period with a direct relationship of drug exposure to pharmacodynamic and therapeutic response. Event-driven pharmacology (EDP) is a concept where the acute pharmacodynamic actions of a plastogen, a transient binding...
Background and Purpose: Ketamine has emerged as a promising treatment candidate for alcohol use disorder (AUD), yet whether its S- and R-enantiomers differentially regulate ongoing binge-like alcohol self-administration remains unknown. We compared the acute and repeated effects of S- and R-ketamine in a chronic binge-like, front-loaded operant alcohol self-administration paradigm. Experimental...
Psychoplastogen compounds such as ketamine and MDMA have shown therapeutic promise for mood and trauma-related disorders, yet the molecular mechanisms underlying their effects remain poorly understood. Here, we applied a Brain-Epigenome-Wide Association Study (BEWAS) targeting brain-relevant genes to examine DNA methylation changes following treatment. Pre- and post-treatment blood (ketamine, N...
Background: Jobelyn® (JB) is a polyherbal formulation with proven benefits on psychosis, a psychiatric disorder, validated in dopamine-agonist models. However, its effect in ketamine, a glutamate antagonist, is linked to schizophrenia's pathology due to N-methyl-D-aspartate (NMDA) receptor hypofunction, which remains largely unknown. Hence, this study investigates the antipsychotic effectsof JB...
Classic psychedelics such as lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), and mescaline induce lasting changes in neuroplasticity and behavior that extend far beyond their acute pharmacological effects. Emerging evidence highlights that these enduring therapeutic benefits in neuropsychiatric conditions may be significantly mediated through complex epigenetic...
Research SquareJuly 9, 2026Samuel Westenhöfer, Yamina Ehrt, Barbora Provaznikova et al.
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Abstract Background : Treatment-resistant depression (TRD) is associated with substantial clinical and socioeconomic burden. Intranasal esketamine has shown efficacy for TRD in clinical trials and real-world studies. However, evidence on optimal maintenance scheduling is limited. We therefore investigated whether two maintenance schedules differing in their inter-dose intervals were associated...
Intravenous ketamine is used for treatment-resistant depression, with structured guidelines supporting its use, but requires careful patient monitoring due to potential side effects and variable efficacy.