medRxiv Preprint Server
March 31, 2026
Maia Mallevays, Louise Fuet, Michel Danon et al.
1 citation
preprint
Esketamine is a fast-acting antidepressant drug which induces acute psychoactive effects. The most frequent is a dissociative state which seems unrelated to therapeutic efficacy. Other esketamine-induced effects, including psychedelic-like mystical experiences, have been poorly studied in terms of phenomenology and frequency, and may carry specific therapeutic relevance. In this study, we...
J Int Med Res
March 29, 2026
Hui Li, Jingjing Deng, Tao Liu et al.
Ketamine, a dissociative anesthetic, has been extensively used in clinical anesthesia and sedation. However, its use in general anesthesia is gradually declining because of numerous adverse effects. In 2019, esketamine was introduced to the Chinese market. This narrative review aimed to summarize the current status of clinical applications and research progress of esketamine and to explore its...
Behavioural Brain Research
March 28, 2026
Lucas Villar Pedrosa Da Silva Pantoja, Luiza Fernanda Ramos Soares, Brenda Costa Da Conceição et al.
Adolescence is a period of profound behavioral changes associated with high brain vulnerability to negative stimuli including psychotropic drugs misuse which may contribute to the development of psychiatric disorders. Ketamine, an NMDA receptor antagonist, is an anesthetic agent used in a recreational manner in night clubs and raves, especially by intranasal route. The psychedelic effects of...
Psychopathology
March 27, 2026
Xiaoran Ding, Yaping Wu, Juan Yang et al.
1 citation
Ketamine has emerged as a promising rapid-acting antidepressant with distinct advantages for the treatment of treatment-resistant depression (TRD). Its therapeutic effects are mediated through multi-target modulation of the glutamatergic system. Unlike conventional antidepressants, ketamine exerts a markedly faster onset of action; however, its long-term safety profile and potential risk of...
Medicine Advances
March 27, 2026
Thomas Edward Cutting, Richard Evans Hartman
ABSTRACT Numerous studies have demonstrated the efficacy of (R, S)‐ketamine as a treatment for post‐traumatic stress disorder (PTSD), treatment‐resistant depression, and comorbid occurrences of these conditions. The (R) and (S) stereoisomers of ketamine have also demonstrated efficacy in attenuating stress and depressive symptoms, with (R)‐ketamine demonstrating reduced abuse potential and side...
Behavioral Sciences
March 24, 2026
J. Richard Kendrick, Ghonwa Ahmad, Audrey Wood et al.
The use of ketamine for the management of neuropsychiatric conditions outside clinical settings has rapidly expanded, creating a critical need to understand diverse individual experiences. We conducted a qualitative content analysis of posts from the r/TherapeuticKetamine subreddit. From 3302 threads, the 500 highest-engagement threads (12,852 comments) were analyzed by independent coders...
Journal of Clinical Psychopharmacology
March 24, 2026
Riccardo Guglielmo, Emma Laura Facchinetti, Daniele Cioci et al.
Treatment-resistant depression affects up to one third of patients with major depressive disorder and is frequently accompanied by persistent cognitive impairments that significantly hinder functional recovery. Emerging evidence suggests that sub-anesthetic esketamine does not appear to be associated with cognitive deterioration and may be associated with procognitive effects; however, no...
Biomolecules
March 24, 2026
Veronica Begni, Floriana de Cillis, Natascha Pfeiffer et al.
Pharmacological antidepressant treatments alter the molecular and functional reactivity of stress-sensitive neural networks. However, how classical versus rapid-acting antidepressants differentially modulate acute stress-induced transcriptional responses across brain regions remains unclear. Here, we compared imipramine and ketamine in mice exposed to acute swim stress, assessing...
Journal of psychopharmacology (Oxford, England)
March 21, 2026
Jesús García-Jiménez, D Nuñez-arias, G Carretero Merelo et al.
The trajectory and predictors of response under routine clinical care of esketamine nasal spray (ESK NS) over treatment-resistant depression (TRD) require elucidation. This retrospective, longitudinal cohort study was conducted across three Spanish centers. Adults diagnosed with TRD who initiated ESK NS and completed at least the induction phase were included. Assessments occurred at baseline,...
Nan fang yi ke da xue xue bao = Journal of Southern Medical University
March 20, 2026
Zhuoning Zhang, Xinyu Hao, Fuyang Cao et al.
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...
Journal of Psychoactive Drugs
March 20, 2026
Marina A. M. Portes, Leandro J Bertoglio
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...
Journal of the American Academy of Child and Adolescent Psychiatry
March 17, 2026
Yunjia Liu, Qiang Wang
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...
BMC Psychiatry
March 17, 2026
Bernhard T Baune, Kevin Rosemann, Dimitri Hefter et al.
2 citations
Intranasal esketamine: real-world clinical practice in treatment-resistant depression and factors associated with treatment response.
Biological Psychiatry
March 16, 2026
Xianglian Wang, Jing Xia, Heyi Luo et al.
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...
Cureus
March 14, 2026
Suneha Shelke, Rusheeth Thummalapally
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)...
Clinics and practice
March 13, 2026
Alessandro Guffanti, Matteo Leonardi, Natascia Brondino et al.
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...
Child and Adolescent Psychiatry and Mental Health
March 13, 2026
Marc-Antoine Crocq, Philippe Auby
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...
Neurochemical Research
March 13, 2026
Lan Luo, Miao Yu, Xiaodong Li et al.
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...
Int J Psychiatry Clin Pract
March 11, 2026
Michele Prato, Matteo Carminati, Filippo Frizzi et al.
1 citation
Fast-acting approaches for treatment-resistant depression: real-world comparative effectiveness of Intranasal Esketamine versus accelerated rTMS.
Pharmacological Reports
March 11, 2026
Benjamin D. Brody, Dora Kanellopoulos
1 citation
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...
Basic & Clinical Pharmacology & Toxicology
March 11, 2026
Chendi Zhao, Yang Wang, Jinglang Wu et al.
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...
bioRxiv (Cold Spring Harbor Laboratory)
March 10, 2026
Arina Nikitina, Christian Bustamante Toro, Raymond Gifford et al.
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...
CNS Spectrums
March 10, 2026
Halima Faisal, Gia Han Le, Angela T H Kwan et al.
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...
Annals of Clinical Psychiatry
March 10, 2026
Brian S. Barnett
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...