Journal of Psychoactive DrugsJuly 3, 2026Miguel Joaquim Soares Teles Couceiro, Victor José da Conceição Teixeira Amorim Rodrigues, Nuno Manuel Correia Torres
This case study explores the potential role of mystical-type experiences in ketamine-assisted psychotherapy (KAP). A patient with generalized anxiety disorder and migraines underwent four intramuscular KAP sessions (0.5-0.9 mg/kg). Outcomes were assessed using the Outcome Questionnaire-45 (OQ-45), the Hood Mysticism Scale (HMS), and interviews. Greater therapeutic gains followed sessions with...
Objective This study evaluated whether intramuscular (IM) ketamine is non‐inferior to intranasal (IN) esketamine for treatment‐resistant depression (TRD) and assessed differences in safety and healthcare costs. Methods In a retrospective, observational sequential cohort at the VA San Diego, 179 Veterans with TRD received eight treatments of either IN esketamine ( n = 89) or IM ketamine ( n =...
Ketamine promotes spine growth on the apical dendrites of pyramidal neurons in the prefrontal cortex (PFC), which are critical for its behavioral effects. Follow-up studies show that brain-derived neurotrophic factor (BDNF) signaling is critical for these effects. In this context, we sought to determine if microglial BDNF contributes to the synaptic and behavioral effects of ketamine....
OBJECTIVES To describe a case of ketamine-induced cystitis (KIC) in a middle-aged patient using ketamine recreationally, highlight diagnostic pitfalls that may lead to unnecessary antibiotics, and offer pharmacist-focused recommendations for assessment and management, including a formal causality assessment using the Naranjo algorithm. CASE SUMMARY A 56-year-old male with escalating...
Objective To investigate the effects of sub-anesthetic dose esketamine on oxidative stress markers and postoperative delirium(POD)in patients undergoing laparoscopic radical resection for colorectal cancer, so as to provide a reference for the selection of clinical anesthesia regimens. Methods A total of 201 patients who underwent radical resection for colorectal cancer at Taizhou People 's...
In this paper, which is in part intended as a speculative provocation and which combines philosophy of science, clinical practice and psychedelic therapy in a novel manner, we examine ketamine-assisted psychotherapy (KAP) through the lens of an expanded model of enactive cognition. While much work within both KAP and psychedelic-assisted therapy (PAT) in general has relied upon broadly...
Treatment-resistant depression (TRD) is associated with severe depression, low quality of life (QoL) and reduced work productivity, which may increase risk of relapse, suicide and suboptimal response to treatment. Esketamine nasal spray plus a newly-initiated oral antidepressant (esketamine+OAD) has been shown to improve depression symptoms, QoL and productivity in patients with TRD; however...
ABSTRACT: Introduction Ketamine and esketamine have reemerged as promising interventions for treatment-resistant depression (TRD), yet debate persists regarding the clinical relevance of acute dissociative experiences. This secondary exploratory analysis examined the relationship between dissociative experiences induced by subcutaneous esketamine and antidepressant response in patients with...
Neuroinflammation, particularly Toll-like receptor 4 (TLR4)-mediated signaling, plays a critical role in the pathophysiology of depression. This study aimed to investigate the mechanisms by which S-ketamine (S-ket) and S-hydroxynorketamine (S-HNK) modulate TLR4 and peroxisome proliferator-activated receptor alpha (PPARα) signaling in the prefrontal cortex (PFC) to exert antidepressant effects....
Over the past two decades, ketamine has emerged as a rapid-acting antidepressant, especially among patients with treatment-resistant depression. As an N-methyl-d-aspartate glutamate receptor antagonist, ketamine has reshaped the understanding of the underlying neurobiological mechanisms of depression treatment. Ketamine induces a transient state of enhanced neuroplasticity and likely...
Abstract Aim Ketamine is increasingly used for treatment-resistant depression, bipolar disorder, PTSD, chronic pain, and other psychiatric conditions[8,9]. As more adults receive serial ketamine infusions or intranasal esketamine, perioperative considerations with ongoing NMDA-receptor modulation. However, perioperative guidance remains limited, creating uncertainty around anesthetic dosing,...
INTRODUCTION: Ketamine, initially developed as an anesthetic and now increasingly prescribed for treatment-resistant depression, is also widely misused in recreational contexts. Chronic ketamine use, often leading to dependence, has been associated with severe physical complications, including ulcerative cystitis and gastrointestinal dysfunction, as well as cognitive, affective, and psychotic...
Psychiatric ServicesJuly 1, 2026Joshua Mitchell, Benjamin Bregman, Renuka Surujnarain et al.
Aided by COVID-19-era regulatory flexibilities, direct-to-consumer telemedicine has expanded access to mental health care. Ketamine prescribed off-label for psychiatric conditions is increasingly marketed online and delivered at home through telehealth platforms. Taking a wrongful death lawsuit against a telehealth ketamine provider as a point of departure, the authors examine how combining...
Ketamine analogues are emerging dissociative substances structurally related to ketamine and increasingly detected on drug markets worldwide. This study aimed to characterize patterns of use, user profiles, and associated health outcomes in France. We conducted a retrospective analysis of cases involving ketamine analogues reported to the French Addictovigilance Network up to 31 December 2024....
Oral administration of (S)-ketamine for treatment-resistant depression (TRD), as alternative to the registered intranasal or off-label intravenous administrations, has high potential. However, it is characterized by an extensive first-pass metabolism, resulting in low (S)-ketamine exposure and high levels of active metabolites, including (S)-norketamine and (S)-hydroxynorketamine. The relative...
Subanesthetic doses of ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, produce rapid and robust antidepressant effects in patients with treatment-resistant depression (TRD). However, after a single administration, the therapeutic benefit is short-lived, and strategies to maintain its efficacy remain unclear. This study focused on the glutamate...
Introduction Treatment-resistant major depressive disorder with high-risk suicidal ideation is a psychiatric emergency that requires rapid and effective intervention. Although intranasal esketamine and intermittent theta-burst stimulation (iTBS) are time-efficient therapeutic options, clinical reports describing their combined use in an accelerated inpatient schedule are limited, particularly...
Ketamine responses vary across patients and sessions, suggesting that dose alone is an incomplete organizing principle. We propose a state-first Gate-Amplifier-Reintegration framework in which awake low-dose ketamine acts primarily as an Amplifier of transient network flexibility, whereas autonomic-salience stability is treated as a candidate Gate that may shape whether this flexibility remains...
Perioperative depressive symptoms (PDSs) are common among patients who undergo major surgery and can lead to worse clinical outcomes. Esketamine has been reported to alleviate PDSs in patients undergoing certain types of surgery. However, there is a lack of evidence from large-scale, multisurgery studies to support its therapeutic effects in individuals with preexisting moderate-to-severe PDSs....
Treatment-resistant depression (TRD) represents an unmet challenge, accounting for disproportionate morbidity, disability, and healthcare burden in depression. Limitations of monoaminergic antidepressants have prompted a conceptual shift toward models emphasizing impaired neuroplasticity, synaptic dysfunction, and network dysregulation. This expert review synthesizes preclinical, translational,...