Psychedelics represent a potential breakthrough for treatment-resistant depression; however, the prolonged in-clinic monitoring required for compounds such as psilocybin and lysergic acid diethylamide is a logistical hurdle to widespread use. Intranasal mebufotenin (5-methoxy-N,N-dimethyltryptamine), a 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2A agonist associated with brief psychedelic...
Background/Objectives: Treatment-resistant depression (TRD) is heterogeneous and recurrent. Psilocybin administered with structured psychological support can reduce symptoms rapidly. Support protocols differ in content and intensity, and trial design complicates estimates of the specific drug effect and durability. We reviewed efficacy, durability, mechanisms, safety, and clinical delivery in...
Introduction Generalized anxiety disorder (GAD) is a chronic, disabling condition for which currently available pharmacotherapies have delayed onset, incomplete remission rates, treatment-emergent adverse effects and substantial real-world discontinuation. DT120, formerly MM120, is an investigational orally disintegrating tablet formulation of lysergide tartrate being developed as a single-dose...
Objective: To synthesize evidence for intravenous racemic ketamine and regulated intranasal esketamine in adults with acute suicidal presentations; distinguish the outcomes these interventions have and have not been shown to change; and place any rapid response within a complete emergency suicide-care pathway. Methods: A narrative review of PubMed/MEDLINE-indexed literature was updated through...
This qualitative study examines self-reported experiences with 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) shared on Reddit to explore subjective reports, contextual influences, and perceived effects. A total of 120 posts from 24 discussion threads were purposively selected and thematically analyzed using an inductive, constructivist approach. The analysis resulted in 48 codes, which were...
Objectives Ketamine and esketamine are increasingly used for treatment-resistant depressive disorders, particularly when rapid symptom reduction is clinically desirable. Intranasal esketamine has a product-specific regulatory framework in several jurisdictions, whereas most racemic ketamine formulations remain off-label for psychiatric indications. This narrative review provides practical...
Major depressive disorder (MDD) and treatment-resistant depression (TRD) continue to drive interest in ketamine-family compounds and psilocybin, but antidepressant efficacy alone does not establish whether these interventions can be evaluated reliably or implemented responsibly. We conducted a structured narrative review using targeted PubMed/MEDLINE searches through 21 July 2026,...
ABSTRACT Psychedelic compounds exhibit diverse pharmacological and clinical effects, underscoring the need for further research and the development of clear guidelines to support their safe and effective clinical use. Growing interest in psychedelics has also increased attention toward the relationship between nutrition, dietary habits, and psychiatric disorders. This narrative review presents...
This study evaluated the acute and short-term effects of repeated ketamine treatment on appetite in adult inpatients with treatment-resistant mood disorders, including major depressive disorder and bipolar disorder. Appetite, hunger, and desire to eat were assessed using the Visual Analog Scales (VAS) and the Simplified Nutritional Appetite Questionnaire (SNAQ) at baseline and at multiple time...
Anhedonia, a core symptom of major depressive disorder (MDD), is associated with illness severity, suicide risk, poor functioning, and predicts poor response to antidepressants. While no treatments are approved, ketamine and esketamine show promise in reducing anhedonia. This study examines clinical and sociodemographic features linked to anhedonia treatment response in treatment-resistant...
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...
Approximately 30% of patients treated for major depressive disorder develop treatment-resistant depression (TRD). The STAR*D study demonstrated remission rates decline progressively with each antidepressant failure (37%, 31%, 14%, and 13%, respectively). A single-day individualized dosing regimen of GH001 (synthetic mebufotenin for inhalation) produced rapid, large improvements in depressive...
Optimising patient outcomes in treatment resistant depression (TRD) requires treatments which provide sustained remission, without relapse, and tolerability in the long term. ESCAPE-LTE (NCT04829318) was a phase IV, single-arm, 2-year (104 weeks) long-term extension of ESCAPE-TRD (NCT04338321; 32 weeks), a rater-blinded, randomised, active-controlled trial, which evaluated the safety,...
Introduction Research on psychedelic compounds has grown quickly in the past decade. Yet molecule-specific, quantitative summaries are scattered, making it hard to see how interest differs by compound or over time. Objectives To quantify PubMed-indexed publications on ketamine, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), psilocybin, and psilocin; to describe annual trends...
To explore sex, racial and ethnic disparities in esketamine clinical trials for mental health disorders registered on ClinicalTrials.gov. We conducted a registry-based cross-sectional analysis of interventional esketamine trials with results posted on ClinicalTrials.gov (cut-off date: 10 February 2025). Using predefined eligibility criteria, two investigators independently extracted and...
Treatment-resistant depression (TRD), a persistent condition impacting up to 30% of patients with major depressive disorder, carries substantial personal and economic burden. There remains an unmet need for therapies that provide both rapid and durable improvements in TRD. Preliminary clinical trials indicate that GH001, a synthetic, inhalable formulation of mebufotenin, has the potential for...
Introduction MDMA (3,4-methylenedioxymethamphetamine)–assisted therapy has gained growing scientific attention as a potential treatment for post-traumatic stress disorder and other mental health conditions. Although clinical studies suggest potential benefits, concerns remain regarding cardiovascular safety, methodological rigor, and variability in psychotherapeutic support (Singh et al . CNS...
Background: Treatment-resistant depression (TRD) poses a significant therapeutic challenge, with remission often unattainable. Recognition and detection of treatment-emergent adverse events (TEAEs) are essential, as these events may significantly influence the quality of treatment response. This knowledge aids in personalizing care and selecting the best treatment strategy. Methods: In a...
Importance: Few pharmacotherapies are approved for treatment-resistant depression, and many patients do not achieve remission following treatment with those therapies. Objective: To examine the efficacy and safety of single-day treatment with a synthetic formulation of inhaled mebufotenin (GH001) vs placebo in patients with treatment-resistant depression. Design, Setting, and Participants: This...
Abstract Aim of study: The antidepressant effect of ketamine may be at least partly due to its antioxidant activity. The aim of the study was to assess whether ketamine develops a protective effect on HT22 neuronal cells under conditions of oxidative stress (OS) induced by hydrogen peroxide (H 2 O 2 ). Material and methods The experiment was performed on an immortalized mouse hippocampal HT22...
Treatment-resistant depression (TRD) poses a serious challenge to psychopharmacology, as many patients do not achieve remission despite available therapies. The persistence and recurrence of the disease in the absence of response to antidepressant treatment highlight the complex and multifactorial nature of the disease, including the dysregulation of biological processes such as oxidative...
Psilocybin-assisted therapies are increasingly studied for Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD), and methodological rigor requires both pharmacological evaluation and consistent reporting of non-pharmacological variables that influence therapeutic outcomes. To address this need, the ReSPCT (Reporting of Setting in Psychedelic Clinical Trials) guidelines were...
Treatment-resistant depression (TRD) and bipolar depression (TRBD) are severe, heterogeneous mood disorders associated with substantial functional impairment, elevated suicide risk and persistent unmet treatment needs. While pharmacological and psychological interventions continue to advance, many patients experience delayed, partial or unsustained benefit, underscoring the need for therapies...
Anhedonia is a key symptom of bipolar depression and a target of ketamine's rapid antidepressant effects. However, many patients with treatment-resistant bipolar depression (TRBD) do not respond. This study aimed to identify clinical and sociodemographic characteristics that are associated with nonresponse of anhedonia following short-term ketamine treatment in TRBD. A retrospective analysis...
Treatment-resistant depression (TRD) remains a significant public-health challenge, with many patients failing to respond to conventional therapies. Ketamine has emerged as a rapid-acting intervention, but quantitative outcomes alone do not capture patients' lived experiences, which shape engagement, acceptability, and adherence. We conducted a narrative review of qualitative and mixed-methods...