Abstract Background Cognitive dysfunction is associated with impaired psychosocial functioning in patients with major depressive disorder (MDD). Patients with treatment-resistant depression (TRD) exhibit more pronounced cognitive dysfunction than those with non-resistant MDD, underscoring the need for effective therapeutic strategies. Psilocybin has emerged as a promising treatment for...
Abstract Background Despite sequential treatments with conventional antidepressants, many patients with depression experience insufficient clinical improvement, referred to as treatment-resistant depression (TRD). Psilocybin, a serotonergic psychedelic acting as a 5-HT2A receptor agonist, has attracted increasing attention as a novel treatment, with clinical trials demonstrating rapid and...
Abstract Background Psilocybin, a prodrug metabolized to psilocin, a serotonin 2A receptor agonist, has reemerged as a promising therapeutic option for treatment-resistant depression (TRD). Clinical trials conducted mainly in North America and Europe have demonstrated that psilocybin administered with psychological support can produce rapid and sustained antidepressant effects with favorable...
Abstract Background Despite recent advances in the treatment of major depression, approximately 30% of patients show insufficient improvement with conventional antidepressants, a condition commonly referred to as treatment-resistant depression (TRD). Psilocybin is a classic psychedelic compound that has received renewed attention as a promising therapeutic candidate for TRD. Clinical trials...
SchizophreniaAugust 31, 2026Nataliia Maronchuk, Jean Paul, Fabienne Post et al.
Abstract Background Delays in seeking help are common in schizophrenia and are associated with negative outcomes. In addition to structural barriers, there is growing evidence that subjective interpretations of psychotic experiences, including delusions, voices, and religious or spiritual attributions, play a crucial role in recognizing symptoms and seeking care. Objective This study explores...
Ketamine may alleviate treatment-resistant depression (TRD) primarily through glutamatergic modulation, with downstream dopaminergic activation. Iron plays an important role in monoaminergic metabolism, that is also implicated in the pathophysiology of TRD. Both Quantitative Susceptibility Mapping (QSM) and Effective Transverse Relaxation Rate (R2*) mapping can determine the extent of iron...
This systematic review and meta-analysis of six randomized controlled trials aimed to investigate the temporal changes in the efficacy and safety of psilocybin treatment for major depressive disorder (MDD). Separate meta-analyses were conducted for standard-dose psilocybin (25 mg/session, or 20-30 mg/70 kg/session) and low-dose psilocybin (10 mg/session or 15.05 mg/70 kg/session) subgroups....
Introduction: While the rapid and robust effects of ketamine on depressive symptoms in treatment-resistant depression (TRD) have been demonstrated, the influence of ketamine treatment on cognitive function has not yet been fully elucidated. We aimed to evaluate the effects of ketamine treatment on cognitive function as part of a study that investigated the efficacy of repeated ketamine...
BACKGROUND: Over the past decade, neuropsychopharmacology has shifted from stagnation to momentum, with first-in-class mechanisms and biomarker-enabled trials spanning psychiatry and neurology. METHODS: We narratively synthesized advances from 2013 to 2026 across central nervous system (CNS) discovery and development, including pivotal trials, regulatory actions, digital/real-world evidence,...
Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD. While glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) has been demonstrated to play crucial roles in the process of pharmacological action of ketamine in experimental animals, it remains elusive how ketamine exhibits...
Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review provides a comprehensive overview of psilocybin's history, recent clinical evidence, ongoing clinical trials, neuroimaging findings, and regulations. Historically used in spiritual and healing rituals, psilocybin was in the early 1970s subjected to...
Psychedelics are undergoing a clinical research renaissance, with compounds such as psilocybin advancing to Phase 3 trials for treatment-resistant depression and receiving fast-track or breakthrough designations from regulatory agencies. Despite this progress, the field lacks standardized terminology to guide clinical development, dosing, safety monitoring, and regulatory classification. Here,...
Approximately 30 % of patients with treatment-resistant depression (TRD) respond to ketamine; however, no replicable predictors of response have been reported. The imbalance between excitatory and inhibitory neurotransmissions may be implicated in the mechanism of action of ketamine. This study aimed to evaluate whether the ratio of glutamate and glutamine (Glx) to GABA levels at baseline in...
Abstract Background Only 18-45% of individuals with treatment-resistant depression (TRD) respond to intravenous ketamine therapy. Although some neurobiological predictors of response to ketamine have been reported, none have been consistently replicated across multiple studies. The imbalance between glutamatergic excitatory and GABAergic inhibitory neurotransmissions is implicated in the...
This study aims to investigate the acute and sustained antidepressant effects of repeated ketamine infusions in patients with treatment-resistant depression (TRD), and to identify early metabolomic changes predictive of treatment outcomes using metabolome analyses. This open-label study investigated the effects of four intravenous ketamine infusions (0.5 mg/kg) administered over 2 weeks in 30...
Abstract Background Whereas ketamine has displayed robust antidepressant effects in treatment-resistant depression (TRD) (Han et al., 2016), only 30-40% of patients with TRD respond to ketamine therapy (Wilkinson et al., 2018; Sakurai et al., 2020). Several postmortem studies have shown decreased myelination in patients with depression (Hamidi, Drevets and Price, 2004; Altshuler et al., 2010),...
Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were...
Abstract Introduction The therapeutic potential of psychedelics for various mental disorders has gained significant interest. Previous studies have highlighted that psychedelics induce psychoactive effects, including challenging aspects of experiences. These experiences are assessed using the Challenging Experience Questionnaire (CEQ), yet its Japanese version has been unavailable. This study...
Abstract Introduction Psychedelics have garnered increased attention as potential therapeutic options for various mental illnesses. Previous studies reported that psychedelics cause psychoactive effects through mystical experiences induced by these substances, including an altered state of consciousness. While this phenomenon is commonly assessed by the Mystical Experiences Questionnaire...
Abstract Aim Psychedelics have recently gained attention as potential therapeutic agents for various psychiatric disorders. Previous research has highlighted that a diminished sense of self, commonly termed “ego‐dissolution” is a pivotal feature of the psychedelic‐induced state. While the Ego‐Dissolution Inventory (EDI) is a widely acknowledged instrument for measuring this phenomenon, no...
In recent years, there has been a growing movement to apply psychedelic drugs for treating psychiatric disorders, including depression. Although the therapeutic effects of psychedelic drugs were verified in the 1960s, their abuse by the public led to their designation as narcotics in 1970, and clinical research on them was suspended for a time. However, since 1994, clinical trials have been...
Abstract Introduction Predictors of treatment response to intravenous ketamine remain unclear in patients with treatment-resistant depression (TRD); therefore, this study aimed to clarify these predictors using the US National Institutes of Health database of clinical trials. Methods Data from a placebo-controlled, double-blind, randomized controlled trial were used to assess the efficacy of...
In recent years, it is common for a single drug to be developed for multiple diseases almost simultaneously, e.g., pimavanserin and psilocybin. Although there was gloomy news for the field of neuropsychopharmacology, such as withdrawal of the world's leading mega-pharmaceutical companies from the development of CNS drugs, drugs based on novel mechanisms of action have been investigated. This is...
Abstract Introduction There is an imminent need for faster-acting and more effective antidepressants beyond the monoaminergic hypothesis. Methods We systematically searched the US Clinical Trials registry for antidepressant compounds with completed phase II and III trials. Compounds that demonstrated significant superiority over placebo in the primary outcome measure in the latest phase of...