The use of psychedelic substances such as LSD, psilocybin, and dimethyltryptamine is currently being re-evaluated for their therapeutic potential in psychiatry. While international clinical research had started in the 2010s, France only initiated its first psychedelic trials in 2024. This study aimed to explore the knowledge, perceptions, and attitudes of French mental health professionals...
Abstract Negative emotional bias, including reduced processing of positive information and negative interpretation of ambiguous stimuli, is a core feature of depression. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist with rapid antidepressant effects in treatment-resistant depression (TRD), reduces depressive symptoms, but its effects on distinct components of emotional...
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT), have re-emerged as promising treatments for psychiatric conditions linked to suicidality. However, rare reports of increased suicidality potentially associated with psychedelic use have raised safety concerns. This article examines the complex relationship between psychedelics and...
Regulatory approvals for intranasal esketamine in treatment-resistant depression (TRD) differ with respect to its indication for suicidal ideation. While rapid antidepressant effects are well documented, whether esketamine exerts an anti-suicidal effect independent of mood improvement remains unclear. In this two-center observational study, 261 adults with moderate-to-severe TRD at Sainte-Anne...
Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression increase the risk of treatment-resistant depression (TRD), with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for TRD, but its efficacy on comorbid TRD-PTSD remains...
medRxiv Preprint ServerMarch 31, 2026Maia 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...
Ketamine is an NMDA-receptor antagonist, which alters the state of wakeful consciousness at high doses. At lower doses, it induces reversible psychotic-like symptoms and has been used as a pharmacological model of psychosis. In this study, we explore whether low doses of ketamine disrupt conscious access in relation with its psychotomimetic effects, and investigate the neural correlates of its...
Abstract Disruption of conscious access contributes to the advent of psychotic symptoms in schizophrenia and could also explain lack of insight in other psychiatric disorders. In this study, we explored how insight and psychotic symptoms related to disruption of consciousness in obsessive-compulsive disorder (OCD) and schizophrenia, respectively. Patients with schizophrenia, and patients with...
Psilocybin is a psychedelic serotonergic compound that is renowned for its potent psychoactive effects. Over the past 15 years, an increasing number of controlled clinical trials showed that it has a fast-acting and sustainable efficacy in treating various psychiatric disorders. Neuroimaging studies have been conducted with the objective of elucidating the neurobiological mechanisms underlying...
Deficits in working memory (WM) are a hallmark of neuropsy-chiatric disorders such as schizophrenia, yet their neurobiological basis remains poorly understood. Glutamate N-methyl-D-aspartate receptors (NMDARs) are critical for spatial WM (sWM), with NMDAR antagonist ketamine known to attenuate task-evoked activation and reduce sWM accuracy. Cortical microcircuit models hypothesize that NMDAR...
Precision psychiatry aims to identify markers of interindividual variability that allow for predicting the right treatment for each patient. However, bridging the gap between molecular-level manipulations and neural systems-level functional alterations remains an unsolved problem in psychiatry. After decades of low success rates in pharmaceutical research and development for psychiatric drugs,...
Introduction: Major depressive disorder (MDD) is more likely to resist to usual treatment when it is associated with post-traumatic stress disorder (PTSD). Capitalizing on the effect of ketamine in both treatment-resistant depression (TRD) and PTSD, we conducted a study in order to assess the efficacy of intranasal (IN) Esketamine in patients having TRD with comorbid PTSD. Materials and...
Psychedelics are powerful psychoactive substances. Natural psychedelics have been used for millennia by human civilizations, in particular in Latin America, while synthetic psychedelics were discovered in the 50s, giving rise to a lot of research before they were prohibited. More recently, their therapeutic properties have been studied especially to help patients with psychiatric conditions,...
According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural...
Previous research suggests that the conscious perception of a masked stimulus is impaired in schizophrenia, while unconscious bottom-up processing of the same stimulus, as assessed by subliminal priming, can be preserved. Here, we test this postulated dissociation between intact bottom-up and impaired top-down processing and evaluate its brain mechanisms using high-density recordings of...