PharmacopsychiatryOctober 2, 2026Masami Murao, Daiki Setoyama, Yasuyuki Matsumoto et al.
Abstract This study investigated the antisuicidal effects of repeated intravenous ketamine in patients with treatment-resistant depression and explored associations between suicidal ideation and temporal changes in selected plasma biomarkers to identify potential biomarkers. This secondary analysis of an open-label trial included outpatients with treatment-resistant depression who received four...
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...
Fear and anxiety perform essential protective roles, yet when they become dysregulated, they can trap trauma survivors in persistent hypervigilance and distress. Post-traumatic stress disorder (PTSD) manifests as intrusive memories, avoidance, and heightened arousal long after the precipitating event. Although current pharmacotherapies - including selective serotonin reuptake inhibitors,...
As accumulating evidence suggests the antisuicidal properties of ketamine, elucidating its underlying mechanisms and predictors of treatment response has become crucial. Whether a combination of clinical markers can enhance the prediction of the antisuicidal response to ketamine remains unclear.Using data from our previous randomized placebo-controlled and open-label trials, this post hoc...
Serotonergic psychedelics, such as lysergic acid diethylamide, and psilocybin, and the entactogen 3,4-methylenedioxymethamphetamine exhibit agonist activity at the 5-hydroxytryptamine 2B receptor, a signalling pathway known to mechanistically mediate drug-induced valvular heart disease. This systematic review evaluates whether chronic or repeated use of psychedelics and...
PharmacopsychiatryJune 2, 2025Ludovic C Dormegny-Jeanjean, Suzie Lenoir, Ilia Humbert et al.1 citation
Ketamine and esketamine (ESK) offer new treatment options for resistant depression. Unlike traditional antidepressants, they can be used in combination with non-selective monoamine oxidase inhibitors (NS-MAOI) without the risk of serotonergic syndrome. However, potential sympathomimetic synergy may lead to elevated blood pressure (BP). This series investigates whether cardiovascular parameters...
Abstract Regulatory compliance is crucial in the clinical development of psychedelic substances, including psilocybin. This study aimed to examine the alignment of clinical trial protocols for psilocybin in the treatment of major depressive disorder (MDD) and treatment-resistant depression (TRD) with established regulatory requirements. A cross-sectional investigation was conducted on...
Low-grade inflammation (LGI) contributes to resistance against traditional antidepressants. However, whether the antidepressant and antisuicidal effects of ketamine on patients with treatment-resistant depression (TRD) differ between those with LGI and those without LGI remains unknown.This study included 167 patients with TRD, among whom 46 had LGI and 121 did not have LGI. The patients...
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...
Abstract Renewed interest in the effects of psychedelics in the treatment of psychiatric disorders warrants a better understanding of the neurobiological mechanisms underlying the effects of these substances. During the past two decades, state-of-the-art studies of animals and humans have yielded new important insights into the molecular, cellular, and systems-level actions of psychedelic...
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...
Abstract Introduction Psychedelics show promise in treating unipolar depression, though patients with bipolar disorder have been excluded from recent psychedelic trials. There is limited information on the use of classic psychedelics (e. g., LSD or psilocybin) in individuals using mood stabilizers to treat bipolar disorder. This is important to know, as individuals with bipolar depression may...
Psychedelics have shown great promise in modern clinical trials for treating various psychiatric conditions. As a transdiagnostic treatment that exerts its effects through subjective experiences that leave enduring effects, it is akin to psychotherapy. To date, there has been insufficient discussion of how psychedelic therapy is similar to and different from conventional psychotherapy. In this...
The renaissance of psychedelics has accelerated further over the past year. At least that’s true if you follow the public press. The New York Times recently titled “The Psychedelic Revolution Is Coming. Psychiatry May Never Be the Same.” on its front page 1.
Abstract Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), or dimethyltryptamine (DMT), as well as psychoactive drugs that trigger phenomenologically- related experiences like 3,4-methylenedioxymethamphetamine (MDMA) and ketamine, belong to the most promising treatment approaches in contemporary psychiatry. Psychedelic-assisted psychotherapy is not only a new...
Abstract Classical psychedelics, primarily psilocybin and lysergic acid diethylamide (LSD), have been used and extensively studied in Western medicine as part of substance-assisted psychotherapy in the 1950s and 1960s. Modern clinical research is currently gaining momentum and provides new evidence for the safety and efficacy of classical psychedelics (primarily psilocybin, but also LSD and...
Abstract Initial interest in the value of psychedelic drugs (“psychotomimetics”) in psychiatry began in the early 20th century, with explorations of the possibility that mescaline or peyote could produce psychosis-like effects. Over time, interest was focused on whether the effects of psychedelics could inform as to the underlying basis for psychiatric disorders. As research continued, and...
Over the last few years, hundreds of new psychoactive substances (NPS) have been identified in Europe. Apart from some herbal compounds, NPS mainly include synthetic cannabinoids and a range of new synthetic stimulants (e. g., cathinones). Synthetic NPS are often developed whilst modifying the basic chemical (e. g., phenethylamine or tryptamine) structure. Although the pharmacology and...
INTRODUCTION: Deficiencies in both vitamin B12 and folate have been associated with depression. Recently, higher baseline vitamin B12 levels were observed in individuals with bipolar depression who responded to the antidepressant ketamine at 7 days post-infusion. This study sought to -replicate this result by correlating peripheral vitamin levels with ketamine's antidepressant efficacy in...
Preclinical and clinical research suggests that the endogenous cannabinoid system is involved in cognitive impairments related to schizophrenia. In particular, deficient generation of mismatch negativity (MMN) indicating auditory sensory memory is a characteristic finding in schizophrenic patients. Experimental studies implicate deficient N-methyl-D-aspartate (NMDA) receptor functioning in such...
Background: Ketamine is a potent NMDA receptor antagonist with rapid antidepressant properties at subanaesthetic doses. This multimodal imaging study reveals the effects of a subanaesthetic ketamine infusion on fMRI-BOLD responses during an emotional processing task and their relationship to glutamatergic metabolite concentrations in the pregenual anterior cingulate cortex (PACC) assessed by...
Ketamine is a potent glutamatergic NMDA receptor antagonist with rapid antidepressant properties, thus providing a valuable research tool for the investigation of the neurobiology of major depressive disorder (MDD). Increasing evidence underscores the role of glutamate dependent neuroplasticity and glutamatergic neurotransmission and metabolism in the pathophysiology of MDD. This multimodal...
Misattribution of distorted self-generated speech in patients with schizophrenia has been associated with increased lateral temporal activation. As a pharmacological model of schizophrenia, we tested whether ketamine would induce the same effects in healthy individuals. Participants were 8 healthy male volunteers who were naïve to ketamine (mean age: 28 years). Ketamine (0.23 mg/kg bolus...
We tested the hypothesis that THC disrupts self-timed actions in healthy volunteers, and that this effect is related to self-rated perceptions of time distortion. We found that THC impaired subjective time perception and reduced the rate of button pressing, although the change in the rate of button pressing was more closely related to impaired concentration and intoxication. We conclude that...
We intended to assess safety, response to treatment and time to response of 1.25 mg/kg oral S-ketamine as add-on to standard antidepressants in four depressed patients. Two patients with melancholic depression responded early and stayed in remission, while two patients with distinct somatic symptoms, chronicity or atypical features did not respond. The limited number of patients does not allow...