Background: Observational studies with ritual ayahuasca users suggest that experienced users tend to have better cognitive performance, while novice users may experience transient impairments, particularly in working memory. However, no randomized clinical trials have systematically evaluated the cognitive effects of ayahuasca in healthy volunteers. Procedures: This double-blind, randomized,...
Background: Depressive and anxiety symptoms are highly prevalent among patients with cancer and are associated with substantial reductions in quality of life. However, effective therapeutic options remain limited. Ayahuasca, a serotonergic psychedelic traditionally used in Amazonian ritual contexts, has shown rapid antidepressant and anxiolytic effects following a single administration in...
Growing evidence links inflammation with major depressive disorder (MDD) and treatment resistance. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a simple peripheral marker of systemic inflammation and immune balance and it may capture clinically meaningful heterogeneity in inflammatory burden, potentially contributing to variability in antidepressant response and vulnerability to...
Treatment-resistant depression affects up to one third of patients with major depressive disorder and is frequently accompanied by persistent cognitive impairments that significantly hinder functional recovery. Emerging evidence suggests that sub-anesthetic esketamine does not appear to be associated with cognitive deterioration and may be associated with procognitive effects; however, no...
PURPOSE/BACKGROUND: Chronic insomnia causes malaise and is associated with depression, irritability, cognitive impairment, impaired alertness, and substance abuse. Individuals with posttraumatic stress disorder (PTSD) often have both inadequate and fragmented sleep, putting them at elevated risk for these consequences. Sleep abnormalities in patients with PTSD include frequent trauma-related...
Treatment-resistant depression (TRD), a clinical subtype of major depressive disorder (MDD), is associated with greater severity and functional impairment, representing a significant challenge in psychiatric care. Recent studies suggest that the use of psychedelics can provide rapid and substantial improvement in the severity of depressive symptoms. Therefore, the aim of this systematic review...
Purpose/Background: The therapeutic effects of psilocybin treatment are thought to be influenced by the subjective dose-dependent psychedelic experience, as well as the individual participant’s mindset and the treatment environment. However, the relative contribution of an individual’s pretreatment clinical characteristics and their subjective psychedelic experience remains unclear. We examined...
Purpose: Treatment-resistant depression (TRD) is a common phenomenon and a considerable clinical challenge; recently, esketamine in conjunction with an oral antidepressant (AD) has emerged as a potential treatment for TRD. Several studies have shown the efficacy of esketamine in improving depressive symptoms. This prospective study aims to explore the long-term effects of esketamine therapy on...
Maintenance intravenous racemic ketamine therapy demonstrated significant, persistent, and broad efficacy for treatment-resistant depression as demonstrated by reductions in Montgomery-Åsberg Depression Rating Scale and Patient-Health Questionnaire-9 total scores and equivocal changes in every item on both rating scales. The magnitude of change in individual items was similar to that of...
This study is the first to formally evaluate in humans the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RE104, a prodrug of the synthetic psychedelic known as 4-hydroxy-N,N-diisopropyltryptamine or 4-OH-DiPT. This double-blind, randomized, placebo-controlled, phase 1 study of single subcutaneous (SC) doses of RE104 (5 to 40 mg) included 6 cohorts and a total of 48...
Abstract: Background: Approximately one third of individuals with major depressive disorder have treatment-resistant depression (TRD). Glutamatergic modulators such as the N-methyl-d-aspartate receptor antagonist ketamine have rapid and robust antidepressant effects, but their use has been limited by accessibility and route of administration. This open-label pilot study assessed the adjunctive...
Abstract Background Preclinical evidence indicates that the κ-opioid receptor (KOR)/dynorphin pathway is implicated in depressive-like behaviors. Ketamine is believed to partly exert its antidepressant effects by modulating the opioid system. This post hoc study examined the following research questions: (1) at baseline, were there differences in KOR or dynorphin plasma levels between...
Departments of Psychiatry and Behavioral Neurosciences and Anesthesiology, Wayne State University, Detroit, MI [email protected] Received August 19, 2022; accepted after revision August 29, 2022. The author declares no conflicts of interest. There was no funding provided for this work. A podcast discussing this article is available online at the journal website.
Abstract Background Among the renewed applications of psychedelic medicines in psychiatry, 3,4-methylenedioxymethamphetamine (MDMA)–assisted therapy for posttraumatic stress disorder (PTSD) has demonstrated the most promise in early small-scale studies. Recent exploratory analyses from prior clinical trials of MDMA-assisted therapy for PTSD have suggested that recent use of selective serotonin...
Abstract Background Some staging models for treatment-resistant depression (TRD) have been developed in the attempt to predict treatment outcome, in particular with electroconvulsive therapy. However, these models have not been tested in predicting clinical outcome of ketamine treatment. We assessed the relationship between patients' classification with different TRD staging models and...
BACKGROUND: Although δ-9-tetrahydrocannabinol (THC), the main cannabinoid from the cannabis plant, is responsible for the psychotomimetic effects of cannabis, cannabidiol (CBD), the second most abundant cannabinoid in the cannabis plant, does not show any psychotomimetic effect. Cannabidiol has even been proposed to be antipsychotic and to counteract some of the psychotomimetic effects of THC....
Department of Psychiatry & Behavioral Health Stony Brook University Stony Brook, NY [email protected]. Department of Psychiatry & Behavioral Health Stony Brook University Stony Brook, NY. Received January 6, 2021; accepted after revision March 2, 2021.
Abstract Background Ayahuasca is a classic hallucinogen with anxiolytic and antidepressive properties. Anecdotal evidence also suggests that it improves performance (eg, singing, speech). This controlled trial assessed the effects of ayahuasca on speech performance and anxiety in individuals with social anxiety disorder. Methods Seventeen volunteers with social anxiety disorder participated in...
Abstract Background The recognition of emotions in facial expressions (REFE) is a core aspect of social cognition. Previous studies with the serotonergic hallucinogens lysergic acid diethylamide and psilocybin showed that these drugs reduced the recognition of negative (fear) faces in healthy volunteers. This trial assessed the acute and prolonged effects of a single dose of ayahuasca on the...
Abstract Purpose/Background This study was devised to compare the antidepressant and antisuicidal effects of oral and intramuscular (IM) ketamine versus electroconvulsive therapy (ECT). Methods/Procedures In our pilot study, 45 patients with major depressive disorder (based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria) in the age range of 18 to 70 years who...
To the Editors: N agele et al 1 have suggested medical utility of nitrous oxide (N2O) for the management of treatment-resistant major depression disorder (trMDD). Their work described basic concepts in N2O administration for the lay psychiatrist as well as the compound's known pharmacology and potential risks from repeated exposure, including N2O-induced inactivation of cobalamin and folate...
PURPOSE/BACKGROUND: Major depressive disorder (MDD) and obesity commonly co-occur. We sought to assess the impact of body mass index (BMI) on the acute antidepressant effects of ketamine in patients with treatment-resistant depression. METHODS/PROCEDURES: Post hoc analyses were conducted from a multisite, randomized, double-blind, placebo-controlled trial designed to assess the rapid-onset...