Supplement 1. Additional tables presenting primary and secondary outcomes, sensitivity analyses, and exploratory findings. Table A1. ITT analyses for QIDS-SR-16 and MBI-HSS-MP. Table A2. Adjusted ITT analyses for QIDS-SR-16 and MBI-HSS-MP. Table B1. Intent-To-Treat (ITT) Analysis for Demoralization Scale (DSII) and PTSD Checklist for DSM-5 (PCL-5). Table B2....
Serotonergic psychedelics have shown promise in clinical trials for treating an array of mental health disorders, including depression, anxiety, and post-traumatic stress disorder. Despite these findings, our understanding of how these drugs mechanistically exert their therapeutic effects remains incomplete. While researchers have regularly employed rodent p...
Introduction In recent years, psychiatry has witnessed a renaissance in the investigation of psychedelic compounds, a broad class of psychoactive substances that induce altered states of consciousness, often characterized by changes in perception, mood, and cognition, which were largely shelved following regulatory crackdowns in the 1970s. The renewed intere...
Major depressive disorder (MDD) is a complex and debilitating condition affecting approximately 280 million people worldwide. Its heterogeneous nature makes it difficult to establish clinical treatment guidelines that address individual differences in treatment response. As a result, many individuals experience treatment-resistant depression (TRD) failing to...
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease...
Introduction: Psilocybin, a serotonergic psychedelic, has shown therapeutic potential in treating mental health disorders by, amongst the many effects, promoting neuroplasticity and reorganising functional connectivity across cortical and subcortical networks involved in emotion and cognition. Veterans with traumatic brain injuries (TBI) often experience chr...
Abstract Background Major depressive disorder (MDD) is a multifactorial and heterogeneous disorder that affects around 280 million individuals worldwide, with approximately 80 million experiencing treatment-resistant depression (TRD). Neuronal hypotrophy and axon hypomyelination in the prefrontal cortex (PFC) are hallmark features of MDD, highlighting the ne...
Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death - factors that contribute to the development of neurological and psychiatric dis...
Introduction: Many Veterans who experienced blast-related traumatic brain injuries (TBIs) in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop chronic cognitive and PTSD-related behavioral traits tha...
Depression and anxiety are disabling and high incidence mental disorders characterized by phenotypic heterogeneity. Currently available treatments show severe limitations. Thus, there is an urgent need for effective treatments in this population. In the search for novel rapid-acting antidepressants, the psychedelic psilocybin has emerged as a promising thera...
Abstract Major depressive disorder (MDD) is a leading cause of disability that affects over 300 million people globally. Despite multiple antidepressant trials, approximately one-third of MDD patients remain symptomatic, progressing to treatment-resistant depression (TRD). This persistence possibly is due to the multifaceted etiology of TRD, encompassing bio...
Psychiatric disorders are marked by habitual patterns of thought, emotion, and behavior, and many mental health disorders are resistant to standard treatments (1)(2)(3)(4). For example, symptoms of major depressive disorder include ruminative negative thoughts, pervasive sadness, and lack of goaldirected behavior (5)(6)(7). Similarly, many anxiety and trauma...
Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to the biosynthesis of psilocybin can enhance its production process. In this study, we elucidate the ...
Brain aging (BA) processes are complex, often affect multiple systems, and frequently lead to cognitive decline and increased susceptibility to insults. BA appears to be a primary risk for the development of many prominent neurodegenerative pathologies. The US Census Bureau predicts that the aging population (65+) will represent a greater proportion of the U...
Psychedelic drugs, known for their perception-altering properties, are gaining popularity in the treatment of mental health and pain disorders. As exploratory studies demonstrate clinical efficacy with few adverse events, it is expected that more patients will ingest psychedelic drugs. For therapeutic reasons, as with any drug, anaesthesiologists must be awa...
Irritable bowel syndrome (IBS) is prevalent and can be disabling. Many patients remain symptomatic despite behavioral and medical therapies. Psychedelic-assisted therapy (PAT), in which serotonergic agents like psilocybin are administered in a psychotherapeutic context, has shown promise for refractory psychiatric disorders, including major depressive disord...
Abstract Background Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through the serotonin 5-HT2A receptor (5-HT2A). Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. Aims...
BACKGROUND: Posttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches. Preliminary evidence sup...
Chronic stress exerts profound effects on mental health, contributing to disorders such as depression, anxiety, and cognitive impairment. This study examines the potential of psilocybin to alleviate behavioral despair and cognitive deficits in a rodent model of chronic stress, focusing on the interplay between the Hypothalamic-Pituitary-Adrenal (HPA) axis an...
Known for their capacity to alter perception and consciousness, psychedelics are increasingly being explored for therapeutic applications in treating conditions such chronic pain, major depressive disorder, and post-traumatic stress disorder.1,2 Despite historical stigmas and legal restrictions, recent changes in legislation and the United States Food and Dr...