The purpose of this study is to assess the effects of 5-HT1A receptor blockade on the acute subjective effects of psilocybin, as measured through subjective survey measures and acute electroencephalography (EEG). Further, the investigators will assess the effects of psilocybin on post-acute sleep and dreaming through the use of sleep EEG and sleep and dream ...
BACKGROUND: Major depressive disorder is one of the most debilitating psychiatric disorders worldwide. First-line treatments such as selective serotonin reuptake inhibitors have significant limitations, including delayed onset of therapeutic effects and treatment resistance in about 30% of patients. Increasing evidence suggests that acute administration of s...
Psychedelics show therapeutic potential for treating psychiatric disorders. While studies have emphasized the roles of cortical pyramidal cells, GABAergic neurons also express serotonin receptors and are therefore likely targets of psychedelics. In this study, we determine the effect of psilocybin on the activity dynamics of major GABAergic cell types in the...
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily for recreational purposes, the molecular mechanisms underlying its actions remain incompletely understood. Here, we examined the acute effects of psilocin, the active metabolite of psilocybin, on excitatory neuro...
BACKGROUND: The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmissi...
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could promptly alleviate both conditions remains unclear. Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia and anxiodepression-li...
BackgroundMajor depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-H...
BACKGROUND AND AIMS: Drug discrimination procedures have made important contributions to the pre-clinical investigation of psychedelic drugs, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). One of the most important being to highlight the critical role of central 5-HT2A rece...
Conventional antidepressants show moderate efficacy in treating major depressive disorder. Psychedelic-assisted therapy holds promise, yet individual responses vary, underscoring the need for predictive tools to guide treatment selection. Here, we present graphTRIP (graph-based Treatment Response Interpretability and Prediction) - a geometric deep learning a...
OBJECTIVE: Psychedelics are able to trigger highly intense and profound alterations in self-consciousness, perception, affective, and cognitive processes. Indeed, recent studies show that ketamine and psilocybin could be used as fast-acting antidepressants. However, the molecular and neurochemical mechanisms of these psychedelics and their actions at the lev...
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...
Epilepsy, a chronic neurological disorder affecting around 65 million people globally, is characterized by recurrent, unprovoked epileptic seizures. Psilocin, the active metabolite of psilocybin, a well-known psychedelic compound, has recently gained attention for its potential antidepressant and anxiolytic properties. This study aims to investigate the anti...
Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three h...
Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders1-3. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT2A (ref. 4). However, 5-HT1A also plays a part in the beha...
ABSTRACT A variety of classic psychedelics and MDMA have been shown to enhance fear extinction in rodent models. This has translational significance because a standard treatment for posttraumatic stress disorder (PTSD) is prolonged exposure therapy. However, few studies have investigated psilocybin’s potential effect in fear learning paradigms. More specific...
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plaus...
Serotonergic psychedelics have been identified as promising next-generation therapeutic agents in the treatment of mood and anxiety disorders. While their efficacy has been increasingly validated, the mechanism by which they exert a therapeutic effect is still debated. A popular theoretical account is that excessive 5-HT2a agonism disrupts cortical dynamics,...
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plaus...
Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT2A receptors, found predominantly in cortical regions. By interacting with these receptors, serotonergi...
Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three h...
