Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, females remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex differences across multiple...
Neuroplasticity, the brain's capacity to reorganise its structure and function, is a transdiagnostic feature across psychiatric and neurodegenerative diseases and a putative mechanism of action for pharmacological interventions. [11C]-UCBJ positron emission tomography (PET), which quantifies synaptic vesicle glycoprotein 2A (SV2A) density, offers the most direct in vivo measure of human...
Abstract Background Recent clinical and neuroscientific work has revived interest in psychedelic-assisted therapies as promising treatments for a range of psychiatric conditions. Mechanistically, classical psychedelics and atypical agents such as ketamine appear to act as catalysts of neural and psychological flexibility, disrupting entrenched patterns of activity in “stuck” brain networks and...
Abstract Background Clinical studies have shown that ketamine and classic psychedelics can produce robust and rapid antidepressant effects after a single or a few administrations. However, the neurobiological mechanisms driving these long-lasting changes remain unclear. A leading framework proposes that both drug classes induce sustained increases in neuroplasticity, potentially reshaping...
Background Anorexia nervosa is a debilitating eating disorder with high mortality and chronicity rates owing to the paucity of effective existing treatments. Several clinical trials using psilocybin therapy have demonstrated therapeutic efficacy and safety in psychiatric conditions, including anorexia nervosa. Aims This study aimed to further assess the safety, feasibility and potential...
Setting up a psychedelic study can be a long, arduous, and Kafkaesque process. Researchers are faced with a host of challenges in this rapidly evolving field, necessitating a range of considerations that remain largely unstandardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the...
Abstract A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and...
Abstract Rationale: Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, women remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. Objectives This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex...
Abstract In recent decades, the psychedelic psilocybin has been studied as a potential treatment for major depressive disorder (MDD), offering an alternative to traditional antidepressants. However, the brain changes underlying the clinical effects of different interventions remain unclear. Here, we investigated the effects of psilocybin and a conventional antidepressant, escitalopram, from the...
Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain...
We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and...
Major depressive disorder (MDD) is a leading cause of disability worldwide, yet many patients have inadequate responses to current treatments. Dimethyltryptamine (DMT), a serotonergic psychedelic with rapid onset and short duration, shows promise as a potential antidepressant (AD), although clinical evidence in MDD remains limited. We conducted a phase IIa, double-blind, placebo-controlled,...
Psychedelic compound N,N-Dimethyltryptamine (DMT) is renowned for inducing highly immersive experiences, often including encounters with seemingly sentient presences. While such phenomena are well documented, immersion under psychedelics remains conceptually underdefined and phenomenologically underexplored. Here we apply micro-phenomenology to characterize immersion under DMT as a structured...
Background:Adverse childhood experiences (ACEs) are known to contribute to mental health issues and interfere with response to mental health interventions. Psychedelics have been found to improve mental health outcomes; however, the exploration of the effects of psychedelics on mental health in those with higher ACEs remains limited. The present study aimed to examine mental health outcomes and...
Abstract Recent clinical trial data suggests that ratings on depression scales are lowered after psilocybin therapy compared to placebo, though it is unclear what neuropsychological mechanisms underpin these effects. This study compared psilocybin, with an established antidepressant, escitalopram, to investigate whether there are shared or distinct effects on emotional information processing....
Lysergic acid diethylamide (LSD) and 3,4-Methylenedioxymethamphetamine (MDMA) are widely used psychoactive drugs and their potential use in psychiatric medicine is currently generating interest. The mechanism by which these drugs may assist recovery in various disorders such as addiction and post-traumatic stress disorder (PTSD) is still not well understood. Most investigations of the effects...
It is 60 years since ketamine was first tested in humans as an alternative but safer anaesthetic to PCP (phencyclidine) (Corssen and Domino 1966). It became widely used as the “buddy drug” for combatants in the Vietnam War: because of its great safety margin, it could be injected into wounded personnel by their buddies to relieve pain before the arrival of the medical team. Because of...
Meditation and psychedelics have separately been studied as powerful tools for probing consciousness through their capacity to deconstruct the sense of self. Yet, direct empirical comparisons remain scarce, particularly in expert meditators. Here, we report for the first time a case study in which an advanced meditator and Lama from the Mahāmudrā meditation tradition engaged in a traditional...
Psychedelics are undergoing a clinical research renaissance, with compounds such as psilocybin advancing to Phase 3 trials for treatment-resistant depression and receiving fast-track or breakthrough designations from regulatory agencies. Despite this progress, the field lacks standardized terminology to guide clinical development, dosing, safety monitoring, and regulatory classification. Here,...
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Abstract Background: Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional...
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 chronic neurological and psychological...
Abstract Determining the scale of neural representations is a central challenge in neuroscience. While localized representations have traditionally dominated, evidence suggests information is also encoded in distributed, hierarchical networks. Recent research indicates that the hierarchy of causal influences shaping functional patterns serves as a signature of distinct brain states, with...
Obsessive-compulsive disorder (OCD) is a common and disabling condition. A large proportion of patients fail to respond to first-line treatment with serotonin reuptake inhibitors either selective serotonin reuptake inhibitors (SSRIs) or clomipramine. Preliminary evidence suggests psilocybin, a serotonin receptor agonist, might be efficacious. We conducted a pharmacological challenge study to...
The following part of the abstract had a minor error: ‘Following PT, there was greater activation in the ventromedial prefrontal cortex and sensory regions, and reduced activation in the angular gyrus.’ This is now corrected to ‘Following PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions.’ The original article...