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 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...
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...
Psychedelic compounds can induce rapid-acting and long-lasting antidepressant benefits. Understanding the role of their hallucinatory effects is crucial for shaping the future trajectory of antidepressant drug development. Photoswitchable compounds targeting the 5-HT2AR offer precise spatio-temporal control over the activation of different downstream pathways. In this work, we computationally...
Ketamine, a dissociative compound, shows promise in treating mood disorders, including treatment-resistant depression (TRD) and bipolar disorder (BD). Despite its therapeutic potential, the neurophysiological mechanisms underlying ketamine's effects are not fully understood. This study explored acute neurophysiological changes induced by subanesthetic doses of ketamine in BD patients with...
Depressive disorders continue to pose a major clinical challenge worldwide, particularly given the high prevalence and increasing number of treatment-resistant cases. Over the past decade, advances in research have elucidated the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists in patients with major depressive disorder (MDD) and treatment-resistant depression (TRD)....
Neuroplasticity, the ability of the nervous system to adapt throughout an organism's lifespan, offers potential as both a biomarker and treatment target for neuropsychiatric conditions. Psychedelics, a burgeoning category of drugs, are increasingly prominent in psychiatric research, prompting inquiries into their mechanisms of action. Distinguishing themselves from traditional medications,...
High Resolution Image Download MS PowerPoint Slide Renewed scientific interest in psychedelic compounds represents one of the most promising avenues for addressing the current burden of mental health disorders. Classic psychedelics are a group of compounds that exhibit structural similarities to the naturally occurring neurotransmitter serotonin (5-HT). Acting on the 5-HT type 2A receptors (HT...
Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction. In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the...
Classic psychedelics are compounds that target the 5-hydroxytryptamine receptor type 2A (5-HT2AR), inducing profound changes in consciousness. Although these compounds most closely resemble the natural neurotransmitter serotonin, their therapeutic and psychoactive action is still not well understood. Therefore, a quantitative atomistic description of their interaction in the 5-HT2AR receptor is...
Due to their potential impact on mood and wellbeing there has been increasing interest in the potential of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) in the treatment of major depressive disorder (MDD). The aim of Part A of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) profile of escalating doses of SPL026 (DMT fumarate)...
Renewed scientific interest in psychedelic compounds represents one of the most promising avenues for addressing the current burden of mental health disorders. Classic psychedelics are a group of compounds that exhibit structural similarities to the naturally occurring neurotransmitter serotonin (5-HT). Acting on the 5-HT type 2A receptors (5-HT2AR), psychedelics induce enduring...