The study hypothesis is that the antidepressant effect of psilocybin is mediated by a normalization of the functioning of the positive valence system. Depressive states, especially moderate to severe depressions that associate a certain level of anhedonia, produce an overvaluation of the cost of efforts and an infra-evaluation of the possible rewards derived...
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...
Psilocybin has profound therapeutic potential for various mental health disorders, but its mechanisms of action are unknown. Functional MRI studies have reported the effects of psilocybin on brain activity and connectivity; however, these measurements rely on neurovascular coupling to infer neural activity changes and assume that blood flow responses to neur...
Both meditation and psychedelics are widely studied for their therapeutic potential in mental health. Recent research suggests potential synergies between mindfulness practice and psychedelics, though empirical studies have primarily focused on psilocybin. This study investigates the distinct and combined effects of mindfulness practice and an ayahuasca-insp...
In previous clinical trial work, the investigators observed lasting reductions in headache burden after limited dosing of psilocybin. This purpose of this study is to examine potential sources for this observed effect. This study will measure brain resting state functional connectivity (fMRI), central synaptic density (SV2A PET), peripheral markers of inflam...
The influence of ovarian hormone fluctuations on neurochemistry, cognition, and psychological responses remains insufficiently examined in current psychedelic research and clinical protocols. Traditional practices and case studies underscore the importance of accounting for these factors in investigations of psychedelic effects. This opinion paper explores t...
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...
In this study, we provide the first study to integrate molecular and functional neuroimaging during psychedelic drug effects in humans. Using simultaneous PET-MRI technology, we describe multiple brain actions of lysergic acid diethylamide (LSD) in healthy volunteers. We quantify the occupancy of LSD at cerebral serotonin 2A receptors and show that LSD incre...
This is an open-label, single-arm, pilot study exploring the neural, sensory, and cognitive effects of a single, medium dose of psilocybin in patients with chronic pain who already have implanted sensing-capable deep brain stimulation (DBS) devices. Outcomes include multi-site neural recording from previously placed ambulatory sensing-capable DBS devices, qu...
Human neuroimaging with functional Magnetic Resonance Imaging has been a key feature of the current wave of psychedelic research, in both healthy and clinical populations. The available data has suggested that classic psychedelics (psilocybin, LSD, DMT) have a characteristic effect of acutely and profoundly disrupting the normal pattern of resting-state conn...
Psilocybin is a psychedelic serotonergic compound that is renowned for its potent psychoactive effects. Over the past 15 years, an increasing number of controlled clinical trials showed that it has a fast-acting and sustainable efficacy in treating various psychiatric disorders. Neuroimaging studies have been conducted with the objective of elucidating the n...
This study will examine the synaptotrophic effects of psilocybin among medically healthy, detoxified OUD subjects. Eligible OUD participants will undergo pre- and post- psilocybin administration PET scans with the \[11C\]-UCB-J radiotracer while inpatient. Participants will undergo screening as outpatients at the Clinical Neuroscience Research Unit (CNRU). O...
This chapter reviews the effects of classic psychedelics on human oscillatory brain activity, as measured by resting-state electroencephalography (EEG) and magnetoencephalography (MEG). Across moderate to high doses of LSD, psilocybin, ayahuasca, and DMT, a consistent reduction in alpha power (8-13 Hz) emerges, particularly in occipital regions. Below 30 Hz,...
Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in cortical networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on cortex-wide network dynamics. Previous electroencephalographic studies of psychedelics in r...
Psychedelics can profoundly alter consciousness by reorganising brain connectivity; however, their effects are context-sensitive. To understand how this reorganisation depends on context, we collected and comprehensively analysed the largest psychedelic neuroimaging dataset to date. Sixty-two adults were scanned with functional MRI and EEG during rest and na...
Major Depressive Disorder (MDD) is typically characterized by altered linear functional connectivity (FC) across large-scale brain networks. Yet, it is unclear whether similar alterations are observed when nonlinear FC is examined. This study investigated how antidepressant treatment (i.e., psilocybin and escitalopram) modulates both linear FC and nonlinear ...
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/k...
Repetitive mild head injuries incurred while playing organized sports, during car accidents and falls, or in active military service are a major health problem. These head injuries induce cognitive, motor, and behavioral deficits that can last for months and even years with an increased risk of dementia, Parkinson’s disease, and chronic traumatic encephalopa...
ABSTRACT BACKGROUND AND PURPOSE: There is surging interest in the therapeutic potential of psychedelic compounds like psilocybin in the treatment of psychiatric illnesses like major depressive disorder (MDD). Recent studies point to the rapid antidepressant effect of psilocybin; however, the biological mechanisms underlying these differences remain unknown. ...
