Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition in which prenatal stress and long-lasting disruptions of excitatory-inhibitory (E/I) balance have been implicated as key vulnerability factors. Although established pharmacological and behavioral treatments are effective for many individuals, they are not universally ...
The goal of this study is to test addiction-related brain circuitry (motivation/reward and inhibition) as well as neurocognitive circuitry prior to and following low or high dose psilocybin (PEX010 from Filament). Using fMRI, we will examine brain circuits relevant to drug relapse as well as neurocognitive flexibility circuits in individuals with opioid use ...
This is an observational study which does NOT directly administer a psychedelic substance but rather recruits participants who are already participating in another clinical trial in which they may receive a serotonergic psychedelic. The goal of this observational study is to learn how the brain's information processing changes during and following administra...
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, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (MDD)[1, 2], yet the neural mechanisms underlying these effects remain unclear. Negative affective biases are an important neuropsychological mechanism central to the development and perpetuation of MDD[3]. Using a translat...
Background: Psilocybin is a psychoactive compound found in hallucinogenic mushrooms and is rapidly dephosphorylated in vivo to psilocin, its pharmacologically active metabolite. Despite the growing clinical and scientific interest in these substances, information regarding their interaction with cytochrome P450 (CYP450) enzymes remains scarce, raising concer...
We carried out a systematic review of modern-era (1990-2025) placebo-controlled studies assessing the acute and post-acute effects of lysergic acid diethylamide, dimethyltryptamine and psilocybin on cognitive and psychological functions. From February 28 to March 19, 2025, PubMed and APA PsychINFO were systematically searched for placebo-controlled studies e...
Psychedelics, particularly psilocybin, have shown therapeutic potential across several psychiatric conditions, including depression, anxiety, obsessive-compulsive disorder, and anorexia nervosa (AN). These disorders often share social deficits that may be effectively alleviated by psychedelics considering their use has been linked with emotional empathy and ...
Emerging evidence suggests that classical psychedelics may offer therapeutic potential for opioid use disorder (OUD) by alleviating key hallmarks such as altered reward processing and dependence. However, the mechanisms behind these effects remain unclear. Our data demonstrate that a single administration of the psychedelic psilocybin (PSI) reduces condition...
Investigators will recruit 36 individuals on MAT for OUD for a double-blind, placebo-controlled design to determine whether PEX010 (25-mg/d) shows preliminary efficacy on neural correlates of neurocognition and on clinical outcomes. Participants will be randomized to either (single dose) 25-mg (PEX010-25 group) or 1-mg (PPEX010-1 group) PEX010 in a 2:1 ratio...
This study seeks to provide insight on psilocybin's effects on mechanisms of chronic pain among patients with co-morbid chronic low back pain and depression (CLBP+D). Participants will receive either a single high-dose of psilocybin (25mg absolute dose) or methylphenidate (40mg absolute dose). Participants will be asked to complete assessments of pain, depre...
Abstract Classic serotonergic psychedelics engage 5-HT receptors throughout the nervous system, but how maternal exposure intersects with embryonic brain interfaces is poorly defined. Here we tested in mice whether maternally administered lysergic acid diethylamide (LSD) accesses embryonic cerebrospinal fluid (CSF) and whether embryonic choroid plexus (ChP) ...
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine, 1) is the main indolethyl-amine natural product of psychotropic (so-called "magic") mushrooms. The majority of 1-producing species belongs to the eponymous genus Psilocybe, for which the biosynthetic events, beginning from l-tryptophan (2), and the involved enzymes have thoroughly been characterized. Some I...
Decades of cross-species research highlight the claustrums extensive bidirectional connectivity with cortical and subcortical regions, implicating it in higher-order cognitive processes requiring synchronized brain states. Psychedelics may disrupt this synchrony by modulating claustro-cortical signaling, reflected by the dissolution of cortical network signa...
Background and HypothesisVisual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. T...
Background and Hypothesis Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. ...
Recent advancements in the study of psilocybin and its active metabolite psilocin have highlighted their unique psychedelic properties and potential therapeutic applications, particularly in the rapid and sustained treatment of depression. However, the potent acute psychedelic effects of psilocybin necessitate a deeper understanding of the neural mechanisms ...