Psychedelic drugs are poised to become mainstream treatments, yet we lack a circuit-level account of how they reshape brain activity. Emerging evidence suggests that multiple psychedelic compounds modulate activity in the brain's default mode network (DMN), often interpreted as either increased or decreased bottom-up hierarchical processing. Most imaging stu...
ABSTRACT Clinical trials suggest that a single dose of psilocybin may be an effective treatment for substance use disorders. Choice impulsivity is a value-based decision-making bias that predicts drug-intake escalation and is commonly associated with substance use disorders. The dorsomedial prefrontal cortex regulates choice impulsivity and is enriched with ...
Mescaline, a 5-HT2A agonist psychedelic used ceremonially for millennia, lacks neuroimaging characterization due to its Schedule 1 status. Using pharmacological and resting-state fMRI in awake rats, we report mescaline's first comprehensive neurobiological profile. Acutely, mescaline produced cerebellar-selective BOLD suppression, suggesting functional disco...
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research gro...
Uncovering the neural basis of psychedelics’ potent effects on brain activity and conscious experience has great potential for understanding their therapeutic effects. Numerous studies using functional magnetic resonance imaging (fMRI) uncovered a strong effect of psychedelics on global properties of fMRI signal, but how they map to underlying neural phenome...
Psilocin, a naturally occurring hallucinogenic component of magic mushrooms, exerts notable psychoactive effects in both humans and rodents. However, the underlying mechanisms remain not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a valuable tool in many preclinical and clinical trials for invest...
INTRODUCTION: Sertonergic psychedelics LSD, psilocin and DMT, have been shown to hold a great potential for treatment of various neuropsychiatric conditions, such as major depressive disorder, addiction, and end-of-life anxiety. Effects of these substances on neuronal activity and plasticity have been demonstrated, however, better understanding of their mech...
BACKGROUND: Psilocybin has shown rapid and sustained antidepressant effects in patients with major depressive disorder, yet the neurobiological mechanisms underlying these outcomes remain unclear. AIMS: receptor occupancy (RO) achieved after administration of psilocybin and its effects on behavior and markers of neuroplasticity in mice. METHODS: H]MDL-100,90...
Abstract Recent clinical breakthroughs hold great promise for the application of psilocybin in the treatments of psychological disorders, such as depression, addiction, and obsessive-compulsive disorder. Psilocybin is a psychedelic whose metabolite, psilocin, is a 5-HT2A receptor agonist. Nevertheless, the underlying mechanisms for the effects of psilocybin ...
Alcohol use disorder (AUD) is a highly prevalent disorder with limited therapeutic options. The central amygdala (CeA) is a critical brain region as dysregulation within the CeA and the corticotropin-releasing factor (CRF) system are associated with AUD pathology. CeA CRF1 receptors regulate alcohol drinking and have served as a therapeutic target in alcohol...
Abstract High-grade gliomas are the most aggressive form of brain tumors, and neuronal activity has emerged as a driver of glioma pathophysiology. Activity-dependent glioma growth results from paracrine factor signaling and bona fide neuron-to-glioma synapses that integrate glioma cells into brain-wide neuronal circuits. Here, we report how glioma cells inte...
Psilocybin, and its active metabolite psilocin, have seen renewed interest due to studies suggesting potential therapeutic utility. 5-Hydroxytryptamine2A receptors (5-HT2ARs) are primary mediators of the psychoactive effects of psychedelics in animals and humans, but the underlying neurobiological mechanisms remain poorly understood. Functional magnetic reso...
Many neuropsychiatric conditions, including depression, involve synaptic loss and atrophy of the prefrontal cortex. The rapid regrowth of cortical neurons has been hypothesized to explain the rapid and enduring therapeutic effects of psychedelics and the dissociative anesthetic ketamine. However, safety concerns related to hallucinogenic/dissociative propert...
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 ...
