Despite enormous interest in psychedelics for psychiatric interventions, potential underlying biological mechanisms remain unclear. Here, we confirm that a single dose of psilocybin increases synaptic transmission in mouse medial prefrontal cortex. Using scRNA-sequencing, we identify cell-type specific mechanisms of sustained neuroplastic effects. We show th...
ABSTRACT Psychedelics have reemerged as potential treatments for mental health disorders, yet their impact on stress-related brain regions remains poorly understood. Here, we provide the first real-time, in vivo evidence of psilocybin-induced neuronal activation, specifically in hypothalamic corticotropin-releasing hormone neurons. Notably, psilocybin elicit...
Over a decade after the first edition of "Behavioral Neurobiology of Alcohol Addiction," this chapter revisits the field at a critical juncture, marked by both persistent challenges and emerging opportunities. We reflect on the translational gap that has stalled the development of new treatments for alcohol use disorder (AUD), despite decades of promising pr...
SUMMARY We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the media...
The full therapeutic potential of serotonergic psychedelics (SP) in treating neuropsychiatric disorders, such as depression and schizophrenia, is limited by possible adverse effects, including perceptual disturbances and psychosis, which require administration in controlled clinical environments. This study investigates the synergistic benefits of combining ...
Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses 1-4. At the cellular level, psychedelics induce structural neural plasticity 5,6, exemplified by the drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells 7-9. A key question is how these cellular modifications map onto cell type-spec...
Psilocybin is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side ...
Recent studies highlight the promising use of psychedelic therapies for psychiatric disorders, including depression. The persisting clinical effects of psychedelics such as psilocybin are commonly attributed to activation of the serotonin 2A receptor (5-HT2AR) based on its role in the acute hallucinatory effects. However, the active metabolite of psilocybin ...
The distinct subjective effects that define psychedelics such as LSD, psilocybin or DOI as drug class are causally linked to activation of the serotonin 2A receptor (5-HT2A R). However, some aspects of 5-HT2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from non-psychedelic 5-HT2A R agonists. We developed an ex vivo...
BACKGROUND: Psilocybin is a psychedelic 5HT2A receptor agonist found in "magic mushrooms". Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to det...
Abstract Psychedelic drugs have profound effects on perception, cognition and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadm...
Psilocybin, a psychoactive substance derived from fungi, has been utilized historically by diverse cultures for both medicinal and non-medicinal purposes, owing to its ability to elicit profound sensory and cognitive alterations and sustain long-term changes in mood and cognition. Promising results from recent clinical studies have generated a wave of intere...
Antidepressants including selective serotonin reuptake inhibitors, ketamine, and psilocybin are all effective for treating depression despite their distinct primary mechanisms. We hypothesized that these drugs may share a common mechanism that underlies their therapeutic actions. We treated mice with one of the following: escitalopram, R- / S -/ RS- ketamine...
Background SAPAP3-knockout (KO) mice develop excessive self-grooming behavior at 4-6 months of age, serving as a model for obsessive-compulsive disorder (OCD). Given that anxiety often precedes OCD diagnosis in humans, this study investigated whether juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the self-grooming phenotype, and whe...
Abstract Chronic pain states are challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin can produce a sustained anti-nociceptive effect in a mouse model of chronic neuropathic pain. Beyond this, the single dose of psilocybin caused a dramatic increase in the anti-nociceptive potential of gabapentin, a widely...
Background: Recent evidence suggests that psychedelics are able to induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although exact underlying molecular mechanisms remain unclear. Aims: This study investigates selected neuroplastic effects of psilocin, lysergic ...
Serotonergic psychedelics (e.g., psilocybin, LSD) have potential to treat psychiatric disorders, with therapeutic effects lasting days to weeks after a single dose. Prominent theories suggest that psychedelics have a lasting effect on hierarchical brain circuits, reducing top-down influence on information processing to facilitate an unbiased, bottom-up reass...
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