Zusammenfassung Psilocybin (4-Phosphoryloxy- N, N -dimethyltryptamin, 1 ) ist der hauptsächliche Indolethylamin-Naturstoff der psychotropen sogenannten Zauberpilze. Die Mehrheit der 1 -produzierenden Arten gehört zu der namensgebenden Gattung Psilocybe, für die die biosynthetischen Ereignisse, ausgehend von l -Tryptophan ( 2 ), sowie die beteiligten Enzyme g...
Psilocybin, a serotonergic psychedelic, is gaining attention for its rapid and sustained therapeutic effects in depression and other hard-to-treat neuropsychiatric conditions, potentially through its capacity to enhance neuronal plasticity. While its neuroplastic and therapeutic effects are commonly attributed to serotonin 2A (5-HT2A) receptor activation, em...
Schizophrenia is a highly polygenic disease, and several genetic variants associated with the disease converge on altered synaptic homeostasis. In particular, the gene encoding complement component 4 (C4) showed the strongest association with schizophrenia, and this protein is involved in complement-dependent and microglia-mediated synaptic pruning. As a mat...
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 medial prefro...
Serotonergic psychedelics, including the recreationally used psilocybin and LSD, have become promising therapeutic agents for the treatment of treatment-resistant depression. While it is generally agreed that they exhibit their antidepressant effects by inducing rapid and sustained neuroplasticity, the molecular mechanisms responsible are widely debated. In ...
Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease...
In the 1950s-60s, serotonergic psychedelic drugs were studied as potential adjuvants to psychotherapy to treat addiction and alcoholism. However, starting in the 70s, preclinical and clinical studies on psychedelics stopped for decades because legislation controlled its recreational use, citing their hallucinogenic and psychotomimetic effects, as well as the...
Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impression...
The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT2A serotonin receptor (5-HT2AR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety,...
Psilocybin, the naturally occurring psychedelic compound produced by hallucinogenic mushrooms, has received attention due to considerable clinical evidence for its therapeutic potential to treat various psychiatric and neurodegenerative indications. However, the underlying molecular mechanisms remain enigmatic, and few studies have explored its systemic impa...
Major depressive disorder is a debilitating condition, with many patients unresponsive to conventional monoaminergic antidepressants. Rapid-acting antidepressants such as ketamine and psilocybin offer promising alternatives, relieving symptoms within hours. Ketamine, an NMDA receptor antagonist, and psilocybin, a serotonergic psychedelic primarily targeting ...
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...
Psilocybin is among the most extensively studied psychedelics, with previous research suggesting its potential therapeutic role in suicide prevention. However, the precise mechanisms through which psilocybin may aid in suicide prevention remain unclear. This study thus employed network pharmacology and molecular docking tools to explore the mechanisms by whi...
BackgroundRecent evidence suggests that psychedelics can induce rapid and long-lasting antidepressant effects. The generally acknowledged explanation for these traits is the phenomenon of neuroplasticity, although the exact underlying molecular mechanisms remain unclear.AimsThis study investigates the effects of psilocin, lysergic acid diethylamide (LSD) and...
Abstract PcncAAAD is a calcium-activatable noncanonical aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. In this study, we establish an in silico RMSD-based evaluation model through molecular dynamics simulations, validated by in vitro enzyme assays, to decipher the enzyme’s calcium ...
Psilocybin therapy (PT) is emerging as an effective intervention for Major Depressive Disorder (MDD), offering comparable efficacy to conventional treatments like selective serotonin reuptake inhibitors (SSRIs). Music, an emotionally evocative stimulus, provides a valuable tool to explore changes in hedonic and predictive processing mechanisms via expectancy...
OBJECTIVE: Psychedelics are able to trigger highly intense and profound alterations in self-consciousness, perception, affective, and cognitive processes. Indeed, recent studies show that ketamine and psilocybin could be used as fast-acting antidepressants. However, the molecular and neurochemical mechanisms of these psychedelics and their actions at the lev...
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 themselv...
The few reports on effects of psychedelic substances on cerebral metabolic rate (CMRglc) indicate increases (psilocybin; human FDG-PET) or decreases (LSD, rat autoradiography; 5-MeO-DMT rat autoradiography). There are no reports of effects of DMT and/or harmine on cerebral energy metabolism. The primary objective of this study is thus to assess acute cerebro...
Psilocybin, a psychedelic compound found in specific hallucinogenic mushrooms, is known to induce changes in visual perception and experience in humans. However, there is little knowledge of the molecular mechanisms through which psilocybin affects vision-associated regions in the brain, such as the visual cortex. The current study determined both psilocybin...
