In vivo, psilocybin is rapidly dephosphorylated to psilocin which induces psychedelic effects by interacting with the 5-HT2A receptor. Psilocin primarily undergoes glucuronidation or conversion to 4-hydroxyindole-3-acetic acid (4-HIAA). Herein, we investigated psilocybin’s metabolic pathways in vitro and in vivo, conducting a thorough analysis of the enzymes...
Abstract Background The underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT 2A receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that...
Introduction The use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psychiatric disorders, though the underlying mechanisms supporting these effects remain unclear. Psilocybin is a Schedule I substance that is dephosphorylated in vivo to form an active metabolite, psilocin. Psilacetin,...
Psilocybe "magic mushrooms" are chemically well understood for their psychotropic tryptamines. However, the diversity of their other specialized metabolites, in particular terpenoids, has largely remained an open question. Yet, knowledge on the natural product background is critical to understand if other compounds modulate the psychotropic pharmacological e...
ABSTRACT Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine...
ABSTRACT Intracellular calcium (Ca 2+ ) is ubiquitous to cell signaling across all biology. While existing fluorescent sensors and reporters can detect activated cells with elevated Ca 2+ levels, these approaches require implants to deliver light to deep tissue, precluding their noninvasive use in freely-behaving animals. Here we engineered an enzyme-catalyz...
Intestinal inflammation and dysbiosis can lead to inflammatory bowel diseases (IBD) and systemic inflammation, affecting multiple organs. Developing novel anti-inflammatory therapeutics is crucial for preventing IBD progression. Serotonin receptor type 2A (5-HT2A) ligands, including psilocybin (Psi), 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), and ketanser...
Abstract Background Psilocybin-containing mushrooms induce antidepressant and momentary increase in blood pressure (BP) with potential risk to users with cardiovascular diseases. Irregularities in nitric oxide (NO) levels play a key role in endothelial dysfunctions leading to increases in BP. Mushrooms species show large variation in potency which may potent...
Traditional psychedelics are undergoing a transformation from recreational drugs, to promising pharmaceutical drug candidates with the potential to provide an alternative treatment option for individuals struggling with mental illness. Sustainable and economic production methods are thus needed to facilitate enhanced study of these drug candidates to support...
Clinical trials of pharmacological approaches targeting the core features of autism have failed. This is despite evidence from preclinical studies, genetics, post-mortem studies and correlational analyses linking peripheral and central markers of multiple candidate neurochemical systems to brain function in autism. Whilst this has in part been explained by t...
Lysergic acid Diethylamide (LSD), psilocybin, and psilocin are being intensively evaluated as potential therapeutics to treat depression, anxiety, substance use disorder, and a host of other psychiatric illnesses. Pre-clinical investigation of these compounds in rodent models forms a key component of their drug development process. In this review, we will su...
The genus Psilocybe of Basidiomycota includes more than two hundred species of mushroom-forming fungi, which are widely known for the production of the secondary metabolite psilocybin, a prodrug of its in vivo dephosphorylated active metabolite psilocin [1]. Psilocybin is being currently used in numerous clinical trials including the treatment of Major Depre...
4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are pres...
Abstract Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of h...
The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and i...
Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy br...
BackgroundBacillus subtilis is a probiotic strain that is widely used as a feed supplement for ruminants. In this study, one B. subtilis strain isolated from the ruminal fluid of Holstein dairy cows was used for an ex vivo study with ruminal tissue explants. The main goal was to assess the potential endosymbiotic links between B. subtilis and the ruminal epi...
Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting...
Lysergic acid diethylamide (LSD) is known to induce powerful psychoactive effects in humans, which cemented its status as an important tool for clinical research. A range of analogues and derivatives has been investigated over the years, including those classified as new psychoactive substances. This study presents the characterization of the novel lysergami...
The active hallucinogen of magic mushrooms, psilocin, is being repurposed to treat nicotine addiction and treatment-resistant depression. Psilocin belongs to the tryptamine class of psychedelic compounds which include the hormone serotonin. It is believed that psilocin exerts its effect by binding to the serotonin 5-HT2A receptor. However, recent in-vivo evi...
