The fungivore-deterrence hypothesis, that psilocybin evolved as a chemical defence against arthropod fungivores via 5-HT receptor agonism, has become the working consensus in fungal chemical ecology, despite resting on a phylogenomic pattern of horizontal gene transfer among saprotrophs and remarkably little direct experimental evidence. Recent biochemistry ...
Psilocybin, a psychedelic drug with reported anxiolytic and antidepressant potential, is rapidly metabolized to its active metabolite psilocin. However, a lack of adequate toxicity studies and tissue distribution studies currently restricts its development and application. This study combined behavioral assays in zebrafish with desorption electrospray ioniza...
Stable, high-level biosynthesis of complex natural products requires precise control of heterologous pathway expression, yet transcriptional architectures optimized on plasmids often fail when transferred to the chromosome. Here, we present ePathIntegrate, a genome-centric pathway engineering strategy that leverages CRISPR-associated transposases (CASTs) to ...
Psilocin is a psychedelic indole alkaloid and one of the major human metabolites of its phosphorylated precursor, psilocybin. Psilocin binds to the serotonin receptor, 5-HT2A, and dose-dependently induces hallucinogenic effects stronger than psilocybin. As a result, psilocin has been a drug of interest in the analytical toxicology community for years. In viv...
Apart from the psychedelic psilocybin, the metabolite spectrum of Psilocybe "magic mushrooms" comprises sesquiterpenes, a class of natural products known to exhibit receptor-modulating bioactivities. However, the composition of the sesquiterpene profile has largely remained an open question. Here, we report the characterization of five Psilocybe cubensis ses...
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), along with putative minor metabolites and several deuterium-labeled derivatives. Psilocybin, psilocin, psilocin-O-glucuronide, and 4-HIAA were assayed for engage...
PcncAAAD is a noncanonical fungal aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. Unlike its mammalian and plant counterparts, PcncAAAD is activated by calcium, although the exact activation mechanism remains unclear. Here, we establish an in silico RMSD-based evaluation model throu...
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...
The therapeutic potential of psilocybin in treating psychiatric disorders has gained attention recently. While most research has focused on isolated psilocybin, evidence suggests that whole mushroom extracts exhibit greater efficacy, implicating a possible entourage effect of additional bioactive compounds. This study aimed to elucidate the holistic neuropha...
BACKGROUND: The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmissi...
ABSTRACT Psilocybin, an indole alkaloid of psychedelic mushrooms, has the potential to sustainably improve the treatment of several psychiatric diseases. So far, the psilocybin demand for clinical trials has been met by chemical synthesis. In this study, we pursued the biotechnological approach to develop a psilocybin production process utilizing an overprod...
After many years of stigma and neglect, there is a resurgence of interest in the therapeutic use of psychedelic drugs. Anecdotal and evidence-based reports indicate psychedelics as a possible treatment for depression, anxiety, PTSD, substance abuse, and other disorders resistant to conventional medical interventions. The available data, however, are limited ...
method was developed for the analysis of serotonin in Caenorhabditis elegans. Samples were subjected to solvent-solvent extraction from basic conditions into n-heptanol. The serotonin was then back-extracted into acetic acid, the solution diluted into basic buffer, and labelled with 3-(2-furoyl) quinoline-2-carboxaldehyde in the presence of cyanide. The samp...
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 (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...
Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilo...
