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...
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a...
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...
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...
ABSTRACT Acyloxymethyl (ACOM) derivatives of tryptamines such as the psychedelic drug psilocin and the anti-migraine drug sumatriptan bear potential as prodrugs. Previous synthetic approaches suffer from insufficient chemoselectivity between the desired functionalization of the phenolic (psilocin) or sulfonamide (sumatriptan) groups versus other reactive gro...
Psilocybe "magic mushrooms" are best known for their indolethylamine psilocybin, yet they encode enzymes for a much more diverse arsenal of small and potentially bioactive molecules. Herein, four Psilocybe cubensis clade III sesquiterpene synthases, CubB-CubE, whose genes are differently expressed in fruiting bodies compared to vegetative mycelium are report...
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-producing fungi have garnered attention due to accumulating evidence regarding the therapeutic potential of their principal component psilocybin. This diverse group of fungi harbors a wealth of less-studied metabolites, however, thus far most research has addressed them as a cohesive group. By optimizing an approach for extraction and analysis, we...
As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as pote...
Background and Purpose Demand for new antidepressants has resulted in a re-evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin-containing “magic” mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacologic...
BACKGROUND: Although Basidiomycota produce pharmaceutically and ecologically relevant natural products, knowledge of how they coordinate their primary and secondary metabolism is virtually non-existent. Upon transition from vegetative mycelium to carpophore formation, mushrooms of the genus Psilocybe use L-tryptophan to supply the biosynthesis of the psyched...
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...
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...
Psychedelic microdosing is the practice of taking very low doses of psychedelic substances, typically over a longer period of time. The long-term safety of chronic microdosing is relatively uncharacterized, but valvular heart disease (VHD) has been proposed as a potential risk due to activation of the serotonin 5-HT2B receptor. However, this risk has not yet...
Abstract Psilocybin is the psychoactive substance contained in the psilocybe(hallucinogenic) mushroom, which has received considerable attention among the scientific community in recent years. Human studies have demonstrated that even a single-dose of psilocybin can improve debilitating physical and psychological symptoms with durable long-term effects. >136...
