The 5-HT2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and other serotonergic hallucinogens (psychedelic drugs). Although a large amount of experimental work has been conducted to characterize the pharmacology of psilocybin and its dephosphorylated metabolite psilocin (4-hydroxy-N,N-dimethyltryptamine)...
Psilocybin-containing mushrooms, commonly known as magic mushrooms, have been used since ancient and recent times for depression and to improve quality of life. However, their anti-inflammatory properties are not known. The study aims at investing cytotoxicity; antioxidant; and, for the first time, anti-inflammatory effects of Psilocybe natalensis, a psilocy...
Psychotropic Psilocybe mushrooms biosynthesize their principal natural product psilocybin in five steps, among them a phosphotransfer and two methyltransfer reactions, which consume one equivalent of 5'-adenosine triphosphate (ATP) and two equivalents of S-adenosyl-l-methionine (SAM). This short but co-substrate-intensive pathway requires nucleoside cofactor...
BackgroundMescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly understood.ObjectivesThis article aims to fully review pharmacokinetics and pharmacodynamics of mescaline, foc...
The fungal genus Psilocybe and other genera comprise numerous mushroom species that biosynthesize psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine). It represents the prodrug to its dephosphorylated psychotropic analogue, psilocin. The colloquial term "magic mushrooms" for these fungi alludes to their hallucinogenic effects and to their use as recreational...
Psilocybe mushrooms are best known for their l-tryptophan-derived psychotropic alkaloid psilocybin. Dimethylation of norbaeocystin, the precursor of psilocybin, by the enzyme PsiM is a critical step during the biosynthesis of psilocybin. However, the "magic" mushroom Psilocybe serbica also mono- and dimethylates l-tryptophan, which is incompatible with the s...
Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the main alkaloid of the fungal genus Psilocybe, the so-called "magic mushrooms." The pharmaceutical interest in this psychotropic natural product as a future medication to treat depression and anxiety is strongly re-emerging. Here, we present an enhanced enzymatic route of psilocybin production by addin...
Bufotenine is an alkaloid derived from serotonin, structurally similar to LSD and psilocin. This molecule is able to inhibit the rabies virus infection in in vitro and in vivo models, increasing the survival rate of infected animals. Being a very promising molecule for an incurable disease and because of the fact that there is no consensus regarding its neur...
This chapter reviews what is known about the therapeutic uses of the serotonergic or classic hallucinogens, i.e., psychoactive drugs such as LSD and psilocybin that exert their effects primarily through agonist activity at serotonin 2A (5HT2A) receptors. Following a review of the history of human use and scientific study of these drugs, the data from clinica...
Five Psilocybe species with unresolved systematic position (P. atrobrunnea, P. laetissima, P. medullosa, P. pelliculosa, and P. silvatica) were investigated using four molecular markers (EF1-α, ITS, LSU, and IGS). Phylogenetic analysis revealed that with the exception of P. laetissima, which is now rightfully classified in the genus Leratiomyces, all investi...
The serotonin 5-HT(2A) receptor is a primary target of psychedelic hallucinogens such as lysergic acid diethylamine, mescaline, and psilocybin, which reproduce some of the core symptoms of schizophrenia. An incompletely resolved paradox is that only some 5-HT(2A) receptor agonists exhibit hallucinogenic activity, whereas structurally related agonists with co...
Human UDP-glucuronosyltransferases (UGTs) are important in the metabolic elimination of xenobiotics and endogenous compounds from the body. These enzymes transfer glucuronic acid moiety from the cosubstrate, UDP-glucuronic acid (UDPGA), to nucleophilic groups of small organic molecules, such as hydroxyl, carboxylic, or amino group. The conjugation of these m...
Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, th...
Study objectiveThe Meixner test has been suggested to identify the presence of alpha-amanitin, one of the toxic compounds in Amanita mushrooms. We attempted to determine the detection limit of the Meixner test for alpha-amanitin and to determine the percentage of positive sample interpretation compared with other mushroom indole compounds.MethodsThis was a 2...
The action of P. cubensis mushroom extract, containing psilocybin (PCB) and psilocin, on spike activity of hippocampal CA1 pyramidal neurons was studied in in vitro rat brain slices. In 38 (76%) out of 50 investigated neurons spike activity was decreased, in 2 (4%) cells it increased. There was no response 10 (20%) neurons. Application of the extract caused ...
A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activa...
The neurotropic effect of Psilocybe cubensis (Earle) Sing, dried biomass and fruiting bodies containing the indole hallucinogens psilocybin and psilocine on spike activity of pyramidal neurons from the rat hippocampal CAl region slices has been studied. Extracellularly responses of 50 neurons were recorded, 34 during the application of biomass extract (BME) ...
The enantiomers of 3-(N-methylpyrrolidin-2-ylmethyl)-5-methoxyindole, 1, and 3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole, 3, were prepared using an asymmetric synthesis that employed (+)- or (-)-proline. A new approach was developed that had certain advantages over the synthesis originally reported for the isomers of 1. (+/-)-3-(N-Methylpyrrolidin-3-yl)...
Several specimens of Psilocybe and Copelandia species in Koh Samui, Thailand were recently collected for herbarium deposit and scientific study. This paper presents an ethnomycological and biochemical study of one of the species; P. samuiensis Guzmán, Bandala and Allen, a new psychoactive gill fungus reported from Thailand. Mycelium for the cultivation of P....
Psilocybin and psilocin at luminal concentrations of about 20 nmol/ml were incubated aerobically with everted sacs from rat jejunum and colon. When incubation was terminated, samples of the lumen and blood side solutions and of the intestinal tissue were analyzed for parent drug and metabolites by HPLC using a multidetector system. Both sacs caused hydrolysi...
