Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis.

Psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin are tryptamines structurally similar to the neurotransmitter serotonin. Psilocybin and its pharmacologically active metabolite psilocin in particular are known for their psychoactive effects. These substances typically occur in most species of the genus Psilocybe (Fungi, Strophariaceae). Even the sclerotia of some of these fungi known as "magic truffles" are of growing interest in microdosing due to them improving cognitive function studies. In addition to microdosing studies, psilocybin has also been applied in clinical studies, but only its pure form has been administrated so far. Moreover, the determination of tryptamine alkaloids is used in forensic analysis. In this study, freshly cultivated fruit bodies of Psilocybe cubensis were used for monitoring stability (including storage and processing conditions of fruiting bodies). Furthermore, mycelium and the individual parts of the fruiting bodies (caps, stipes, and basidiospores) were also examined. The concentration of tryptamines in final extracts was analyzed using ultra-high-performance liquid chromatography coupled with mass spectrometry. No tryptamines were detected in the basidiospores, and only psilocin was present at 0.47 wt.% in the mycelium. The stipes contained approximately half the amount of tryptamine alkaloids (0.52 wt.%) than the caps (1.03 wt.%); however, these results were not statistically significant, as the concentration of tryptamines in individual fruiting bodies is highly variable. The storage conditions showed that the highest degradation of tryptamines was seen in fresh mushrooms stored at -80°C, and the lowest decay was seen in dried biomass stored in the dark at room temperature.

Systematic Error for Extraction of Controlled Substances from Plant/Fungal Materials.

The aim of this work was to investigate the applicability of a mathematical model developed for the description of supercritical fluid extraction (SFE) of cannabinoids from marijuana and hashish for liquid extraction of other substances. The mentioned model is applicable for dynamic SFE whose implementation is analogous to liquid-solid extraction in quasi-counter current mode. According to this model, quasi-counter current liquid-solid extractions were designed by calculation of component transport constants for extractions of psilocin from hallucinogenic mushroom, mescaline from hallucinogenic cactus, harmine from tropical lyan and salvinorin A from hallucinogenic sage. The mentioned model was found to be suitable for the determination of extraction time needed to reach a predefined extraction recovery for quasi-counter current liquid-solid extractions, as well, which allows the elimination of systematic error caused by the non-extracted part. The calculated component transport constants predict the expectable velocity of the extraction, i.e., the higher the component transport constant is, the higher the extraction velocity is. For mushrooms, it could be stated that preliminary treatment of mushrooms with liquid nitrogen significantly increases the extractability of psilocin.

Modulatory effects of ayahuasca on personality structure in a traditional framework.

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth. RATIONALE: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration. OBJECTIVES: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists. METHOD: Within a mixed design, we examined the effect of ayahuasca on participants' personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca). RESULTS: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism. CONCLUSIONS: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.

Psilocybin: from ancient magic to modern medicine.

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is an indole-based secondary metabolite produced by numerous species of mushrooms. South American Aztec Indians referred to them as teonanacatl, meaning "god's flesh," and they were used in religious and healing rituals. Spanish missionaries in the 1500s attempted to destroy all records and evidence of the use of these mushrooms. Nevertheless, a 16th century Spanish Franciscan friar and historian mentioned teonanacatl in his extensive writings, intriguing 20th century ethnopharmacologists and leading to a decades-long search for the identity of teonanacatl. Their search ultimately led to a 1957 photo-essay in a popular magazine, describing for the Western world the use of these mushrooms. Specimens were ultimately obtained, and their active principle identified and chemically synthesized. In the past 10-15 years several FDA-approved clinical studies have indicated potential medical value for psilocybin-assisted psychotherapy in treating depression, anxiety, and certain addictions. At present, assuming that the early clinical studies can be validated by larger studies, psilocybin is poised to make a significant impact on treatments available to psychiatric medicine.

Glucuronidation of psilocin and 4-hydroxyindole by the human UDP-glucuronosyltransferases.

We have examined the glucuronidation of psilocin, a hallucinogenic indole alkaloid, by the 19 recombinant human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A, and 2B. The glucuronidation of 4-hydroxyindole, a related indole that lacks the N,N-dimethylaminoethyl side chain, was studied as well. UGT1A10 exhibited the highest psilocin glucuronidation activity, whereas the activities of UGTs 1A9, 1A8, 1A7, and 1A6 were significantly lower. On the other hand, UGT1A6 was by far the most active enzyme mediating 4-hydroxyindole glucuronidation, whereas the activities of UGTs 1A7-1A10 toward 4-hydroxyindole resembled their respective psilocin glucuronidation rates. Psilocin glucuronidation by UGT1A10 followed Michaelis-Menten kinetics in which psilocin is a low-affinity high-turnover substrate (K(m) = 3.8 mM; V(max) = 2.5 nmol/min/mg). The kinetics of psilocin glucuronidation by UGT1A9 was more complex and may be best described by biphasic kinetics with both intermediate (K(m1) = 1.0 mM) and very low affinity components. The glucuronidation of 4-hydroxyindole by UGT1A6 exhibited higher affinity (K(m) = 178 microM) and strong substrate inhibition. Experiments with human liver and intestinal microsomes (HLM and HIM, respectively) revealed similar psilocin glucuronidation activity in both samples, but a much higher 4-hydroxyindole glucuronidation rate was found in HLM versus HIM. The expression levels of UGTs 1A6-1A10 in different tissues were studied by quantitative real-time-PCR, and the results, together with the activity assays findings, suggest that whereas psilocin may be subjected to extensive glucuronidation by UGT1A10 in the small intestine, UGT1A9 is likely the main contributor to its glucuronidation once it has been absorbed into the circulation.

Psilocybin mushroom (Psilocybe semilanceata) intoxication with myocardial infarction.

CASE REPORT: Intentional intoxication with natural hallucinogenic substances such as hallucinogenic mushrooms continues to be a major problem in the US and Europe, particularly in the harbor complex of northwest Poland (Pomerania). A case is described of Psilocybe intoxication in an 18-year-old man resulting in Wolff-Parkinson-White syndrome, arrhythmia, and myocardial infarction. The indole concentrations of hallucinogenic mushrooms may predict the risk for adverse central nervous system and cardiac toxicity.

Strategies for the capillary electrophoretic separation of indole alkaloids in Psilocybe semilanceata.

While the hallucinogenic mushrooms Psilocybe semilanceata have previously been analyzed for the indole alkaloids psilocybin and baeocystin by capillary zone electrophoresis (CZE) at pH 11.5, the present work focused on the development of an alternative and complementary capillary electrophoretic method for their identification. Owing to their structural similarity and zwitterionic nature, the compounds were difficult to resolve based on different interactions with cationic or anionic micelles. However, while the attempts with micellar electrokinetic chromatography (MEKC) were unsuccessful, rapid derivatization with propyl chloroformate and reanalysis by CZE at pH 11.5 was effective to support identification of the two indole alkaloids. Psilocin was difficult to analyze by CZE at pH 11.5 owing to comigration with the electroosmotic flow. For this compound, the pH of the running buffer was reduced to 7.2 to effectively enhance the electrophoretic mobility.

Extraction and analysis of indole derivatives from fungal biomass.

The occurrence and extraction of indole derivatives in six species from four genera of higher fungi were investigated. By using pure methanol for extraction of the mushrooms analysis revealed the highest concentrations of psilocybin and baeocystin. The psilocin content of the species was higher by using aqueous solutions of alcohols than with methanol alone but was an artificial phenomenon caused by enzymatic destruction of psilocybin. The extraction with dilute acetic acid yielded better results than with the water containing alcohols. The simple one-step procedure with methanol for the quantitative extraction is still the safest method to obtain the genuine alkaloids from fungal biomass.

Psychoactive mushroom use in Koh Samui and Koh Pha-Ngan, Thailand.

This paper presents the results of recent ethnomycological exploration in southern Thailand. Field observations, interviews and collection of fungi specimens were carried out primarily on two islands, Koh Samui and Koh Pha-ngan, situated in the western region of the Gulf of Siam. Some fieldwork was also conducted in the northern Thai province of Chiang Dao and in the southern Thai province of Surat Thani. During five separate excursions (1989-90), observations were made of occurrence, harvesting, use, and marketing of psychoactive fungi by local Thai natives (males and females, adults and children), foreign tourists, and German immigrants. The first records of psychoactive Psilocybe subcubensis and Copelandia dung fungi in Thailand are presented in this paper. These fungi exhibited intense bluing reactions when handled, indicating the presence of psilocybin and/or psilocin. Seven collections of Psilocybe cubensis (Earle) Singer and/or Psilocybe subcubensis Guzman and four collections of Copelandia sp. were harvested and sun-dried for herbarium deposit. These fungi are cultivated or occur spontaneously, often appearing in the decomposed manure of domesticated water buffalo (Bubalus bubalis) and at least three different species of cattle (Bos indicus, B. guarus, and B. sundaicus). The psychoactive fungi are cultivated in clandestine plots, both indoors and outdoors, in the uplands and villages on Koh Samui by both Thai natives and some foreigners. The sale of psychoactive fungi directly to tourists and to resort restaurants for use in edible food items such as omelettes and soups is discussed in detail. The preparation and sale of mushroom omelettes adulterated with artificial hallucinogens in some restaurants is also discussed. In addition, the marketing of items such as hand painted T-shirts, post cards, and posters bearing mushroom related motifs in Thailand is described.

An aqueous-organic extraction method for the isolation and identification of psilocin from hallucinogenic mushrooms.

A simple aqueous extraction method for the isolation and identification of psilocin from Psilocybe cubensis mushrooms is reported. This method employs a dephosphorylation of the phosphate ester to psilocin, which facilitates a greater product yield and simplifies identification. Psilocin extracted by this method is sufficiently concentrated and free of cocontaminants to allow identification by infrared spectroscopy and gas chromatography/mass spectrometry.

The occurrence of psilocybin in Gymnopilus species.

An accidental case of mushroom poisoning led to the detection of psilocybin in Gymnopilus validipes (Cortinariaceae). This compound was subsequently isolated (0.12% yield) by anion exchange and cellulose chromatography. Eighteen additional species of Gymnopilus were screened by a method capable of detecting 0.0004% psilocybin in dried carpophores. Psilocybin was detected in G. aeruginosus, G. luteus, G. viridans and G. spectabilis. The latter species has been previously reported to be hallucinogenic. This is the first report of psilocybin from this genus.

Baeocystin in psilocybe, conocybe and panaeolus.

Sixty collections of ten species referred to three families of the Agaricales have been analyzed for the presence of baeocystin by thin-layer chromatography. Baeocystin was detected in collections of Psilocybe, Conocybe, and Panaeolus from the U.S.A., Canada, Mexico, and Peru. Laboratory cultivated fruitbodies of Psilocybe cubensis, P. semilanceata, and P. cyanescens were also studied. Intra-species variation in the presence of decay rate of baeocystin, psilocybin and psilocin are discussed in terms of age and storage factors. In addition, evidence is presented to support the presence of 4-hydroxytryptamine in collections of P. baeocystis and P. cyanescens. The possible significance of baeocystin and 4-hydroxytryptamine in the biosynthesis of psilocybin in these organisms is discussed.