OPEN Foundation

M. Kuchar

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

November 30, 2021 / Chemistry, Mushrooms / Psilocybin, Papers / Leave a Comment / By / , , , , ,

Abstract

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.

Gotvaldová, K., Hájková, K., Borovička, J., Jurok, R., Cihlářová, P., & Kuchař, M. (2021). Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis. Drug testing and analysis, 13(2), 439–446. https://doi.org/10.1002/dta.2950

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Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting

October 25, 2018 / Consciousness, Creativity, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , , , , ,

Abstract

INTRODUCTION:

Taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults.

METHODS:

During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested.

RESULTS:

We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.

CONCLUSION:

While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.

Prochazkova, L., Lippelt, D. P., Colzato, L. S., Kuchar, M., Sjoerds, Z., & Hommel, B. (2018). Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting. Psychopharmacology, 235(12), 3401-3413., 10.1007/s00213-018-5049-7
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Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue—Behavioural, pharmacokinetic and metabolic studies in the Wistar rat

May 4, 2016 / Neuroscience, New substances, Other substances, Papers, Psychopharmacology, Publications, Safety, Toxicology / By / , , , , ,

Abstract

Methoxetamine (MXE) is a novel psychoactive compound (NPS) that emerged in 2010 as a substitute for the dissociative anaesthetic ketamine. MXE has a reputation of carrying a lower risk of harm than ketamine, however a number of deaths have been reported. Currently very little is known about the psychopharmacological effects of this compound or its toxicity; therefore we tested, in Wistar rats, the effects of MXE in a series of behavioural tasks, measured its pharmacokinetics and urinary metabolites.

Locomotor activity and its spatial characteristics (in the open field) and sensorimotor gating (prepulse inhibition; PPI) were evaluated after 5, 10 and 40 mg/kg subcutaneous (sc.) MXE. Pharmacokinetics and brain: serum ratios were evaluated after 10 mg/kg sc. MXE so that peak drug concentration data could be used to complement interpretation of maximal behavioural effects. Finally, quantification of metabolites in rat urine collected over 24 h was performed after single bolus of MXE 40 mg/kg sc.

5 and 10 mg/kg MXE induced significant locomotor stimulation, in addition it increased thigmotaxis and decreased time spent in the centre of the open field (indicative of anxiogenesis). By contrast, 40 mg/kg reduced locomotion and increased time spent in the centre of the arena, suggesting sedation/anaesthesia or stereotypy. The duration of effects was present for at least 60–90 min, although for 5 mg/kg, locomotion diminished after 60 min. MXE decreased baseline acoustic startle response (ASR) and disrupted PPI, irrespective of testing-onset. MXE (all doses) reduced habituation but only at 60 min. Maximal brain levels of MXE were observed 30 min after administration, remained high at 60 min and progressively declined to around zero after six hours. MXE accumulated in the brain; the brain: serum ratio was between 2.06 and 2.93 throughout the whole observation. The most abundant urinary metabolite was O-desmethylmethoxetamine followed by normethoxetamine.

To conclude, MXE acts behaviourally as a typical dissociative anaesthetic with stimulant and anxiogenic effects at lower doses, sedative/anaesthetic effects at higher doses, and as a disruptor of sensorimotor gating. Its duration of action exceeds that of ketamine which is consistent with reports from MXE users. The accumulation of the drug in brain tissue might reflect MXE’s stronger potency compared to ketamine and indicate increased toxicity.

Horsley, R. R., Lhotkova, E., Hajkova, K., Jurasek, B., Kuchar, M., & Palenicek, T. (2016). Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue—Behavioural, pharmacokinetic and metabolic studies in the Wistar rat. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.05.002
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30 April - Q&A with Rick Strassman

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