OPEN Foundation

Day: 4 November 2020

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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Prescribing meaning: hedonistic perspectives on the therapeutic use of psychedelic-assisted meaning enhancement

January 3, 2022 / Other disciplines, Other substances, Papers, Philosophy, Psychology, Psychotherapy / Leave a Comment / By

Abstract

The recent renaissance in research on psychedelic-assisted psychotherapy is showing great promise for the treatment of many psychiatric conditions. Interestingly, therapeutic outcomes for patients undergoing these treatments are predicted by the occurrence of a mystical experience-an experience characterised in part by a sense of profound meaning. This has led to hypotheses that psychedelic-assisted psychotherapy is therapeutic because it enhances perception of meaning, and consequently leads to a meaning response (a therapeutic mechanism that has been well described in the philosophical literature on the placebo effect). The putative mechanism of action of psychedelics as meaning enhancers raises normative ethical questions as to whether it can be justified to pharmacologically increase the perception of meaning in order to heal patients. Using the perspectives of hedonistic moral theories, this paper argues that if psychedelics operate as meaning enhancers, psychedelic-assisted psychotherapy can be ethically justified. An anti-hedonistic objection is presented by applying Robert Nozick’s Experience Machine thought experiment to the case of psychedelic-assisted psychotherapy. However, it is argued that this objection falls short for two reasons. First, even if pleasure and pain are not the only consequences which have moral value they are not morally irrelevant, therefore, therapeutic meaning enhancement can still be justified in cases of extreme suffering. Second, it is possible that psychedelic states of consciousness do not represent a false reality, hence their therapeutic meaning enhancement is not problematic according to Nozick’s standards.

Miceli McMillan R. (2021). Prescribing meaning: hedonistic perspectives on the therapeutic use of psychedelic-assisted meaning enhancement. Journal of medical ethics, 47(10), 701–705. https://doi.org/10.1136/medethics-2020-106619

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Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis

January 3, 2022 / Ayahuasca, LSD, Mushrooms / Psilocybin, Papers, Personality, Psychiatry, Psychology, Spirituality / Leave a Comment / By / , , , , , ,

Abstract

Background: Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias.

Methods: We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain.

Results: A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges’ gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects.

Conclusions: High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

Goldberg, S. B., Shechet, B., Nicholas, C. R., Ng, C. W., Deole, G., Chen, Z., & Raison, C. L. (2020). Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis. Psychological medicine, 50(16), 2655–2666. https://doi.org/10.1017/S003329172000389X

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Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin

January 3, 2022 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychopharmacology / Leave a Comment / By / , , ,

Abstract

Background: Psilocybin is a serotonergic psychedelic found in “magic mushrooms” with a putative therapeutic potential for treatment-resistant depression, anxiety, obsessive-compulsive disorder, and addiction. In rodents, psilocybin acutely induces plasticity-related immediate early genes in cortical tissue; however, studies into the effects on subcortical regions, of different doses, and the subsequent translation of corresponding proteins are lacking.

Methods: We examined the acute effects of a single administration of psilocybin (0.5-20 mg/kg) on the expression of selected genes in the prefrontal cortex and hippocampus. In total, 46 target genes and eight reference genes were assessed using real-time quantitative polymerase chain reaction. Corresponding protein levels of the three most commonly regulated genes were assessed using Western blotting.

Results: In the prefrontal cortex, psilocybin increased the expression of Cebpb, c-Fos, Dups1, Fosb, Junb, Iκβ-α, Nr4a1, P11, Psd95, and Sgk1, and decreased the expression of Clk1. In the hippocampus, psilocybin strongly increased the expression of Arrdc2, Dusp1, Iκβ-α, and Sgk1 in a dose-dependent manner, and decreased the expression of Arc, Clk1, Egr2, and Ptgs2. Protein levels of Sgk1, Dusp1, and Iκβ-α showed only partial agreement with transcriptional patterns, stressing the importance of assessing downstream translation when investigating rapid gene responses.

Conclusion: The present study demonstrates that psilocybin rapidly induces gene expression related to neuroplasticity, biased towards the prefrontal cortex, compared to the hippocampus. Our findings provide further evidence for the rapid plasticity-promoting effects of psilocybin.

Jefsen, O. H., Elfving, B., Wegener, G., & Müller, H. K. (2021). Transcriptional regulation in the rat prefrontal cortex and hippocampus after a single administration of psilocybin. Journal of psychopharmacology (Oxford, England), 35(4), 483–493. https://doi.org/10.1177/0269881120959614O.

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30 April - Q&A with Rick Strassman

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