Structural basis for psilocybin biosynthesis

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 22, 2025

Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to biosynthesis psilocybin can enhance its process. In this study, we elucidate crystal structures L-tryptophan-specific decarboxylase PsiD both apo tryptamine-bound states, 4-hydroxytryptamine kinase PsiK bound substrate, several forms methyltransferase PsiM either or substrate-bound derived from psychedelic mushroom. Structure-based evaluations reveal mechanisms self-cleavage self-inhibition PsiD, along with sequential catalytic steps final compound, Additionally, showcase antidepressant properties intermediates on female mice experiencing depression-like behaviors induced by sub-chronic variable stress. Our studies establish a structural basis future using these emphasize clinical norbaeocystin. Here, authors provide mechanistic insights into enzymes, encompassing PsiK, PsiM. are evaluated.

Language: Английский

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Pharmacokinetics of Psilocybin: A Systematic Review

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 411 - 411

Published: March 25, 2025

Background: Psilocybin has shown promise in therapeutic applications for mental disorders. Understanding the pharmacokinetics of psilocybin and its active metabolite psilocin is crucial optimizing clinical use minimizing adverse effects. Methods: This systematic review involved a comprehensive search across MEDLINE, APA PsycINFO, Embase databases, from inception to December 2024, identifying original studies that investigated psilocybin. Results: Fourteen met inclusion criteria: eight laboratory-based six studies. Laboratory used animal models or vitro systems, while included 112 healthy human participants. rapidly dephosphorylated psilocin, which absorbed with Tmax values ranging 1.8 4 h following oral administration. Cmax varied dose-dependently, 8.2 ± 2.8 ng/mL (plasma) 871 (urine). One study reported bioavailability at 52.7 20%. The volume distribution was extensive, 277 92 L 1016 L, suggesting significant tissue distribution. Psilocin metabolism primarily mediated by CYP2D6 CYP3A4, secondary contributions monoamine oxidase A. It undergoes further hepatic biotransformation into 4-hydroxyindole-3-acetic acid 4-hydroxytryptophol. Elimination half-life studies, 1.5 h. Conclusions: demonstrate variability based on dosage, route, species. CYP enzymes play critical role metabolism, highlighting potential drug–drug interactions. These findings underscore importance research elucidate psilocybin’s pharmacokinetic profile, assessed vivo psilocin.

Language: Английский

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Psilocybin Biosynthesis Enhancement through Gene Source Optimization

Metabolic Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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A scoping review of the effects of mushroom and fungus extracts in rodent models of depression and tests of antidepressant activity

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 3, 2024

One of the most important developments in psychopharmacology past decade has been emergence novel treatments for mood disorders, such as psilocybin treatment-resistant depression. Psilocybin is commonly found different species mushroom; however, literature on mushroom and fungus extracts with potential antidepressant activity extends well beyond just psilocybin-containing mushrooms, includes both psychedelic non-psychedelic species. In current review, we systematically review preclinical extracts, their effects animal models depression tests activity. The PICO structure, PRISMA checklist Cochrane Handbook systematic reviews intervention were used to guide search strategy. A scoping was conducted electronic databases PubMed, CINAHL, Embase Web Science. identified 50 relevant suitable published studies. These included 19 seven other fungi. Nearly all studies reported antidepressant-like treatment extracts. Treatments delivered orally, acute chronically administered predominantly male rodents. Multiple used, common being unpredictable chronic mild stress, while tail suspension test forced swim frequently standalone screens. Details each experiment are discussed detail, an evaluation provided strengths weaknesses these

Language: Английский

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Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications

Biotechnology Progress, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Abstract Tryptamines play diverse roles as neurotransmitters and psychoactive compounds found in various organisms. Psilocybin, a notable tryptamine, has garnered attention for its therapeutic potential treating mental health disorders like depression anxiety. Despite promising applications, current extraction methods psilocybin are labor‐intensive economically limiting. We suggest biocatalysis sustainable alternative, leveraging enzymes to synthesize other tryptamines efficiently. By elucidating biosynthesis pathways, researchers aim advance synthetic methodologies industrial applications. This review underscores the transformative of enhancing our understanding tryptamine facilitating production high‐purity research use.

Language: Английский

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