Production Options for Psilocybin: Making of the Magic

Abstract

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 drugs. However, clinical trials have recognized psilocybin as a valuable candidate to be developed into a medication against depression and anxiety. We here highlight its recently elucidated biosynthesis, the concurrently developed concept of enzymatic in vitro and heterologous in vivo production, along with previous synthetic routes. The prospect of psilocybin as a promising therapeutic may entail an increased demand, which can be met by biotechnological production. Therefore, we also briefly touch on psilocybin's therapeutic relevance and pharmacology.

The Therapeutic Potential of Psilocybin

“…Aeruginascin demonstrates a high affinity for the 5-HT 1A , 5-HT 2A , and 5-HT 2B serotonin receptors [ 216 ] in producing euphoria-based hallucinogenic effects and, likely modulate the pharmacological action of psilocybin and the psilocybin-experience [ 217 ]. Norpsilocin is also a potent 5-HT 2A receptor agonist and is even reported to be more potent and possibly more efficacious than psilocin [ 207 ], while other the tryptamine derivatives baeocystin and norbaeocystin may serve as prodrugs to the bioactive compounds norpsilocin and 4-hydroxytryptamine, respectively [ 207 ], Baeocystin is a direct precursor to psilocybin [ 218 ], although it is not hallucinogenic by itself [ 207 ].…”

Simultaneous Production of Psilocybin and a Cocktail of β‐Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms

“…[1] Indisputably,m ushrooms producing psilocybin (1, Scheme 1) rank among the most prominente ntheogens and were considered the "flesh of the gods" (teonanacatl) by the Aztecs. [1] Numerous species within the fungal genus Psilocybe and other genera biosynthesize 1 which represents the phos-phorylated prodrug to the psychotropic agent psilocin (2), [2] first described by Albert Hofmanna nd co-workers sixty years ago. [3] Subsequently,N -methylated l-tryptophan as well as indoleethylamines,i .e.,t he intermediates of 1 baeocystin, nor-Scheme1.Schematicoverviewo np sychoactiveprinciples of Psilocybe mushrooms( green) and ayahuasca (blue), their biosynthetic origin, and their inactivation in the human body by monoamine oxidase(MAO) A. baeocystin, and norpsilocin were discovered.…”

Interpol review of controlled substances 2016–2019

“…Mushrooms (including Psilocybe mushrooms): 2016 MC-ICPMS method for precise V-51/V-50 isotope ratio measurements as a useful tool for identifying the origin of Amanita muscaria - a widespread toxic and hallucinogenic mushroom [ 783 ]; identification of mushroom samples from nine clinically reported cases in Thailand during a 7-year period based on nuclear ITS sequence data and identification of lethal peptide toxins using a reversed phase LC-MS method [ 784 ]; DNA-based taxonomic identification of basidiospores in hallucinogenic mushrooms cultivated in “grow-kits” seized by the police: LC-UV quali-quantitative determination of psilocybin and psilocin [ 785 ]; 2017 i dentification and quantitation of Psilocybe cubensis DNA using a quantitative qPCR-HRM assay [ 786 ]; review [ 787 ]; characterization of four psilocybin biosynthesis enzymes [ 788 ]; 1D and 2D NMR spectroscopy and high-resolution mass spectrometry for the identification of norpsilocin in Psilocybe cubensis [ 789 ]; isolation of 10 compounds from Psilocybe merdaria and structural determination from the analysis of 1D and 2D NMR and MS data [ 790 ]; characterization of four psilocybin biosynthesis enzymes [ 788 ]; 2018 Detection and identification of psilocybe cubensis DNA using a real-time PCR assay [ 791 ]; an enhanced enzymatic route of psilocybin production by adding the tryptophan synthase of the mushroom Psilocybe cubensis (TrpB) to the reaction [ 792 ]; review [ 793 ]; 2019 review [ 794 ]; morphological, chemical, and genetic analysis of mycelia of psychedelic fungi collected from a clandestine laboratory using SEM, MS, HRM and ITS sequencing [ 795 ];…”