Psilocybin containing mushrooms: a rapidly developing biotechnology industry in the psychiatry, biomedical and nutraceutical fields

Abstract

Humans have collected and used hallucinogenic mushrooms for ethnic medicinal, recreational, and religious purposes since before recorded history. Currently, the use of these mushrooms is illegal in most countries, but where their use is legal they are applied as self medication. Psilocybin and psilocin, two psychoactive alkaloids, are naturally synthesized by hallucinogenic mushrooms. The chemical structure of these compounds are similar to the neurotransmitter serotonin. Activation of this system by psilocybin and psilocin may produce temporary changes in the brain that induce hallucinations and feelings of euphoria. Adjustment of the serotonin system in this way can moderate symptoms of related mental disorders. This review summarizes relevant and current information regarding the discovery of hallucinogenic mushrooms and their contained psychoactive compounds, the events that lead to their criminalization and decriminilization, and the state of knowledge of psilocybin, psilocin, and derivatives. Last, research on the psychoactive properties of these mushrooms is placed in perspective to possible applications for human dysfunctions.

Keywords: Hallucinogenic medicine; Hallucinogenic mushrooms; Psilocin; Psilocybin; Serotonergic Neurotransmitter System.

Fig. 1

Results from an advanced search builder in NCBI (National Centre for Biotechnology Information) using the terms “psilocybin” and “psilocin” or “psilocybin AND psilocin”, to investigate the amount of literature published (source NCBI dated 26/09/2021)

Fig. 2

Chemical structures of psilocybin and structurally related compounds. The illustrations was created by ChemDraw Ultra (https://chemistrydocs.com/chemdraw-ultra-12-0/)

Fig. 3

Multiple pathways for the biosynthesis of psilocybin in vivo. A The first biosynthesis pathway from tryptophan that is decarboxylated and methylated to N,N-dimethyltryptamine (DMT) (indicated with black arrows), that is oxidatively phosphorylated to psilocybin. B The second pathway from 4-hydroxytryptamine to 4-hydroxy-N-methyltryptamine to psilocin through methylation (indicated by dark grey arrows), and last psilocybin through phosphorylation (indicated by dark grey arrows). C The third biosynthesis pathway from tryptophan to norbaeocystin, and methylation of norbaeocystin and baeocystin resulting in psilocybin (indicated by light grey arrows). In the pathways the gene PsiD encodes for tryptophan decarboxylase, PsiH for a P₄₅₀ monooxygenase, PsiK for a kinase, and PsiM for a methyltransferase. The rectangle dotted box demarcated the three distinguishable pathways as indicated in the subsections of A, B and C. The illustrations were created by ChemDraw Ultra (https://chemistrydocs.com/chemdraw-ultra-12-0/)