Psilocybin

     

Molecular formula: C12H17N2O4P  

Molecular weight: 284.25g/mol  

 

Overview

 

Psilocybin is one of the of the most well-known, naturally occurring, psychedelic compounds. It is classified as an indole-alkylamine (tryptamine), with a similar molecular structure to LSD. It is found in its natural state within various types of fungi – most notably within the polyphyletic Psilocybe genus of hallucinogenic mushroom, some of which are noted below: 

 

  • Psilocybe Azurescens
  • Psilocybe Baeocystis
  • Psilocybe Bohemica
  • Psilocybe Semilanceata
  • Psilocybe Cubensis

 

 

History

 

There has been evidence to suggest that hallucinogenic mushrooms have been widely utilized as part of religious ceremonies within various, geographically separated, Mesoamerican ancient cultures – with the Aztecs referring to them as ‘teonanacatl’ (“flesh of god”). According to ‘The History of the Indies of New Spain’, published in c.1581 by Diego Duran, hallucinogenic mushrooms were consumed as part of festivities relating to the ascension to the throne of Aztec emperor ‘Moctezuma II’ in 1502. Further reports have described merchants consuming them as an inducer of revelatory visions. Following the defeat of the Aztecs to the Spanish empire, traditional religious practises such as the ritual use of hallucinogenic mushrooms were outlawed. In 1957, American ethnomycologist Gordon Wasson, physiologist Valentina Wasson and the French mycologist Roger Heim, completed an expedition in which they were able to identify several mushrooms producing psychedelic effects as belonging to the Psilocybe genus. Heim later cultured the mushrooms within a laboratory setting, sending culture samples to the well-known chemist Albert Hoffmann for analysis. Soon after, Hoffmann headed a research group with the aim of investigating the active compounds contained within the Psilocybe Mexicana mushroom. This lead to the successful identification and crystalline isolation of the active compound that would then become known as psilocybin.  

 

Pharmacology

 

Psilocybin undergoes rapid hepatic first pass metabolism in the body via dephosphorylation to produce four distinct metabolites:  

 

  • 4-hydroxy-N,N-dimethyltrypt-amine (psilocin)
  • 4-hydroxyindole-3-yl-acetaldehyde
  • 4-hydroxyindole-3-yl-acetic-acid
  • 4-hydroxytryptophol 

 

Early biochemical studies have determined that psilocin is the dominant pharmacologically active metabolite produced. This is supported by various ex vivo studies (utilizing rodent tissue), as well as various studies that have measured a similar qualitative/quantitative psychotropic effect in humans when equimolar amounts of psilocybin and psilocin were administered. Previous in vivo studies have shown psilocin to exert its clinical psychotropic effect via interactions with the serotonergic neurotransmission pathway, binding with various associated receptor subtypes in a fully agonistic or partially agonistic fashion. It has high binding affinity with 5-HT2A  neuroreceptors (Ki=6nm), with lesser affinity for the 5-HT1A, 5-HT1D and 5-HT2C subtypes. Recently, studies have highlighted the potential for low-dose psilocybin administration to exert a positive therapeutic antidepressant effect. This is likely associated with the modulatory effect that psilocybin (and psilocin) has on the serotonergic pathways, with serotonin a known contributor to mood regulation. Various clinical trials are currently underway, investigating the possible use of psilocybin in a medical setting for several mood disorders. A link to these can be found below:

 

https://clinicaltrials.gov/ct2/results?cond=&term=psilocybin&cntry=&state=&city=&dist=

 

 

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