A Brief Review of the Pharmacology of Psilocybin Cameron Behram Abstract: Following a decades-long hiatus in research after its classification as a Schedule I drug in the United States, psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine) has become a new area of interest for those researching potential psychotherapeutic adjuncts. This article will briefly review the known pharmacology of psilocybin, as well as its pharmacokinetic and pharmacodynamic potential to both supplement therapeutic exercises in mentally ill individuals as well as help scientists better understand neurological mechanisms of sensory processing and even human consciousness as a whole due to its alteration in states of consciousness. Introduction: Psilocin, the psychoactive metabolite of the psilocybin found in psilocybin mushrooms (colloquially known as “magic mushrooms”) is a serotonergic hallucinogen that has recently become a focal point in the research of psychotherapeutic adjuncts. The use of psilocybin-containing mushrooms dates back to the Aztec Empire in shamanic and divinatory practices,1 but it was first chemically isolated by the now-famous Swiss chemist Albert Hoffman in 1957 and synthetically manufactured in 1958, when it was sold as an experimental psychotherapeutic adjunct under the name Indocybin® Sandoz after thorough human and animal testing.2 It has since been classified as a Schedule I drug in the United States, meaning that it has “no currently accepted medical use and a high potential for abuse”3, according to the United States Drug Enforcement Agency. This classification led to a 25-year-long gap in 7
research, until several breakthrough studies of psilocybin’s potential medical use drew attention from the scientific community, thus leading to a revival in both public and scientific interest in hallucinogens.4 The pharmacokinetics of psilocybin is now welldocumented, but vast amounts of research are being conducted to further understand its potential pharmacological uses to both ameliorate mental illness and better understand the mechanisms of the human brain due to its potent effects that alter the human state of consciousness. Pharmacokinetics of psilocin: Pharmacokinetics generally refers to the branch of pharmacology concerning a drug’s given mechanism of action and its physiological impacts on the human body. Recently, the scientific community has gained a comparatively thorough understanding of the pharmacokinetic mechanisms of psilocybin and psilocin through the use of modern brain imaging techniques. Upon oral ingestion of psilocybin, approximately 50% of it was actually absorbed into the bloodstream (calculated through isotropic labelling of the 14th carbon in psilocybin). Following absorption into the bloodstream, the psilocybin is enzymatically converted into 4 primary metabolites through a hepatic mechanism using the alkaline phosphatase enzyme. These metabolites consist of psilocin (4-hydroxy-N,N-dimethyltryptamine), which constitutes the primary metabolic product of psilocybin, which is further metabolized into 4-hydroxyindole-3yl-acetaldehyde, then into 4-hydroxyindole3-yl-acetic-acid and 4-hydroxytryptophol, which are largely clinically insignificant.2 The only clinically significant metabolite of psilocin is psilocin-O-glucuronide, which is the main urinary metabolite of psilocin and can be used to detect the presence of the drug.5 The specific metabolic pathway for psilocybin is pictured in Figure 1.
