In humans, psilocybin functions as a prodrug (Dinis-Oliveira, 2017) and is rapidly dephosphorylated by the homodimeric protein enzyme alkaline phosphatase to psilocin (4-hydroxy-N,N-dimethyltryptamine, 4-OH-DMT), the psychoactive metabolite which acts as a non-selective partial 5-HT receptor agonist. It shows particularly high binding affinity for the 5-HT1A, 5-HT2A, and 5-HT2C receptor subtypes (Kraehenmann et al., 2015; Nichols, 2004).
In the final step of the pharmacokinetic elimination phase , psilocin in metabolized into psilocin-O-glucuronide which is the primary urinary metabolite which can be quantified by various clinical methods in urine (Grieshaber, Moore, & Levine, 2001; Kamata, Nishikawa, Katagi, & Tsuchihashi, 2003).
Table 1. Pharmakoknetics of psilocybin (adapted from Hasler, Bourquin, Brenneisen, & Vollenweider, 2002)