The metabolism of psilocybin (and psilocin) is frequently cited. But, the supporting references are seldom discussed.
The available literature supports the following conclusions:
- Upon ingestion, psilocybin is metabolized to psilocin, which is the active molecule, responsible for the psychedelic effects of “magic mushrooms.”
- Psilocybin is dephosphorylated by alkaline phosphatase, producing psilocin, which is the active metabolite. Psilocin is responsible for the psychoactive properties – not psilocybin.
- Psilocin is further metabolized, resulting in psilocin-O-glucuronide as the main urinary metabolite.
Summary of Psilocybin Metabolism Studies
Below are some additional details from the literature cited in the References section below.
- In a clinical study investigating the metabolism of psilocybin and elimination kinetics of psilocin, eight volunteers received psilocybin in psychoactive oral doses of 212+ or -25 ug/kg body weight.
- Orally administered psilocybin was rapidly metabolized to psilocin.
- Urine was collected for 24 hr and psilocin concentrations were determined by high-performance liquid chromatography with column switching and electrochemical detection (HPLC-ECD).
- Notably, psilocybin was administered and psilocin urine concentrations were subsequently followed.
- Sample workup included “protection of the unstable psilocin with ascorbic acid,” freeze-drying, and extraction with methanol.
- One unanswered question is whether the “unstable psilocin” is responsible for the “bluing reaction” observed in some psilocybin-containing mushrooms?
- Stabilizing psilocin with ascorbic acid suggests that the degradation of psilocin proceeds via an oxidative mechanism. (Ascorbic acid, an antioxidant “protects” against oxidation.)
- Peak psilocin concentrations up to 870 ug/l were measured in urine samples during the 2-4 hr collection interval.
- Psilocybin and psilocin were metabolized and excreted within 24 hours of orally administering psilocybin.
- The psilocin excretion rate during this period was 55.5 (+/-33.8) ug/h.
- The limit of quantitation (10 ug/L) was usually reached 24 hr after drug administration.
While some work has been done to elucidate the metabolism and pharmacology of psilocybin/psilocin, the rest of the structurally similar derivatives have been ignored. This leaves lingering questions as to whether they behave similarly to psilocybin/psilocin — or if there are important differences in terms of pharmacology and/or metabolism.
The scientific community has yet to study the pharmacology of psilocybin derivatives other than psilocin and psilocybin. For example, is baeocystin active? Or does it function as a prodrug like psilocybin? How does its potency compare to the potency of psilocybin/psilocin? How do its metabolism and elimination compare to that for psilocybin/psilocin?