how is psilocybin metabolized?
To metabolize is to breakdown a chemical to its simpler component forms for cells to use. Psilocybin is a psychedelic compound found in fungi of several genera including Psilocybe, Panaeolus, and Copelandia. Inside the body, it influences the functional molecular mechanisms of several organs, mainly the brain, kidneys, and liver. On its own psilocybin is not as effective. To produce its infamous hallucinogenic effect in the brain, it must be converted to psilocin. Psilocin is the main active molecule, which is derived from the prodrug psilocybin.
There are two ways of getting these metabolites inside the body: oral ingestion (for example, eating the "magic mushrooms") and intravenous injection. When orally ingested, the mushrooms are digested in the usual way. Eventually, the psilocybin in the mushrooms reaches the liver where it is converted to psilocin. An enzyme, alkaline phosphatase, acts on psilocybin such that its phosphate group (PO₄³⁻) is replaced with a hydroxyl group (−OH). Psilocin is further acted upon by diverse enzymes to obtain products which are either excreted through urine or contribute to other functions in hepatocytes (liver cells) as psilocin metabolites.
There is a format to convert chemical equations to sentences. Nevertheless, I firmly believe that one must have the convenience of remembering their organic chemistry without having a stroke. Behold,
psilocin + monoamine oxidase = 4-hydroxyindole-3-acetaldehyde
psilocin + glucuronosyltransferase = psilocin glucoronide (PCG)
psilocin + aldehyde reductase = 4-hydroxytryptophol
psilocin + aldehyde dehydrogenase = 4-hydroxyindole-3-acetic acid (4HIAA)
The fates of each of these products are an elaborate article on their own, and I will be happy to write them should you be interested. Let me know!
Now, we remember that the primary effects due to which human beings consume psilocybin-containing mushrooms are caused by psilocin in the brain. The exact step-by-step mechanism has not yet been outlined; however, general molecular interactions have been found in studies. This psychoactive compound shows an interesting resemblance to serotonin the neurotransmitter. The psilocin binds to 5-HT2A (a molecule in a cell membrane which responds specifically to serotonin i.e., a serotonin receptor) with high affinity, which is believed to be essential for hallucinogenic effect. It also binds to other receptors with varying affinities, although their significance is yet to be understood.
Psilocybin and its metabolized products are completely removed from the body after 24 hours of consumption. The kidneys take pride in detoxifying circulating blood by creating the waste product urine; psilocin consumed can be detected in blood plasma 6-8 hours after consumption. Majority of the psilocin excreted through urine is in the form of psilocin-O-glucoronide. Psilocybin that remains psilocybin is also excreted through urine by the kidneys.
Introducing psilocybin in the body through veins produces effects of similar intensity as the former method. Whereas it remains as an active compound in the blood for a shorter duration. Turton et. al. conducted an fMRI (functional magnetic resonance imaging) study to compare the subjective experience of intravenous psilocybin injection interestingly explains how their participants’ descriptions of their experiences were influenced by the MRI scanner environment and the 1960s, when psychedelics were first introduced to western culture.
bibliography:
Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addiction biology. 2002 Oct;7(4):357-64.
Tylš F, Páleníček T, Horáček J. Psilocybin–summary of knowledge and new perspectives. European Neuropsychopharmacology. 2014 Mar 1;24(3):342-56.
Turton S, Nutt DJ, Carhart-Harris RL. A qualitative report on the subjective experience of intravenous psilocybin administered in an FMRI environment. Current Drug Abuse Reviews. 2014 Aug 1;7(2):117-27.
