 Psilocybin is metabolized mostly in the liver. As it becomes converted to psilocin, it undergoes a first-pass effect, whereby its concentration is greatly reduced before it reaches the systemic circulation. Psilocin is broken down by the enzyme monoamine oxidase to produce several metabolites that can circulate in the blood plasma, including 4-hydroxyindole-3-acetaldehyde, 4-hydroxytryptophol, and 4-hydroxyindole-3-acetic acid. Some psilocin is not broken down by enzymes and instead forms a glucuronide; this is a biochemical mechanism animals use to eliminate toxic substances by linking them with glucuronic acid, which can then be excreted in the urine. Psilocin is glucuronated by the glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine. Based on studies using animals, about 50 % of ingested psilocybin is absorbed through the stomach and intestine. Within 24 hours, about 65 % of the absorbed psilocybin is excreted into the urine, and a further 15 – 20 % is excreted in the bile and feces. Although most of the remaining drug is eliminated in this way within 8 hours, it is still detectable in the urine after 7 days. Clinical studies show that psilocin concentrations in the plasma of adults average about 8 µg / liter within 2 hours after ingestion of a single 15 mg oral psilocybin dose; psychological effects occur with a blood plasma concentration of 4 – 6 µg / liter. Psilocybin is about 100 times less potent than LSD on a weight per weight basis, and the physiological effects last about half as long.
