Psilocin, the active compound from magic mushrooms, is metabolized mainly by the enzyme monoamine oxidase A (MAO-A) in the liver and other organs. The Phase I metabolic pathway produces a newly identified intermediate, 2-(4-hydroxy-1H-indol-3-yl)-acetaldehyde (4-HIA), which is then converted to the terminal metabolite 2-(4-hydroxy-1H-indol-3-yl)-acetic acid (4-HIAA) by aldehyde oxidase and aldehyde dehydrogenases. MAO-A-mediated hepatic clearance accounts for 80.9% of total hepatic metabolism, but extrahepatic clearance is substantial, with total MAO-A-mediated organ clearance estimated at 614.81 mL/min, indicating that MAO-A plays a major role both in the liver and elsewhere in the body.
Detecting LSD use through urinalysis is difficult because LSD is rapidly metabolized and rarely appears in urine. Instead, its primary metabolite 2-oxo-3-hydroxy-LSD is usually detected. In this study, iso-LSD, a contaminant from illicit LSD preparation, was found alongside 2-oxo-3-hydroxy-LSD in many urine samples, often at higher abundance. Metabolism experiments with human liver microsomes showed that iso-LSD breaks down more slowly than LSD, and analysis of 24 authentic urine samples detected iso-LSD in 18 of them, sometimes with traces of a possible metabolite. The slower metabolism and high detection rate suggest iso-LSD is a viable urinary biomarker for confirming LSD consumption, especially when LSD or 2-oxo-3-hydroxy-LSD are absent.