Metabolism of Lysergic Acid Diethylamide (LSD) to 2-Oxo-3-Hydroxy LSD (O-H-LSD)in Human Liver Microsomes and Cryopreserved Human Hepatocytes
Journal of Analytical Toxicology – October 01, 2000
Source: OpenAlex
Summary
Lysergic acid diethylamide (LSD) is metabolized to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD), which appears in human urine at concentrations 16-43 times higher than LSD. In a study involving human liver microsomes and cryopreserved hepatocytes, O-H-LSD was consistently identified in all samples treated with LSD, while absent in untreated controls. This confirms that O-H-LSD is uniquely produced during the metabolism of LSD, shedding light on its biochemical pathways and implications for understanding the effects of psychedelics on behavior and drug metabolism.
Abstract
The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.