Metabolism of Lysergic Acid Diethylamide (LSD) to 2-Oxo-3-Hydroxy LSD (O-H-LSD)in Human Liver Microsomes and Cryopreserved Human Hepatocytes
K. L. Klette, Carolyn J. Anderson, Gregory K. Poch, Alison Nimrod, Mahmoud A. Elsohly
Journal of Analytical Toxicology October 1, 2000 DOI: 10.1093/jat/24.7.550 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro laboratory study Peer reviewed |
|---|---|
| Population | Human liver microsomes and cryopreserved human hepatocytes |
| Intervention | LSD |
| Topics | LSD |
| Keywords | Microsome Urine Chromatography Hepatocyte Drug metabolism Biochemistry In vivo |
| Citations | 38 |
| Key points | O-H-LSD is definitively produced as a metabolic product of LSD in human liver microsomes and hepatocytes. |
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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 9
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans The International Journal of Neuropsychopharmacology June 24, 2015
- Absorption, Distribution, Metabolism and Excretion Pharmacogenomics of Drugs of Abuse Pharmacogenomics February 1, 2011
- Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD) ACS Chemical Neuroscience February 20, 2018
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