Chemistry:2-Oxo-3-hydroxy-LSD

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2-Oxo-3-hydroxy-LSD, or 2-oxy-3-hydroxy-LSD, also known as O-H-LSD or OH-LSD, as well as more fully as 2-oxo-3-hydroxy-2,3-dihydro-LSD, is a lysergamide and the major metabolite of the psychedelic drug lysergic acid diethylamide (LSD).[1][2][3][4][5] LSD is eliminated 13% as O-H-LSD in urine within 24 hours[6] and urinary concentrations of O-H-LSD are 4 to 40 times those of LSD in humans.[7][3][8][9]

The specific enzymes responsible for the formation of O-H-LSD from LSD are unclear.[6][8][9][3] However, subsequent research found involvement of several cytochrome P450 enzymes.[10] O-H-LSD is thought to form from other LSD metabolites like 2-oxo-LSD and 3-hydroxy-LSD.[7][3][8][9][11]

It is unknown whether O-H-LSD is pharmacologically active or produces hallucinogenic effects.[6][5] However, O-H-LSD showed profoundly reduced albeit still detectable activity at the serotonin 5-HT2 receptors, including the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, compared to LSD in vitro.[10]

O-H-LSD was first described in the scientific literature by at least the 1990s.[12][13] It started being sold online as an analytical standard by 2024.[5]

See also

References

  1. ↑ "Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)". ACS Chemical Neuroscience 9 (10): 2331–2343. October 2018. doi:10.1021/acschemneuro.8b00043. PMID 29461039. https://shaunlacob.com/wp-content/uploads/2020/12/DC-LSD.pdf. 
  2. ↑ "The pharmacology of lysergic acid diethylamide: a review". CNS Neuroscience & Therapeutics 14 (4): 295–314. 2008. doi:10.1111/j.1755-5949.2008.00059.x. PMID 19040555. 
  3. ↑ 3.0 3.1 3.2 3.3 "Indolealkylamines: biotransformations and potential drug-drug interactions". The AAPS Journal 10 (2): 242–253. June 2008. doi:10.1208/s12248-008-9028-5. PMID 18454322. 
  4. ↑ Dolder P (2017). The Pharmacology of d-Lysergic Acid Diethylamide (LSD) (PDF) (Thesis). University of Basel. doi:10.5451/UNIBAS-006786123.
  5. ↑ 5.0 5.1 5.2 "3-Гидрокси-2-оксо-ЛСД (2-oxo-3-hydroxy-LSD)" (in ru). 10 November 2015. https://aipsin.com/newsubstance/1551/. 
  6. ↑ 6.0 6.1 6.2 "Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans". The International Journal of Neuropsychopharmacology 19 (1). June 2015. doi:10.1093/ijnp/pyv072. PMID 26108222. "In the present study, 13% of the orally administered LSD was recovered from urine as O-H-LSD within 24 hours. LSD is metabolized to O-H-LSD by cytochrome P450 enzymes, but the specific enzymes and mechanisms are unknown (Klette et al., 2000). To our knowledge, it is unknown whether O-H-LSD is pharmacologically active.". 
  7. ↑ 7.0 7.1 The Pharmacology of LSD. OUP/Beckley Foundation Press. 10 June 2010. p. 29. ISBN 978-0-19-958982-1. https://books.google.com/books?id=KTyC-e7NmI8C&pg=PA29. "Fig. 2.7 Metabolites of LSD. [...]" 
  8. ↑ 8.0 8.1 8.2 "Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse". Pharmacogenomics 12 (2): 215–233. February 2011. doi:10.2217/pgs.10.171. PMID 21332315. "It is rapidly metabolized to the following five metabolites which have been identified in urine or blood from human users: N-demethyl-LSD (nor-LSD), 2-oxo-LSD, 2-oxo-3-hydroxy-LSD, 13-hydroxyLSD and 14-hydroxy-LSD [187–189]. The 13- and 14-hydroxy metabolites are additionally excreted as glucuronides [188]. However, 2-oxo-LSD may be an intermediate in the formation of 2-oxo-3-hydroxy-LSD. Following the incubation of LSD with HLM and hepatocytes, 2,3-dihydroxy-LSD could be identified [190]. 2-oxo-3-hydroxy-LSD was shown to be the main human urinary metabolite with concentrations four- to 40-times higher than that of LSD [187,188,191]. As concluded by Yu in his review on indolalkylamines, almost nothing is known regarding the contribution of specific drug-metabolizing enzymes to the production of individual LSD metabolites in humans.". 
  9. ↑ 9.0 9.1 9.2 "Drugs of Abuse (Including Designer Drugs)". Metabolism of Drugs and Other Xenobiotics. Wiley. 18 April 2012. pp. 429–463. doi:10.1002/9783527630905.ch16. ISBN 978-3-527-32903-8. "It is metabolized to the following five metabolites: N-demethyl-LSD (nor-LSD), 2-oxo-LSD, 2-oxo-3-hydroxy-LSD, 13-hydroxy-LSD, and 14-hydroxy-LSD [72–74]. The 13- and 14-hydroxy metabolites are additionally excreted as glucuronides [74]. 2-Oxo-3-hydroxy-LSD was shown to be the main human urinary metabolite with concentrations 4–40 times higher than that of LSD [73–75]. In incubations of LSD with human liver microsomes and hepatocytes, 2,3-dihydroxy-LSD could be identified [71]. So far, the contribution and importance of specific enzymes in the formation of the LSD main metabolites such as 2-oxo-3-hydroxy-LSD still remains unclear." 
  10. ↑ 10.0 10.1 "Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use". Biochemical Pharmacology 164: 129–138. June 2019. doi:10.1016/j.bcp.2019.04.013. PMID 30981875. 
  11. ↑ "Metabolism of lysergic acid diethylamide (LSD): an update". Drug Metabolism Reviews 51 (3): 378–387. August 2019. doi:10.1080/03602532.2019.1638931. PMID 31266388. "In vitro studies using liver microsomes and human cryopreserved hepatocytes showed that O-HLSD is a product of LSD biotransformation whose amount increases in a time-dependent manner. In the same study was detected another metabolite in a time-dependent manner upon incubation, the dihydroxy-LSD (Klette et al. 2000). Therefore, LSD is oxidized to 2-oxo-LSD, which undergoes subsequent hydroxylation to O-H-LSD. Although the formation of O-H-LSD may occur via intermediate metabolite dihydroxy-LSD (Figure 1) (Klette et al. 2002).". 
  12. ↑ "Détection de l'acide lysergique diéthylamide (LSD) dans l'urine humaine: élimination, dépistage et confirmation analytique" (in French). Schweizerische Medizinische Wochenschrift 121 (50): 1887–1890. December 1991. PMID 1759150. 
  13. ↑ "New synthesis and characterization of (+)-lysergic acid diethylamide (LSD) derivatives and the development of a microparticle-based immunoassay for the detection of LSD and its metabolites". Bioconjugate Chemistry 8 (6): 896–905. 1997. doi:10.1021/bc9700594. PMID 9404664. 



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