Chemistry:14-Hydroxy-LSD

From HandWiki

14-Hydroxy-LSD is a lysergamide and a metabolite of the psychedelic drug lysergic acid diethylamide (LSD).[1][2][3][4][5][6] It is formed via aromatic hydroxylation at position 14 of the lysergic acid moiety and is subsequently excreted as a glucuronide conjugate.[1][2][3][6]

14-Hydroxy-LSD is a major metabolite of LSD in rats and guinea pigs, where it is excreted predominantly as a glucuronide in bile and urine.[1][2][7][5][8][9][10] In contrast, it appears only as a minor metabolite in rhesus monkeys and humans.[1][2][7][5][8][9] Studies using human liver microsomes and urine samples have confirmed its presence in humans, but in low concentrations that are often below quantification limits.[7][3][6]

The specific enzymes involved in the formation of hydroxylated LSD metabolites like 14-hydroxy-LSD remain unidentified.[5] As of 2016, David E. Nichols noted that the pharmacology of hydroxylated LSD metabolites, including 14-hydroxy-LSD, had not been studied.[11] Notably, 14-hydroxy-LSD does not induce LSD-like changes in the EEG of rabbits, in contrast to LSD and 13-hydroxy-LSD.[10]

14-Hydroxy-LSD was first reported in the scientific literature by at least 1975.[1][12][13][14]

See also

References

  1. 1.0 1.1 1.2 1.3 1.4 "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. "In animals, metabolism of LSD is highly species dependent...". 
  2. 2.0 2.1 2.2 2.3 "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. "The metabolism of [14C]-LSD has been investigated...". 
  3. 3.0 3.1 3.2 "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. "Furthermore, it seems to occur an aromatic hydroxylation...". 
  4. Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Wiley. 9 March 2012. pp. 452–466. doi:10.1002/9781118105955.ch22. ISBN 978-0-471-72760-6. "There are limited data on the metabolites of LSD in humans..." 
  5. 5.0 5.1 5.2 5.3 "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. https://onlinelibrary.wiley.com/doi/10.1002/9783527630905.ch16. Retrieved 30 June 2025. "It is metabolized to the following five metabolites..." 
  6. 6.0 6.1 6.2 "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. "LSD is rapidly metabolized in humans...". 
  7. 7.0 7.1 7.2 Dolder P (2017). The Pharmacology of d-Lysergic Acid Diethylamide (LSD) (PDF) (Thesis). University of Basel. doi:10.5451/UNIBAS-006786123. In rodents, the major metabolites...
  8. 8.0 8.1 "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. "LSD is extensively metabolized in laboratory animals...". 
  9. 9.0 9.1 "The hallucinogenic world of tryptamines: an updated review". Archives of Toxicology 89 (8): 1151–1173. August 2015. doi:10.1007/s00204-015-1513-x. PMID 25877327. Bibcode2015ArTox..89.1151A. https://psilosybiini.info/paperit/The%20hallucinogenic%20world%20of%20tryptamines,%20an%20updated%20review%20(Ara%FAjo%20et%20al.,%202015).pdf. "Major metabolites detected in the rat and guinea pigs urine...". 
  10. 10.0 10.1 "The fate of lysergic acid DI[14C]ethylamide ([14C]LSD) in the rat, guinea pig and rhesus monkey and of [14C]iso-LSD in rat". Biochemical Pharmacology 28 (20): 3093–3101. October 1979. doi:10.1016/0006-2952(79)90618-x. PMID 117811. "EEG studies...". 
  11. "Psychedelics". Pharmacological Reviews 68 (2): 264–355. April 2016. doi:10.1124/pr.115.011478. ISSN 0031-6997. PMID 26841800. "[...] It also seems possible that one of the metabolites of LSD...". 
  12. "The Fate of Lysergic Acid Di[14C]ethylamide ([14C]LSD) in the Rat". Biochemical Society Transactions 3 (2): 290–292. 1975. doi:10.1042/bst0030290. PMID 1132562. 
  13. "The fate of LSD in the body: forensic considerations". Journal - Forensic Science Society 18 (1–2): 89–98. 1978. doi:10.1016/s0015-7368(78)71189-8. PMID 105081. 
  14. "The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats". Experientia 32 (5): 616–617. May 1976. doi:10.1007/BF01990195. PMID 1278313.