Skip to main content

Metabolism and toxicological analyses of hallucinogenic tryptamine analogues being abused in Japan

Abstract

Hallucinogenic tryptamine analogues, an important class of drugs of abuse, can be naturally occurring or chemically synthesized compounds. In Japan, psilocin and psilocybin (ingredients of “magic mushrooms”) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT; a synthetic tryptamine) seem to be particularly problematic due to their extensive abuse. This review is focused on human metabolism and forensic toxicological analyses of the above three tryptamine analogues. In humans, psilocybin is rapidly dephosphorylated to form psilocin, and most of the psilocin is eventually conjugated to form its glucuronide. On the other hand, 5-MeO-DIPT is mainly metabolized via O-demethylation, 6-hydroxylation, and N-deisopropylation, partly followed by conjugation to form their sulfates and glucuronides. Suitable hydrolysis should be, therefore, applied for sensitive and effective analysis of the metabolites. In analyzing psilocin and psilocybin by gas chromatography-mass spectrometry (GC-MS), derivatization is necessary for their discriminative identification. Although 5-MeO-DIPT and its three major metabolites can be analyzed by GC-MS without any derivatization, trimethylsilyl derivatization provides improvement of their peak shapes and intensities. In contrast to GC-MS, liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry allow us not only to discriminate psilocin and psilocybin without derivatization, but also to directly analyze their conjugated metabolites.

This is a preview of subscription content, access via your institution.

References

  1. Fantegrossi WE, Murnane KS, Reissig CJ (2008) The behavioral pharmacology of hallucinogens. Biochem Pharmacol 75:17–33

    Article  CAS  PubMed  Google Scholar 

  2. Hofmann A, Heim R, Brack A, Kobel H (1958) Psilocybin, ein psychotroper Wirkstoff aus dem mexikanischen Rauschpilz Psilocybe mexicana Heim. Experientia 14:107–109

    Article  CAS  PubMed  Google Scholar 

  3. Shulgin AT, Carter MF (1980) N,N-Diisopropyltryptamine (DIPT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeODIPT). Two orally active tryptamine analogs with CNS activity. Commun Psychopharmacol 4:363–369

    CAS  PubMed  Google Scholar 

  4. Uchiyama N, Kikura-Hanajiri R, Kawahara N, Goda Y (2009) Identification of a cannabimimetic indole as a designer drug in a herbal product. Forensic Toxicol 27:61–66

    Article  CAS  Google Scholar 

  5. Kikura-Hanajiri R, Kawamura M, Maruyama T, Kitajima M, Takayama H, Goda Y (2009) Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragyna speciosa) by LC-ESI-MS. Forensic Toxicol 27:67–74

    Article  CAS  Google Scholar 

  6. Kamata T, Nishikawa M, Katagi M, Tsuchihashi H (2003) Optimized glucuronide hydrolysis for the detection of psilocin in human urine samples. J Chromatogr B 796:421–427

    Article  CAS  Google Scholar 

  7. Kamata T, Nishikawa M, Katagi M, Tsuchihashi H (2006) Direct detection of serum psilocin glucuronide by LC/MS and LC/MS/MS: time-courses of total and free (unconjugated) psilocin concentrations in serum specimens of a “magic mushroom” user. Forensic Toxicol 24:36–40

    Article  CAS  Google Scholar 

  8. Kamata T, Katagi M, Kamata HT, Miki A, Shima N, Zaitsu K, Nishikawa M, Tanaka E, Honda K, Tsuchihashi H (2006) Metabolism of the psychotomimetic tryptamine derivative 5-methoxy-N,N-diisopropyltryptamine in humans: identification and quantification of its urinary metabolites. Drug Metab Dispos 34:281–287

    Article  CAS  PubMed  Google Scholar 

  9. Kamata T, Katagi M, Kamata H, Miki A, Shima N, Zaitsu K, Nishikawa M, Tsuchihashi H (2007) Urinary excretion profiles of 5-methoxy-N,N-diisopropyltryptamine and its relevant metabolites in humans. J Health Sci 53:585–590

    Article  CAS  Google Scholar 

  10. Horita A, Weber LJ (1961) The enzymic dephosphorylation and oxidation of psilocybin and psilocin by mammalian tissue homogenates. Biochem Pharmacol 7:47–54

    Article  CAS  PubMed  Google Scholar 

  11. Horita A, Weber LJ (1962) Dephosphorylation of psilocybin in the intact mouse. Toxicol Appl Pharmacol 4:730–737

    Article  CAS  PubMed  Google Scholar 

  12. Sticht G, Käferstein H (2000) Detection of psilocin in body fluids. Forensic Sci Int 113:403–407

    Article  CAS  PubMed  Google Scholar 

  13. Grieshaber AF, Moore KA, Levine B (2001) The detection of psilocin in human urine. J Forensic Sci 46:627–630

    CAS  PubMed  Google Scholar 

  14. Hasler F, Bourquin D, Brenneisen R, Bär T, Vollenweider FX (1997) Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv 72:175–184

    Article  CAS  PubMed  Google Scholar 

  15. Hasler F, Bourquin D, Brenneisen R, Vollenweider FX (2002) Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. J Pharm Biomed Anal 30:331–339

    Article  CAS  PubMed  Google Scholar 

  16. Lindenblatt H, Kramer E, Holzmann-Erens P, Gouzoulis-Mayfrank E, Kovar KA (1998) Quantitation of psilocin in human plasma by high-performance liquid chromatography and electrochemical detection: comparison of liquid-liquid extraction with automated on-line solid-phase extraction. J Chromatogr B 709:255–263

    Article  CAS  Google Scholar 

  17. Meatherall R, Sharma P (2003) Foxy, a designer tryptamine hallucinogen. J Anal Toxicol 27:313–317

    CAS  PubMed  Google Scholar 

  18. Wilson JM, McGeorge F, Smolinske S, Meatherall R (2005) A foxy intoxication. Forensic Sci Int 148:31–36

    Article  CAS  PubMed  Google Scholar 

  19. Narimatsu S, Yonemoto R, Saito K, Takaya K, Kumamoto T, Ishikawa T, Asanuma M, Funada M, Kiryu K, Naito S, Yoshida Y, Yamamoto S, Hanioka N (2006) Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes. Biochem Pharmacol 71:1377–1385

    Article  CAS  PubMed  Google Scholar 

  20. Shima N, Kamata T, Kamata H, Zaitsu K, Katagi M, Tsuchihashi H (2007) Determination of 5-MeO-MIPT and its metabolites in blood and urine. Abstracts of the 127th Annual Meeting of The Pharmaceutical Society of Japan, 28P1-pm231 (CD-ROM)

  21. Katagi M, Kamata T, Tsuchihashi H (2009) Identification of major urinary metabolites of tryptamine-derived hallucinogens. Abstracts of the 57th Annual Conference on Mass Spectrometry, Osaka, Japan, pp. 266–267

  22. Chamakura RP (1994) Tryptamines. Microgram 27:316–329

    Google Scholar 

  23. Keller T, Schneider A, Regenscheit P, Dirnhofer R, Rücker T, Jaspers J, Kisser W (1999) Analysis of psilocybin and psilocin in Psilocybe subcubensis GUZMÄN by ion mobility spectrometry and gas chromatography-mass spectrometry. Forensic Sci Int 99:93–105

    Article  CAS  PubMed  Google Scholar 

  24. Vorce SP, Sklerov JH (2004) A general screening and confirmation approach to the analysis of designer tryptamines and phenethylamines in blood and urine using GC-EIMS and HPLC-electrospray-MS. J Anal Toxicol 28:407–410

    CAS  PubMed  Google Scholar 

  25. Kamata T, Nishikawa M, Katagi M, Tsuchihashi H (2005) Liquid chromatography-mass spectrometric and liquid chromatography-tandem mass spectrometric determination of hallucinogenic indoles psilocin and psilocybin in “magic mushroom” samples. J Forensic Sci 50:336–340

    Article  CAS  PubMed  Google Scholar 

  26. Tanaka E, Kamata T, Katagi M, Tsuchihashi H, Honda K (2006) A fatal poisoning with 5-methoxy-N,N-diisopropyltryptamine, Foxy. Forensic Sci Int 163:152–154

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tooru Kamata.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kamata, T., Katagi, M. & Tsuchihashi, H. Metabolism and toxicological analyses of hallucinogenic tryptamine analogues being abused in Japan. Forensic Toxicol 28, 1–8 (2010). https://doi.org/10.1007/s11419-009-0087-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11419-009-0087-9

Keywords

  • Hallucinogenic tryptamines
  • Indole derivatives
  • Psilocin
  • Psilocybin
  • 5-Methoxy-N,N-diisopropyltryptamine
  • Designer drug