Forensic Toxicology

, Volume 27, Issue 2, pp 61–66

Identification of a cannabimimetic indole as a designer drug in a herbal product

  • Nahoko Uchiyama
  • Ruri Kikura-Hanajiri
  • Nobuo Kawahara
  • Yukihiro Goda
Original Article

Abstract

A cannabimimetic indole has been identified as a new adulterant in a herbal product being sold illegally in Japan for its expected narcotic effect. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry analyses indicated that the product contained two major compounds. One was identified as a cannabinoid analog (1RS,3SR)-3-[4-(1,1-dimethyloctyl)-2-hydroxyphenyl]cyclohexan-1-ol (1) by direct comparison with the authentic compound, which we reported previously. The other compound (2) showed a molecular weight of 341 daltons, and accurate mass spectral measurements showed its elemental composition to be C24H23NO. Both mass and nuclear magnetic resonance spectrometric data revealed that 2 was 1-pentyl-3-(1-naphthoyl)indole [or naphthalen-1-yl-(1-pentylindol-3-yl)methanone] being identical to JWH-018, which was synthesized by Wiley and coworkers in 1998. This compound was reported as a potent cannabinoid receptor agonist possessing a pharmacological cannabimimetic activity.

Keywords

1-Pentyl-3-(1-naphthoyl)indole Naphthalen-1-yl-(1-pentylindol-3-yl)methanone JWH-018 Cannabimimetic indole Designer drug Herbal product 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Uchiyama N, Kikura-Hanajiri R, Kawahara N, Haishima Y, Goda Y (2009) Identification of a cannabinoid analog as a new type of designer drug in a herbal product. Chem Pharm Bull 57(4), (in press)Google Scholar
  2. 2.
    Wiley JL, Compton DR, Dai D, Lainton JA, Phillips M, Huffman JW, Martin BR (1998) Structure-activity relationships of indole- and pyrrole-derived cannabinoids. J Pharmacol Exp Ther 285: 995–1004PubMedGoogle Scholar
  3. 3.
    Huffman JW (1999) Cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 6: 705–720PubMedGoogle Scholar
  4. 4.
    Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR (2000) Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding. Drug Alcohol Depend 60: 133–140PubMedCrossRefGoogle Scholar
  5. 5.
    Huffman JW, Mabon R, Wu MJ, Lu J, Hart R, Hurst DP, Reggio PH, Wiley JL, Martin BR (2003) 3-Indolyl-1-naphthylmethanes: new cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB1 cannabinoid receptor. Bioorg Med Chem 11: 539–549PubMedCrossRefGoogle Scholar
  6. 6.
    Zweiundzwanzigste Verordnung, zur Änderung betäubungsmittelrechtlicher Vorschriften (2009), Germany. BGBl I Nr. 3 vom 21.01.2009, 22. BtMÄndV vom 19. Januar 2009, S. 49–50, http://www.bgblportal.de/BGBL/bgbl1f/bgbl109s0049.pdf. Accessed 19 Jan 2009
  7. 7.
    Kikura-Hanajiri R, Kawamura M, Uchiyama N, Ogata J, Kamakura H, Saisho K, Goda Y (2008) Analytical data of designated substances (Shitei-Yakubutsu) controlled by the Pharmaceutical Affairs Law in Japan, part I: GC-MS and LC-MS. Yakugaku Zasshi 128: 971–979PubMedCrossRefGoogle Scholar
  8. 8.
    Martin BR, Wiley JL, Beletskaya I, Sim-Selley LJ, Smith FL, Dewey WL, Cottney J, Adams J, Baker J, Hill D, Saha B, Zerkowski J, Mahadevan A, Razdan RK (2006) Pharmacological characterization of novel water-soluble cannabinoids. J Pharmacol Exp Ther 318: 1230–1239PubMedCrossRefGoogle Scholar
  9. 9.
    Howlett AC, Johnson MR, Melvin LS, Milne GM (1988) Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model. Mol Pharmacol 33: 297–302PubMedGoogle Scholar
  10. 10.
    Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34: 605–613PubMedGoogle Scholar
  11. 11.
    Huffman JW, Padgett LW (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 12: 1395–1411PubMedCrossRefGoogle Scholar
  12. 12.
    Razdan RK (1986) Structure-activity relationships in cannabinoids. Pharmacol Rev 38: 75–149PubMedGoogle Scholar
  13. 13.
    Rapaka RS, Makriyannis A (1987) Structure-activity relationships of the cannabinoids. NIDA Res Monogr 79: 1–216Google Scholar
  14. 14.
    Thomas BF, Compton DR, Martin BR (1990) Characterization of the lipophilicity of natural and synthetic analogs of ?9-tetrahydrocannabinol and its relationship to pharmacological potency. J Pharmacol Exp Ther 255: 624–630PubMedGoogle Scholar
  15. 15.
    Melvin LS, Milne GM, Johnson MR, Subramaniam B, Wilken GH, Howlett AC (1993) Structure-activity relationships for cannabinoid receptor-binding and analgesic activity: studies of bicyclic cannabinoid analogs. Mol Pharmacol 44: 1008–1015PubMedGoogle Scholar
  16. 16.
    Compton DR, Johnson MR, Melvin LS, Martin BR (1992) Pharmacological profile of a series of bicyclic cannabinoid analogs: classification as cannabimimetic agents. J Pharmacol Exp Ther 260: 201–209PubMedGoogle Scholar
  17. 17.
    Compton DR, Rice KC, De Costa BR, Razdan RK, Melvin LS, Johnson MR, Martin BR (1993) Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. J Pharmacol Exp Ther 265: 218–226PubMedGoogle Scholar
  18. 18.
    Martin BR, Compton DR, Thomas BF, Prescott WR, Little PJ, Razdan RK, Johnson MR, Melvin LS, Mechoulam R, Ward SJ (1991) Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol Biochem Behav 40: 471–478PubMedCrossRefGoogle Scholar
  19. 19.
    Howlett AC, Johnson MR, Melvin LS (1990) Classical and nonclassical cannabinoids: mechanism of action-brain binding. NIDA Res Monogr 96: 100–111PubMedGoogle Scholar
  20. 20.
    Johnson MR, Melvin LS, Milne GM (1982) Prototype cannabinoid analgetics, prostaglandins and opiates-a search for points of mechanistic interaction. Life Sci 31: 1703–1706PubMedCrossRefGoogle Scholar
  21. 21.
    Weissman A, Milne GM, Melvin LS (1982) Cannabimimetic activity from CP-47497, a derivative of 3-phenylcyclohexanol. J Pharmacol Exp Ther 223: 516–523PubMedGoogle Scholar
  22. 22.
    Melvin LS, Johnson MR, Herbert CA, Milne GM, Weissman A (1984) A cannabinoid derived prototypical analgesic. J Med Chem 27: 67–71PubMedCrossRefGoogle Scholar
  23. 23.
    D’Ambra TE, Estep KG, Bell MR, Eissenstat MA, Josef KA, Ward SJ, Haycock DA, Baizman ER, Casiano FM, Beglin NC, Chippari SM, Grego JD, Kullnig RK, Daley GT (1992) Conformationally restrained analogues of pravadoline: nanomolar potent, enantioselective, (aminoalkyl)indole agonists of the cannabinoid receptor. J Med Chem 35: 124–135PubMedCrossRefGoogle Scholar
  24. 24.
    Huffman JW, Dai D, Martin BR, Compton DR (1994) Design, synthesis and pharmacology of cannabimimetic indoles. Bioorg Med Chem Lett 4: 563–566CrossRefGoogle Scholar
  25. 25.
    Maccarrone M (2008) Good news for CB1 receptors: endogenous agonists are in the right place. Br J Pharmacol 153: 179–181PubMedCrossRefGoogle Scholar
  26. 26.
    Pacher P, Batkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58: 389–462PubMedCrossRefGoogle Scholar
  27. 27.
    Kulkarni SK, Ninan I (2001) Current concepts in cannabinoid pharmacology. Indian J Pharmacol 33: 170–184Google Scholar

Copyright information

© Japanese Association of Forensic Toxicology 2009

Authors and Affiliations

  • Nahoko Uchiyama
    • 1
  • Ruri Kikura-Hanajiri
    • 1
  • Nobuo Kawahara
    • 1
  • Yukihiro Goda
    • 1
  1. 1.National Institute of Health SciencesTokyoJapan

Personalised recommendations