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

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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.

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References

  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)

  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: 995–1004

    PubMed  CAS  Google Scholar 

  3. Huffman JW (1999) Cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 6: 705–720

    PubMed  CAS  Google Scholar 

  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: 133–140

    Article  PubMed  CAS  Google Scholar 

  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: 539–549

    Article  PubMed  CAS  Google Scholar 

  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. 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: 971–979

    Article  PubMed  CAS  Google Scholar 

  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: 1230–1239

    Article  PubMed  CAS  Google Scholar 

  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: 297–302

    PubMed  CAS  Google Scholar 

  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: 605–613

    PubMed  CAS  Google Scholar 

  11. Huffman JW, Padgett LW (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 12: 1395–1411

    Article  PubMed  CAS  Google Scholar 

  12. Razdan RK (1986) Structure-activity relationships in cannabinoids. Pharmacol Rev 38: 75–149

    PubMed  CAS  Google Scholar 

  13. Rapaka RS, Makriyannis A (1987) Structure-activity relationships of the cannabinoids. NIDA Res Monogr 79: 1–216

    Google Scholar 

  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: 624–630

    PubMed  CAS  Google Scholar 

  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: 1008–1015

    PubMed  CAS  Google Scholar 

  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: 201–209

    PubMed  CAS  Google Scholar 

  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: 218–226

    PubMed  CAS  Google Scholar 

  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: 471–478

    Article  PubMed  CAS  Google Scholar 

  19. Howlett AC, Johnson MR, Melvin LS (1990) Classical and nonclassical cannabinoids: mechanism of action-brain binding. NIDA Res Monogr 96: 100–111

    PubMed  CAS  Google Scholar 

  20. Johnson MR, Melvin LS, Milne GM (1982) Prototype cannabinoid analgetics, prostaglandins and opiates-a search for points of mechanistic interaction. Life Sci 31: 1703–1706

    Article  PubMed  CAS  Google Scholar 

  21. Weissman A, Milne GM, Melvin LS (1982) Cannabimimetic activity from CP-47497, a derivative of 3-phenylcyclohexanol. J Pharmacol Exp Ther 223: 516–523

    PubMed  CAS  Google Scholar 

  22. Melvin LS, Johnson MR, Herbert CA, Milne GM, Weissman A (1984) A cannabinoid derived prototypical analgesic. J Med Chem 27: 67–71

    Article  PubMed  CAS  Google Scholar 

  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: 124–135

    Article  PubMed  Google Scholar 

  24. Huffman JW, Dai D, Martin BR, Compton DR (1994) Design, synthesis and pharmacology of cannabimimetic indoles. Bioorg Med Chem Lett 4: 563–566

    Article  Google Scholar 

  25. Maccarrone M (2008) Good news for CB1 receptors: endogenous agonists are in the right place. Br J Pharmacol 153: 179–181

    Article  PubMed  CAS  Google Scholar 

  26. Pacher P, Batkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58: 389–462

    Article  PubMed  CAS  Google Scholar 

  27. Kulkarni SK, Ninan I (2001) Current concepts in cannabinoid pharmacology. Indian J Pharmacol 33: 170–184

    CAS  Google Scholar 

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Correspondence to Yukihiro Goda.

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Uchiyama, N., Kikura-Hanajiri, R., Kawahara, N. et al. Identification of a cannabimimetic indole as a designer drug in a herbal product. Forensic Toxicol 27, 61–66 (2009). https://doi.org/10.1007/s11419-009-0069-y

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  • DOI: https://doi.org/10.1007/s11419-009-0069-y

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