Forensic Toxicology

, Volume 29, Issue 1, pp 25–37 | Cite as

Identification and quantitation of two cannabimimetic phenylacetylindoles JWH-251 and JWH-250, and four cannabimimetic naphthoylindoles JWH-081, JWH-015, JWH-200, and JWH-073 as designer drugs in illegal products

  • Nahoko Uchiyama
  • Maiko Kawamura
  • Ruri Kikura-Hanajiri
  • Yukihiro GodaEmail author
Original Article


Six cannabimimetic indoles have been identified as adulterants in herbal or chemical products being sold illegally in Japan, with four of the compounds being new as adulterants to our knowledge. The identifications were based on analyses using gas chromatography–mass spectrometry, liquid chromatography–mass spectrometry, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy. The first two compounds were identified as phenylacetyl indoles JWH-251 (2-(2-methylphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone; 1) and its demethyl-methoxylated analog JWH-250 (2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone; 2). Compound 2 was identical to that found as an adulterant in the UK and in Germany in 2009. The third compound was naphthoylindole JWH-081 (1-(4-methoxynaphthalenyl)-(1-pentyl-1H-indol-3-yl)methanone; 3), and the fourth was JWH-073 (1-naphthalenyl(1-butyl-1H-indol-3-yl)methanone; 4), which had been identified as an adulterant in our previous study. Two additional compounds were JWH-015 (1-naphthalenyl(2-methyl-1-propyl-1H-indol-3-yl)methanone; 5) and JWH-200 (1-naphthalenyl(1-(2-(4-morpholinyl)ethyl)-1H-indol-3-yl)methanone; 6). Compounds 14 and 6 were reported to be synthetic cannabinoids with selective affinity for cannabinoid CB1 receptors, while compound 5 was reported to be a selective CB2 receptor agonist causing immunosuppressive effects without psychotropic affects. One product contained both CB1 and CB2 receptor agonists in our collection. Quantitative analyses of the six cannabimimetic compounds in 20 products revealed that there was large variation in concentrations of the detected compounds among products; for herbal cutting products, the total amounts of these cannabinoids ranged from 26 to 100 mg.


JWH-251 JWH-081 JWH-015 JWH-200 Synthetic cannabinoid Designer drug 



Part of this work was supported by a Health and Labor Sciences Research Grant from the Ministry of Health, Labour, and Welfare, Japan.


  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 57:439–441CrossRefPubMedGoogle Scholar
  2. 2.
    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 27:61–66CrossRefGoogle Scholar
  3. 3.
    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 27:67–74CrossRefGoogle Scholar
  4. 4.
    Uchiyama N, Kikura-Hanajiri R, Ogata J, Goda Y (2010) Chemical analysis of synthetic cannabinoids as designer drugs in herbal products. Forensic Sci Int 198:31–38CrossRefPubMedGoogle Scholar
  5. 5.
    Kikuchi H, Uchiyama N, Ogata J, Kikura-Hanajiri R, Goda Y (2010) Chemical constituents and DNA sequence analysis of a psychotropic herbal product. Forensic Toxicol 28:77–83CrossRefGoogle Scholar
  6. 6.
    Auwärter V, Dresen S, Weinmann W, Müller M, Pütz M, Ferreirós N (2009) ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom 44:832–837CrossRefPubMedGoogle Scholar
  7. 7.
    Lindigkeit R, Boehme A, Eiserloh I, Luebbecke M, Wiggermann M, Ernst L, Beuerle T (2009) Spice: a never ending story? Forensic Sci Int 191:58–63CrossRefPubMedGoogle Scholar
  8. 8.
    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
  9. 9.
    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
  10. 10.
    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
  11. 11.
    Thomas BF, Compton DR, Martin BR (1990) Characterization of the lipophilicity of natural and synthetic analogs of delta 9-tetrahydrocannabinol and its relationship to pharmacological potency. J Pharmacol Exp Ther 255:624–630PubMedGoogle Scholar
  12. 12.
    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 40:471–478CrossRefPubMedGoogle Scholar
  13. 13.
    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
  14. 14.
    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 60:133–140CrossRefPubMedGoogle Scholar
  15. 15.
    Huffman JW (1999) Cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 6:705–720PubMedGoogle Scholar
  16. 16.
    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 11:539–549CrossRefPubMedGoogle Scholar
  17. 17.
    Zweiundzwanzigste Verordnung, zur Änderung betäubungsmittelrechtlicher Vorschriften (2009) Germany. BGBl I Nr. 3 vom 21.01.2009, 22. BtMÄndV vom 19. January 2009, S. 49–50. Accessed January 2009
  18. 18.
    EMCDDA (2009) EMCDDA action on new drugs briefing paper: understanding the ‘Spice’ phenomenon (a report from an EMCDDA expert meeting, 6 March 2009, Lisbon).—%20final%20version.pdf. Accessed April 2010
  19. 19.
    Huffman JW (2009) Cannabimimetic indoles, pyrroles, and indenes: structure–activity relationships and receptor interactions. In: Reggio PH (ed) The cannabinoid receptors. Humana Press, New York, pp 49–94CrossRefGoogle Scholar
  20. 20.
    Huffman JW, Szklennik PV, Almond A, Bushell K, Selley DE, He H, Cassidy MP, Wiley JL, Martin BR (2005) 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles. Bioorg Med Chem Lett 15:4110–4113CrossRefPubMedGoogle Scholar
  21. 21.
    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 128:971–979CrossRefPubMedGoogle Scholar
  22. 22.
    Huffman JW, Wu M, Lu J (1998) A very facile SNAr reaction with elimination of methoxide. J Org Chem 63:4510–4514CrossRefGoogle Scholar
  23. 23.
    Compton DR, Gold LH, Ward SJ, Balster RL, Martin BR (1992) Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther 263:1118–1126PubMedGoogle Scholar
  24. 24.
    Showalter VM, Compton DR, Martin BR, Abood ME (1996) Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands. J Pharmacol Exp Ther 278:989–999PubMedGoogle Scholar
  25. 25.
    Huffman JW, Padgett LW (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 121:1395–1411CrossRefGoogle Scholar

Copyright information

© Japanese Association of Forensic Toxicology and Springer 2010

Authors and Affiliations

  • Nahoko Uchiyama
    • 1
  • Maiko Kawamura
    • 1
  • Ruri Kikura-Hanajiri
    • 1
  • Yukihiro Goda
    • 1
    Email author
  1. 1.National Institute of Health SciencesTokyoJapan

Personalised recommendations