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.
Similar content being viewed by others
References
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)
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
Huffman JW (1999) Cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 6: 705–720
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
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
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
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
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
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
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
Huffman JW, Padgett LW (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 12: 1395–1411
Razdan RK (1986) Structure-activity relationships in cannabinoids. Pharmacol Rev 38: 75–149
Rapaka RS, Makriyannis A (1987) Structure-activity relationships of the cannabinoids. NIDA Res Monogr 79: 1–216
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
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
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
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
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
Howlett AC, Johnson MR, Melvin LS (1990) Classical and nonclassical cannabinoids: mechanism of action-brain binding. NIDA Res Monogr 96: 100–111
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
Weissman A, Milne GM, Melvin LS (1982) Cannabimimetic activity from CP-47497, a derivative of 3-phenylcyclohexanol. J Pharmacol Exp Ther 223: 516–523
Melvin LS, Johnson MR, Herbert CA, Milne GM, Weissman A (1984) A cannabinoid derived prototypical analgesic. J Med Chem 27: 67–71
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
Huffman JW, Dai D, Martin BR, Compton DR (1994) Design, synthesis and pharmacology of cannabimimetic indoles. Bioorg Med Chem Lett 4: 563–566
Maccarrone M (2008) Good news for CB1 receptors: endogenous agonists are in the right place. Br J Pharmacol 153: 179–181
Pacher P, Batkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58: 389–462
Kulkarni SK, Ninan I (2001) Current concepts in cannabinoid pharmacology. Indian J Pharmacol 33: 170–184
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11419-009-0069-y