Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH20322
REVIEW
Contents Vol 74(6)

Synthetic Cannabinomimetics: A Brief History and the Challenges They Pose for the Forensic Chemist

Michael Collins https://orcid.org/0000-0001-6423-0161 A
+ Author Affiliations
- Author Affiliations

A National Measurement Institute, 105 Delhi Road, North Ryde, NSW 2113, Australia. Email: michael.collins@measurement.gov.au




Michael Collins obtained his PhD in organic chemistry from the University of Sydney on the correlation between NMR spectral parameters and molecular structure under the guidance of Professor Sever Sternhell. He is currently the Director of the Australian Forensic Drug Laboratory, having spent more than 20 years working in forensic chemistry. He has served on national and international forensic science advisory panels and his main interest today is the application of NMR and mass spectroscopy to molecular structure determination of designer drugs.

Australian Journal of Chemistry 74(6) 405-415 https://doi.org/10.1071/CH20322
Submitted: 26 October 2020  Accepted: 11 January 2021   Published: 29 January 2021

Abstract

Since the first detection of synthetic cannabinomimetics in herbal smoking blends in 2008 the clandestine production of these compounds, based on seizure data, increased in number every year until ~2012. In recent years there has been a decline in synthetic cannabinomimetic production both in number and diversity. The synthetic details of the first generation cannabinoids were documented in the scientific and medical literature making production comparatively simple. Subsequent generations of synthetic cannabinoids involved more complex but still very practicable synthetic chemistry. This resulted in a period of rapid growth in synthetic cannabinoids creating a health crisis and problems for forensic chemists faced with many substances for which no certified reference materials existed. Routine forensic chemistry laboratories were well practiced at identifying known drugs using chromatographic–mass spectrometric techniques and comparison to reference materials. However as synthetic cannabinomimetics, often referred to in the literature as synthetic cannabinoids, appeared in large numbers, few laboratories were equipped with the nuclear magnetic resonance (NMR) spectrometers and high resolution mass spectrometers (HRMS) required for identification of unknown substances. These developments also challenged public prosecutors for opinions from forensic experts as to the legality or otherwise of these novel drugs.


References

[1]  S. Hudson, J. Ramsey, Drug Test. Anal. 2011, 3, 466.
         | Crossref | GoogleScholarGoogle Scholar | 21337724PubMed |

[2]  EMCDDA (European Monitoring Centre for Drugs and Drug Addiction), Thematic Paper: Understanding the ‘Spice’ phenomenon. Available at: http://www.emcdda.europa.eu/thematic-papers/spice (accessed 25 August 2020).

[3]  L. King, A. Kicman, Drug Test. Anal. 2011, 3, 401.
         | Crossref | GoogleScholarGoogle Scholar | 21780307PubMed |

[4]  S. Bannister, M. Conner, in Handbook of Experimental Pharmacology (Ed. J. E. Barrett) 2018, pp. 1–26 (Springer: Berlin).

[5]  J. W. Huffman, in The Cannabinoid Receptors (Ed. P. H. Reggio) 2009, pp. 49–94 (Humana Press: Totowa, NJ).

[6]  R. G. Pertwee, in Cannabinoids (Ed. R. Pertwee) 2005, pp. 1–51 (Springer Press: Heidelberg).

[7]  J. Wiley, D. Compton, D. Dai, J. Lainton, M. Phillips, J. Huffman, B. Martin, J. Pharmacol. Exp. Ther. 1998, 285, 995.
         | 9618400PubMed |

[8]  J. W. Huffman, S. G. Duncan, Bioorg. Med. Chem. Lett. 1997, 7, 2799.
         | Crossref | GoogleScholarGoogle Scholar |

[9]  D. R. Compton, M. R. Johnson, L. S. Melvin, B. R. Martin, J. Pharmacol. Exp. Ther. 1992, 260, 201.
         | 1309872PubMed |

[10]  United Nations Office on Drugs and Crime (UNODC), World Drug Report 2020.

[11]  Shorter Oxford English Dictionary (6th edn) 2007 (Oxford University Press: Oxford).

[12]  Australian New Zealand Policing Advisory Agencyhttps://www.anzpaa.org.au/forensic-science/forensic-sciences

[13]  United Nations Office on Drugs and Crime (UNODC)https://www.unodc.org/unodc/en/scientists/publications-drug-testing-laboratories.html

[14]  Scientific Working Group for the Analysis of Seized Drugs, SWGDRUG Homepage. Available at: http://swgdrug.org

[15]  M. Collins, Drug Test. Anal. 2011, 3, 404.
         | Crossref | GoogleScholarGoogle Scholar | 21755608PubMed |

[16]  R. Mechoulam, S. Ben-Shabat, Nat. Prod. Rep. 1999, 16, 131.
         | Crossref | GoogleScholarGoogle Scholar | 10331283PubMed |

[17]  R. Mechoulam, in Cannabinoids as Therapeutic Agents (Ed. R. Mechoulam) 1986, pp. 1–20 (CRC Press: Boca Raton, FL).

[18]  A. Galal, D. Slade, W. Gul, A. El-Alfy, D. Ferreira, M. Elsohly, Recent Patents CNS Drug Discov. 2009, 4, 112.
         | Crossref | GoogleScholarGoogle Scholar |

[19]  R. Mechoulam, in Marijuana, Chemistry, Metabolism, Pharmacology and Clinical Effects (Ed. R. Mechoulam) 1973, p. 119 (Academic Press: New York, NY).

[20]  Y. Gaoni, R. Mechoulam, J. Am. Chem. Soc. 1964, 86, 1646.
         | Crossref | GoogleScholarGoogle Scholar |

[21]  Y. Gaoni, R. Mechoulam, J. Am. Chem. Soc. 1965, 87, 3273.
         | 14324315PubMed |

[22]  E. C. Taylor, K. Lenard, Y. Shvo, J. Am. Chem. Soc. 1966, 88, 367.
         | Crossref | GoogleScholarGoogle Scholar |

[23]  K. E. Fahrenholtz, M. Lurie, R. W. Kierstead, J. Am. Chem. Soc. 1966, 88, 2079.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  R. Mechoulam, P. Braun, Y. Gaoni, J. Am. Chem. Soc. 1967, 89, 4552.
         | Crossref | GoogleScholarGoogle Scholar | 6046550PubMed |

[25]  A. Howlett, R. Fleming, Mol. Pharmacol. 1984, 26, 532.
         | 6092901PubMed |

[26]  L. Matsuda, S. Lolait, M. Brownstein, A. Young, I. Bonner, Nature 1990, 346, 561.
         | Crossref | GoogleScholarGoogle Scholar | 2165569PubMed |

[27]  W. A. Devane, L. Hanus, A. Breuer, R. G. Pertwee, L. A. Stevenson, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger, R. Mechoulam, Science 1992, 258, 1946.
         | Crossref | GoogleScholarGoogle Scholar | 1470919PubMed |

[28]  M. Bell, T. D’Ambra, V. Kumar, M. Eissenstat, J. Herrmann, J. Wetzel, D. Rosi, R. Philion, S. Daum, D. Hlasta, R. Kullnig, J. Ackerman, D. Haubrich, D. Luttinger, E. Baizman, M. Miller, S. Ward, J. Med. Chem. 1991, 34, 1099.
         | Crossref | GoogleScholarGoogle Scholar | 1900533PubMed |

[29]  T. D’Ambra, K. Estep, M. Bell, M. Eissenstat, K. Josef, S. Ward, D. Haycock, E. Baizman, F. Casiano, N. Beglin, S. Chippari, J. Grego, R. Kullnig, G. Daley, J. Med. Chem. 1992, 35, 124.
         | Crossref | GoogleScholarGoogle Scholar | 1732519PubMed |

[30]  J. Huffman, D. Dai, B. Martin, D. Compton, Bioorg. Med. Chem. Lett. 1994, 4, 563.
         | Crossref | GoogleScholarGoogle Scholar |

[31]  J. Wiley, D. Compton, D. Dai, J. Lainton, M. Phillips, J. Huffman, B. Martin, J. Pharmacol. Exp. Ther. 1998, 285, 995.
         | 9618400PubMed |

[32]  M. M. Aung, G. Griffin, J. Huffman, M.-J. Wu, C. Keel, B. Yang, V. Showalter, M. Abood, B. Martin, Drug Alcohol Depend. 2000, 60, 133.
         | Crossref | GoogleScholarGoogle Scholar | 10940540PubMed |

[33]  J. Huffman, Curr. Med. Chem. 1999, 6, 705.
         | 10469887PubMed |

[34]  S. Hudson, J. Ramsey, Drug Test. Anal. 2011, 3, 466.
         | Crossref | GoogleScholarGoogle Scholar | 21337724PubMed |

[35]  C. Steup, Untersuchung des Handelsproduktes Spice 2008, THC PHARM GmbH.

[36]  V. Auwärter, S. Dresen, W. Weinmann, M. Muller, M. Putz, N. Ferreiros, J. Mass Spectrom. 2009, 44, 832.
         | Crossref | GoogleScholarGoogle Scholar | 19189348PubMed |

[37]  N. Uchiyama, R. Kikura-Hanajiri, N. Kawahara, Y. Haishima, Y. Goda, Chem. Pharm. Bull. (Tokyo) 2009, 57, 439.
         | Crossref | GoogleScholarGoogle Scholar | 19336947PubMed |

[38]  J. Huffman, R. Mabon, M.-J. Wu, J. Lu, R. Hart, D. Hurst, P. Reggio, J. Wiley, B. Martin, Bioorg. Med. Chem. 2003, 11, 539.
         | Crossref | GoogleScholarGoogle Scholar | 12538019PubMed |

[39]  J. Liddle, J. Huffman, Tetrahedron 2001, 57, 7607.
         | Crossref | GoogleScholarGoogle Scholar |

[40]  J. Huffman, P. Szklennik, A. Almond, K. Bushell, D. Selley, H. He, M. Cassidy, J. Wiley, B. Martin, Bioorg. Med. Chem. Lett. 2005, 15, 4110.
         | Crossref | GoogleScholarGoogle Scholar | 16005223PubMed |

[41]  A. Gandhi, A. Wohlfarth, M. Zhu, S. Pang, M. Castaneto, K. Scheidweiler, M. Heustis, Drug Test. Anal. 2015, 7, 187.
         | Crossref | GoogleScholarGoogle Scholar | 24827428PubMed |

[42]  S. Dresen, N. Ferreiros, M. Putz, F. Westphal, R. Zimmermann, V. Auwärter, J. Mass Spectrom. 2010, 45, 1186.
         | Crossref | GoogleScholarGoogle Scholar | 20857386PubMed |

[43]  S. Kneisel, F. Westphal, P. Bisel, V. Brecht, S. Broecker, V. Auwärter, J. Mass Spectrom. 2012, 47, 195.
         | Crossref | GoogleScholarGoogle Scholar | 22359329PubMed |

[44]  A. Grigoryev, P. Kavanagh, A. Melnik, Drug Test. Anal. 2012, 4, 519.
         | Crossref | GoogleScholarGoogle Scholar | 22102533PubMed |

[45]  S. Banister, S. Wilkinson, M. Longworth, J. Stuart, N. Apetz, K. English, L. Brooker, C. Goebel, D. Hibbs, M. Glass, M. Connor, I. McGregor, M. Kassiou, ACS Chem. Neurosci. 2013, 4, 1081.
         | Crossref | GoogleScholarGoogle Scholar | 23551277PubMed |

[46]  P. Kavanagh, A. Grigoryev, S. Savchuk, I. Mikhura, A. Formanovsky, Drug Test. Anal. 2013, 5, 683.
         | Crossref | GoogleScholarGoogle Scholar | 23315949PubMed |

[47]  N. Langer, R. Lindigkeit, H.-M. Schiebel, L. Ernst, T. Beuerle, Drug Test. Anal. 2014, 6, 59.
         | Crossref | GoogleScholarGoogle Scholar | 23723183PubMed |

[48]  N. Uchiyama, S. Matsuda, M. Kawamura, R. Kikura-Hanajiri, Y. Goda, Forensic Toxicol. 2013, 31, 223.
         | Crossref | GoogleScholarGoogle Scholar |

[49]  S. Banister, J. Stuart, R. Kevin, A. Edington, M. Longworth, S. Wilkinson, C. Beinat, A. S. Buchanan, D. E. Hibbs, M. Glass, M. Connor, I. S. McGregor, M. Kassiou, ACS Chem. Neurosci. 2015, 6, 1445.
         | Crossref | GoogleScholarGoogle Scholar | 25921407PubMed |

[50]  H. Gugelmann, R. Gerona, C. Li, B. Tsutaoka, K. Olson, D. Lung, Clin. Toxicol. 2014, 52, 635.
         | Crossref | GoogleScholarGoogle Scholar |

[51]  S. Banister, M. Moir, J. Stuart, R. Kevin, K. Wood, M. Longworth, S. Wilkinson, C. Beinat, A. Buchanan, M. Glass, M. Connor, I. McGregor, M. Kassiou, ACS Chem. Neurosci. 2015, 6, 1546.
         | Crossref | GoogleScholarGoogle Scholar | 26134475PubMed |

[52]  B. Haschimi, L. Mogler, S. Halter, A. Giorgetti, B. Schwarze, F. Westphal, S. Fischmann, V. Auwärter, Drug Test. Anal. 2019, 11, 1377.
         | Crossref | GoogleScholarGoogle Scholar | 31228224PubMed |

[53]  R. Alam, J. Keating, Drug Test. Anal. 2020, 12, 297.
         | Crossref | GoogleScholarGoogle Scholar | 31854124PubMed |

[54]  A. Carlsson, S. Lindberg, X. Wu, S. Dunne, M. Josefsson, C. Astot, J. Dahlen, Drug Test. Anal. 2016, 8, 1015.
         | Crossref | GoogleScholarGoogle Scholar | 26526273PubMed |

[55]  F. Reniero, P. Lobo, H. Chassaigne, M. Holland, S. Tirendi, K. Kolar, C. Guillou, Report on Characterisation of New Psychoactive Substances (NPS); EUR – Scientific and Technical Research Reports 2014, Publications Office of the European Union.

[56]  C. Guillou, F. Reniero, J. Lobo Vicente, M. Holland, K. Kolar, H. Chassaigne, S. Tirendi, H. Schepers, Curr. Pharm. Biotechnol. 2018, 19, 91.
         | Crossref | GoogleScholarGoogle Scholar | 29792142PubMed |

[57]  R. Silverstein, F. Webster, D. Kiemle, D. Bryce, Spectrometric Identification of Organic Compounds (8th edn) 2014 (Wiley: Hoboken, NJ).

[58]  W. Niessen, D. Falck, in Analyzing Biomolecular Interactions by Mass Spectrometry (Eds J. Kool, W. M. A. Niessen) 2015, pp. 1–54 (Wiley-VCH Verlag GmbH: Weinheim).

[59]  See pp. 351–380 in: O. Zerbe, S. Jurt, Applied NMR Spectroscopy for Chemists and Life Scientists 2014 (Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim).

[60]  See pp. 39–51 in: T. Mitchell, B. Costisella, NMR - From Spectra to Structures 2007 (Springer-Verlag: Berlin).

[61]  See pp. 199–217 in: J. H. Simpson, Organic Structure Determination Using 2-D NMR Spectroscopy: A Problem-Based Approach (2nd edn) 2008 (Academic Press: Burlington, MA).

[62]  See pp. 111–137 in: S. Richards, J. Hollerton, Essential Practical NMR for Organic Chemistry 2011 (Wiley: Chichester).

[63]  EMCDDA (European Monitoring Centre for Drugs and Drug Addiction)http://www.emcdda.europa.eu/topics_en.

[64]  G. Maniara, K. Rajamoorthi, S. Rajan, G. W. S. Stockton, Anal. Chem. 1998, 70, 4921.
         | Crossref | GoogleScholarGoogle Scholar | 21644675PubMed |

[65]  G. Pauli, T. Godecke, B. Jaki, D. Lankin, J. Nat. Prod. 2012, 75, 834.
         | Crossref | GoogleScholarGoogle Scholar | 22482996PubMed |

[66]  P. Hays, J. Forensic Sci. 2005, 50, JFS2005124.
         | Crossref | GoogleScholarGoogle Scholar | 16382828PubMed |

[67]  P. Hays, T. Schoenberger, Anal. Bioanal. Chem. 2018, 28, 7397.

[68]  Y. Monakhova, T. Kuballa, S. Lobell-Behrends, S. Maixner, M. Kohl-Himmelseher, W. Ruge, D. Lachenmeier, Drug Test. Anal. 2013, 5, 400.
         | Crossref | GoogleScholarGoogle Scholar | 22550015PubMed |

[69]  S. Dunne, J. Rosengren-Holmberg, Drug Test. Anal. 2017, 9, 734.
         | Crossref | GoogleScholarGoogle Scholar | 27400773PubMed |

[70]  D. Hibbert, J. Sutton, Aust. J. Forensic Sci. 2017, 49, 605.
         | Crossref | GoogleScholarGoogle Scholar |

[71]  G. Johnston, Aust. J. Forensic Sci. 2017, 49, 626.
         | Crossref | GoogleScholarGoogle Scholar |