The emergence and analysis of synthetic cannabinoids.

In late 2008, several synthetic cannabinoids were detected in herbal smoking mixtures. Typical of these products were 'Spice Gold', 'Spice Silver' and 'Yucatan Fire', but many other products have since appeared. The analytes detected, such as JWH-018 and CP47,497 are experimental compounds, some of which were never designed for human use. Both scientific and anecdotal evidence suggest that these compounds are more potent than traditional cannabis and are being widely used. As a result, authorities around the world are now beginning to control them by either naming individual compounds or using generic legislation. This, however, is easier said than done as the synthetic cannabinoids detected are constantly changing in attempts by manufacturers to evade legislation. This paper includes background information in the style of a brief monograph, as an aid to rapidly understanding the pharmacological aspects of these compounds in the forensic context, and then presents a comprehensive set of data, obtained from analysis of purchased products by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

[1]  R. Pertwee,et al.  Pharmacological actions of cannabinoids. , 2005, Handbook of experimental pharmacology.

[2]  J. Huffman.  Cannabimimetic Indoles, Pyrroles, and Indenes: Structure–Activity Relationships and Receptor Interactions , 2009 .

[3]  J. Ramsey,et al.  The impact of changes in UK classification of the synthetic cannabinoid receptor agonists in 'Spice'. , 2011, The International journal on drug policy.

[4]  Y. Goda,et al.  Identification of a cannabimimetic indole as a designer drug in a herbal product , 2009, Forensic Toxicology.

[5]  R. Spanagel,et al.  Withdrawal phenomena and dependence syndrome after the consumption of "spice gold". , 2009, Deutsches Arzteblatt international.

[6]  I. Vardakou,et al.  Spice drugs as a new trend: mode of action, identification and legislation. , 2010, Toxicology letters.

[7]  Grigory Rodchenkov,et al.  Detection of JWH-018 metabolites in smoking mixture post-administration urine. , 2010, Forensic science international.

[8]  Y. Haishima,et al.  Identification of a cannabinoid analog as a new type of designer drug in a herbal product. , 2009, Chemical & pharmaceutical bulletin.

[9]  Marion Kee,et al.  Analysis , 2004, Machine Translation.

[10]  G. Hynd,et al.  Structure-activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB(1) and CB(2) receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB(2) receptor agonists. , 2005, Bioorganic & medicinal chemistry.

[11]  Ming-Jung Wu,et al.  Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding. , 2000, Drug and alcohol dependence.

[12]  J. Ramsey,et al.  Use of high-resolution accurate mass spectrometry to detect reported and previously unreported cannabinomimetics in "herbal high" products. , 2010, Journal of analytical toxicology.

[13]  A. Brown.  Novel cannabinoid receptors , 2007, British journal of pharmacology.

[14]  Wayne Hall,et al.  Adverse effects of cannabis , 1998, The Lancet.

[15]  T. Bonner,et al.  Structure of a cannabinoid receptor and functional expression of the cloned cDNA , 1990, Nature.

[16]  D. R. Compton,et al.  Structure-activity relationships of indole- and pyrrole-derived cannabinoids. , 1998, The Journal of pharmacology and experimental therapeutics.

[17]  M. Thevis,et al.  Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. , 2011, Drug testing and analysis.

[18]  M. Herkenham,et al.  International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors , 2002, Pharmacological Reviews.

[19]  M. Thevis,et al.  In vitro phase I metabolism of the synthetic cannabimimetic JWH-018 , 2010, Analytical and bioanalytical chemistry.

[20]  R. Cole,et al.  Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS , 2006, Analytical and bioanalytical chemistry.

[21]  Y. Goda,et al.  Chemical analysis of synthetic cannabinoids as designer drugs in herbal products. , 2010, Forensic science international.

[22]  N. Ferreirós,et al.  'Spice' and other herbal blends: harmless incense or cannabinoid designer drugs? , 2009, Journal of mass spectrometry : JMS.

[23]  K. Rice,et al.  Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. , 1993, The Journal of pharmacology and experimental therapeutics.

[24]  Ming-Jung Wu,et al.  3-Indolyl-1-naphthylmethanes: new cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB(1) cannabinoid receptor. , 2003, Bioorganic & medicinal chemistry.

[25]  S. Munro,et al.  Molecular characterization of a peripheral receptor for cannabinoids , 1993, Nature.

[26]  A. Howlett,et al.  Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. , 1984, Molecular pharmacology.

[27]  M. Johnson,et al.  Pharmacological profile of a series of bicyclic cannabinoid analogs: classification as cannabimimetic agents. , 1992, The Journal of pharmacology and experimental therapeutics.

[28]  R. Lindigkeit,et al.  Spice: a never ending story? , 2009, Forensic science international.

[29]  C. Ashton.  Adverse effects of cannabis and cannabinoids. , 1999, British journal of anaesthesia.