Spice/K2 drugs-more than innocent substitutes for marijuana

International Journal of Neuropsychopharmacology

Volumn 17, Issue 3, 2014, Pages 509-525

  Zawilska, Jolanta B ^a   Wojcieszak, Jakub ^a  

^a MEDICAL UNIVERSITY OF LODZ   (Poland)

Author keywords

Abuse; Adverse effects; Spice; Synthetic cannabimimetics; THC

Indexed keywords

2 METHYL 3 (1 NAPHTHOYL) 1 PROPYLINDOLE; 2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 3 (1 NAPHTHOYL) 1 PENTYLINDOLE; AM 694; CANNABINOID; CANNABIS; CP 47 497 C8; CP 47497C 8; DEXANABINOL; JWH 019; JWH 073; JWH 081; JWH 122; JWH 175; JWH 200; JWH 203; JWH 210; JWH 250; JWH 251; JWH 303; JWH 369; RCS 4; UNCLASSIFIED DRUG;

AROMATHERAPY; CANNABIS ADDICTION; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; PREVALENCE; PRIORITY JOURNAL; REVIEW;

CANNABINOIDS; CANNABIS; DESIGNER DRUGS; HUMANS; MARIJUANA ABUSE;

EID: 84897854089     PISSN: 14611457     EISSN: 14695111     Source Type: Journal    
DOI: 10.1017/S1461145713001247     Document Type: Review

References (128)

1. Alhadi S, Tiwari A, Vohra R, Gerona R, Acharya J, Bilello K (2013) High times, low sats: diffuse pulmonary infiltrates associated with chronic synthetic cannabinoid use. J Med Toxicol 9:199-206.
2. Atwood BK, Huffman J, Straiker A, Mackie K (2009) JWH018, common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. Br J harmacol 160:585-593.
3. 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.
4. 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 44:832-837.
5. Barratt MJ, Cakic V, Lenton S (2013) Patterns of synthetic cannabinoid use in Australia. Drug Alcohol Rev 32:141-146.
6. Bebarta VS, Ramirez S, Varney SM (2012) Spice: a new 'legal' herbal mixture abused by young active duty military personnel. Subst Abus 33:191-194.
7. Benford DM, Caplan JP (2011) Psychiatric sequelae of Spice, K2, and synthetic cannabinoid receptor agonists. Psychosomatics 52:295.
8. Berry-Cabán CS, Ee J, Ingram V, Berry CE, Kim EH (2013) Synthetic cannabinoid overdose in a 20-year-old male US solder. Subst Abuse 1:70-72.
9. Bhanushali GK, Jain G, Fatima H, Leisch LJ, Thornley-Brown D (2013) AKI associated with synthetic cannabinoids: a case series. Clin J Am Soc Nephrol 8:523-526.
10. Brents LK, Reichard EE, Zimmerman SM, Moran JH, Fantegrossi WE, Prather PL (2011) Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity. PLoS ONE 6:e21917. doi: 10.1371/journal.pone.0021917.
11. Brents LK, Gallus-Zawada A, Radominska-Pandya A, Vasiljevik T, Prisinzano TE, Fantegrossi WE, Moran JH, Prather PL (2012) Monohydroxylated metabolites of the K2 synthetic cannabinoid JWH-073 retain intermediate to high cannabinoid 1 receptor (CB1R) affinity and exhibit neutral antagonist to partial agonist activity. Biochem Pharmacol 83:952-961.
12. Brents LK, Zimmerman SM, Saffell AR, Prather PL, Fantegrossi WE (2013) Differential drug-drug interactions of the synthetic cannabinoids JWH-018 and JWH-073: implications for drug abuse liability and pain therapy. J Pharmacol Exp Ther 346:350-361.
13. Carroll FI, Lewin AH, Mascarella SW, Seltzman HH, Reddy PA (2012) Designer drugs: a medicinal chemistry perspective. Ann N Y Acad Sci 1248:18-38.
14. CDC (Centers for Disease Control and Prevention) (2013) Acute kidney injury associated with synthetic cannabinoid use-multiple states, 2012. MMWR Morb Mortal Wkly Rep 62:93-98.
15. Chimalakonda KC, Bratton SM, Le VH, Yiew KH, Dineva A, Moran CL, James LP, Moran JH, Radominska-Pandya A (2011a) Conjugation of synthetic cannabinoids JWH-018 and JWH-073, metabolites by human UDP-glucuronosyltransferases. Drug Metab Dispos 39:1967-1976.
16. Chimalakonda KC, Moran CL, Kennedy PD, Endres GW, Uzieblo A, Dobrowolski PJ, Fifer EK, Lapoint J, Nelson LS, Hoffman RS, James LP, Radominska-Pandya A, Moran JH (2011b) Solid-phase extraction and quantitative measurement of omega and omega-1 metabolites of JWH-018 and JWH-073 in human urine. Anal Chem 83:6381-6388.
17. Chimalakonda KC, Seely KA, Bratton SM, Brents LK, Moran CL, Endres GW, James LP, Hollenberg PF, Prather PL, Radominska-Pandya A, Moran JH (2012) Cytochrome P450-mediated oxidative metabolism of abused synthetic cannabinoids found in K2/Spice: identification of novel cannabinoid receptor ligands. Drug Metab Dispos 40:2174-2184.
18. Choi H, Heo S, Choe S, Yang W, Park Y, Kim E, Chung H, Lee J (2013) Simultaneous analysis of synthetic cannabinoids in the materials seized during drug trafficking using GC-MS. Anal Bioanal Chem 405:3937-3944.
19. Cooper ZD, Haney M (2008) Cannabis reinforcement and dependence. Addict Biol 13:188-195.
20. Coulter C, Garnier M, Moore C (2011) Synthetic cannabinoids in oral fluid. J Anal Toxicol 35:424-430.
21. Danovitch I, Gorelick DA (2012) State of art treatments for cannabis dependence. Psychiatr Clin North Am 35:309-326.
22. Dargan PI, Hudson S, Ramsey J, Wood DM (2011) The impact of changes in UK classification of the synthetic cannabinoid receptor agonists in 'Spice'. Int J Drug Policy 22:274-277.
23. Denooz R, Vanheugen JC, Frederich M, de Tullio P, Charlier C (2013) Identification and structural elucidation of four cannabimimetic compounds (RCS-4, AM-2201, JWH-203 and JWH-210) in seized products. J Anal Toxicol 37:56-63.
24. Dresen S, Ferreirós N, Pütz M, Westphal F, Zimmermann R, Auwärter V (2010) Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom 45:1186-1194.
25. Dresen S, Kneisel S, Weinmann W, Zimmermann R, Auwärter V (2011) Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantitation of synthetic cannabinoids of the aminoalkylindole type and methanandamide in serum and its application to forensic samples. J Mass Spectrom 46:163-171.
26. ElSohly MA, Gul W, ElSohly KM, Murphy TP, Madgula VL, Khan SI (2011) Liquid chromatography-tandem mass spectrometry analysis of urine specimens for K2 (JWH-018) metabolites. J Anal Toxicol 35:487-495.
27. EMCDDA (European Monitoring Centre for Drugs and Drug Addiction) (2009) Understanding the 'Spice' phenomenon. Available at: http://www.emcdda.europa.eu/ attachements.cfm/att-80086-EN-Spice%20Thematic%20paper%20-%20final%20version. pdf (accessed 7 October 2013).
28. EMCDDA (European Monitoring Centre for Drugs and Drug Addiction) (2011) Synthetic cannabinoids and 'Spice'. Available at: http://www.emcdda.europa.eu/ publications/drug-profiles/synthetic-cannabinoids (accessed 15 January 2013).
29. Ernst L, Krüger K, Lindigkeit R, Schiebel HM, Beuerle T (2012) Synthetic cannabinoids in 'spice-like' herbal blends: first appearance of JWH-307 and recurrence of JWH-018 on the German market. Forensic Sci Int 222:216-222.
30. Every-Palmer S (2011) Synthetic cannabinoid JWH-018 and psychosis: an explorative study. Drug Alcohol Depend 117:152-157.
31. Faircloth J, Khandheria B, Shum S (2012) Case report: adverse reaction to synthetic marijuana. Am J Addict 21:289-290.
32. Fattore L, Fratta W (2011) Beyond THC: the new generation of cannabinoid designer dugs. Front Behav Neurosci 5:60.
33. Favretto D, Pascali JP, Tagliaro F (2013) New challenges and innovation in forensic toxicology. focus on the 'New Psychoactive Substances'. J Chromatogr A 1287:84-95.
34. Forrester MB, Kleinschmidt K, Schwarz E, Young A (2012) Synthetic cannabinoid and marijuana exposures reported to poison centers. Hum Exp Toxicol 31:1006-1011.
35. Ginsburg BC, Schulze DR, Hruba L, McMahon LR (2012) JWH-018 and JWH-073: δ9-tetrahydrocannabinol-like discriminative stimulus effects in monkeys. J Pharmacol Exp Ther 340:37-45.
36. Gorelick DA, Goodwin RS, Schwilke E, Schwope DM, Darwin WD, Kelly DL, McMahon RP, Liu F, Ortemann-Renon C, Bonnet D, Huestis MA (2013) Tolerance to effects of effects of high-dose oral ?9-tetrahydrocannabinol and plasma cannabinoid concentrations in male daily cannabis smokers. J Anal Toxicol 37:11-16.
37. Gottardo R, Chiarini A, Dal Prà I, Seri C, Rimondo C, Serpelloni G, Armato U, Tagliaro F (2012) Direct screening of herbal blends for new synthetic cannabinoids by MALDI-TOF MS. J Mass Spectrom 47:141-146.
38. Grigoryev A, Savchuk S, Melnik A, Moskaleva N, Dzhurko J, Ershov M, Nosyrev A, Vedenin A, Izotov B, Zabirova I, Rozhanets V (2011) Chromatography-mass spectrometry studies on the metabolism of synthetic cannabinoids JWH-018 and JWH-073, psychoactive components of smoking mixtures. J Chromatogr B Analyt Technol Biomed Life Sci 879:1126-1136.
39. Grigoryev A, Kavanagh P, Melnik A (2012) The detection of the urinary metabolites of 3-[(adamantan-1-yl)carbonyl]-1-pentylindole (AB-001), a novel cannabimimetic, by gas chromatography-mass spectrometry. Drug Test Anal 4:519-524.
40. Grigoryev A, Kavanagh P, Melnik A (2013) The detection of the urinary metabolites of 1-[(5-fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone (AM-694), a high affinity cannabimimetic, by gas chromatography-mass spectrometry. Drug Test Anal 5:110-115.
41. Gronewold A, Skopp G (2011) A preliminary investigation on the distribution of cannabinoids in man. Forensic Sci Int 210(1-3): e7-e11.
42. Grotenhermen F (2003) Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 42:327-360.
43. Grotenhermen F (2007) The toxicology of cannabis and cannabis prohibition. Chem Biodivers 4:1744-1769.
44. Harris CR, Brown A (2013) Synthetic cannabinoid intoxication: a case series and review. J Emerg Med 44:360-366.
45. Hartman RL, Huestis MA (2013) Cannabis effects on driving skills. Clin Chem 59:478-492.
46. Heath TS, Burroughs Z, Thompson AJ, Tecklenburg FW (2012) Acute intoxication caused by a synthetic cannabinoid in two adolescents. J Pediatr Pharmacol Ther 17:177-181.
47. Heltsley R, Shelby MK, Crouch DJ, Black DL, Robert TA, Marshall L, Bender CL, DePriest AZ, Colello MA (2012) Prevalence of synthetic cannabinoids in US athletes: initial findings. J Anal Toxicol 36:588-593.
48. Hermanns-Clausen M, Kneisel S, Szabo B, Auwärter V (2012) Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 108:534-544.
49. Hermanns-Clausen M, Kneisel S, Hutter M, Szabo B, Auwärter V (2013) Acute intoxication by synthetic cannabinoids-four case reports. Drug Test Anal. doi: 10.1002/dta.1483.
50. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161-202.
51. Hoyte CO, Jacob J, Monte AA, Al-Jumaan M, Bronstein AC, Heard KJ (2012) A characterization of synthetic cannabinoid exposures reported to the National Poison Data System in 2010. Ann Emerg Med 60:435-438.
52. Hu X, Primack BA, Barnett TE, Cook RL (2011) College students and use of K2: an emerging drug of abuse in young persons. Subst Abuse Treat Prev Policy 6:16.
53. Hudson S, Ramsey J (2011) The emergence and analysis of synthetic cannabinoids. Drug Test Anal 3:466-478.
54. Hudson S, Ramsey J, King L, Timbers S, Maynard S, Dargan PI, Wood DM (2010) Use of high-resolution accurate mass spectrometry to detect reported and previously unreported cannabinomimetics in 'herbal high' products. J Anal Toxicol 34:252-260.
55. Huffman JW (2009) Cannabinomimetic indoles, pyrroles and indenes: structure-activity relationships and receptor interactions. In: The cannabinoid receptors (Regio PH, ed), Vol. 1, pp49-94. New York: Humana Press.
56. Huffman JW, Dai D, Martin BR (1994) Design, synthesis and pharmacology of cannabinomimetic indoles. Bioorg Med Chem Lett 4:563-566.
57. Huffman JW, Liddle J, Yu S, Aung MM, Abood ME, Wiley JL, Martin BR (1999) 3-(1′,1′-Dimethylbutyl)-1-deoxy-δ8-THC and related compounds: synthesis of selective ligands for the CB2 receptor. Bioorg Med Chem Lett 7:2905-2914.
58. 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.
59. 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 15:4110-4113.
60. Huffman JW, Padgett LW, Isherwood ML, Wiley JL, Martin BR (2006) 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: new high affinity ligands for the cannabinoid CB1 and CB2 receptors. Bioorg Med Chem Lett 16:5432-5435.
61. Hurst D, Loeffler G, McLay R (2011) Psychosis associated with synthetic cannabinoid agonists: a case series. Am J Psychiatry 168:1119.
62. Hutter M, Broecker S, Kneisel S, Auwärter V (2012a) Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in 'herbal mixtures' using LC-MS/MS techniques. J Mass Spectrom 47:54-65.
63. Hutter M, Kneisel S, Auwärter V, Neukamm MA (2012b) Determination of 22 synthetic cannabinoids in human hair by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 903:95-101.
64. Hutter M, Moosmann B, Kneiseel S, Auwärter V (2013) Characterization of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism. J Mass Spectrom 48:885-894.
65. Jinwala FN, Gupta M (2012) Synthetic cannabis and respiratory depression. Child Adolesc Psychopharmacol 22:459-462.
66. Johnson LA, Johnson RL, Portier RB (2013) Current 'Legal highs'. J Emerg Med 44:1108-1115.
67. Kavanagh P, Grigoryev A, Savchuk S, Mikhura I, Formanovsky A (2013) UR-144 in products sold via the internet: identification of related compounds and characterization of pyrolysis products. Drug Test Anal 5:683-692.
68. Klein TW, Cabral GA (2006) Cannabinoid-induced immune suppression and modulation of antigen-presenting cells. J Neuroimmune Pharmacol 1:50-64.
69. Kneisel S, Auwärter V (2012) Analysis of 30 synthetic cannabinoids in serum by liquid chromatography-electrospray ionization tandem mass spectrometry after liquid-liquid extraction. J Mass Spectrom 47:825-835.
70. Langer N, Lindigkeit R, Schiebel HM, Ernst L, Beuerle T (2013) Identification and quantification of synthetic cannabinoids in 'spice-like' herbal mixtures: a snapshot of the German situation in the autumn of 2012. Drug Test Anal. doi: 10.1002/dta.1499.
71. Lapoint J, James LP, Moran CL, Nelson LS, Hoffman RS, Moran JH (2011) Severe toxicity following synthetic cannabinoid ingestion. Clin Toxicol (Phila) 49:760-764.
72. Lewis SE, Paro R, Borriello L, Simon L, Robinson L, Dincer Z, Riedel G, Battista N, Maccarrone M (2012) Long-term use of HU210 adversely affects spermatogenesis in rats by modulating the endocannabinoid system. Int J Androl 35:731-740.
73. Lindigkeit R, Boehme A, Eiserloh I, Luebbecke M, Wiggermann M, Ernst L, Beuerle T (2009) Spice: a never ending story? Forensic Sci Int 191:58-63.
74. Loeffler G, Hurst D, Penn A, Yung K (2012) Spice, bath salts, and the U.S. military: the emergence of synthetic cannabinoid receptor agonists and cathinones in the U.S. Armed Forces. Mil Med 177:1041-1048.
75. Lovinger DM (2008) Presynaptic modulation by endocannabinoids. Handb Exp Pharmacol 184:435-477.
76. Makriyannis A, Deng H (2001) Cannabinomimetic indole derivatives. WO patent 200128557.
77. Malinowska B, Baranowska-Kuczko M, Schlicker E (2012) Triphasic blood pressure responses to cannabinoids: do we understand the mechanism? Br J Pharmacol 165:2073-2088.
78. McQuade D, Hudson S, Dargan PI, Wood DM (2013) First European case of convulsions related to analytically confirmed use of the synthetic cannabinoid receptor agonist AM-2201.Eur J Clin Pharmacol 69:373-376.
79. 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.
80. Mir A, Obafemi A, Young A, Kane C (2011) Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics 128:e1622-e1627.
81. Möller I, Wintermeyer A, Bender K, Jübner M, Thomas A, Krug O, Schänzer W, Thevis M (2011) Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test Anal 3:609-620.
82. Moran CL, Le VH, Chimalakonda KC, Smedley AL, Lackey FD, Owen SN, Kennedy PD, Endres GW, Ciske FL, Kramer JB, Kornilov AM, Bratton LD, Dobrowolski PJ, Wessinger WD, Fantegrossi WE, Prather PL, James LP, Radominska-Pandya A, Moran JH (2011) Quantitative measurement of JWH-018 and JWH-073 metabolites excreted in human urine. Anal Chem 83:4228-4236.
83. Musah RA, Domin MA, Walling MA, Shepard JR (2012) Rapid identification of synthetic cannabinoids in herbal samples via direct analysis in real time mass spectrometry. Rapid Commun Mass Spectrom 26:1109-1114.
84. Musshoff F, Madea B, Kernbach-Wighton G, Bicker W, Kneisel S, Hutter M, Auwärter V (2013) Driving under the influence of synthetic cannabinoids ('Spice'): a case series. Int J Legal Med. doi: 10.1007/s00414-013-0864-1.
85. Müller H, Huttner HB, Köhrmann M, Wielopolski JE, Kornhuber J, Sperling W (2010a) Panic attack after spice abuse in a patient with ADHD. Pharmacopsychiatry 43:152-153.
86. Müller H, Sperling W, Köhrmann M, Huttner HB, Kornhuber J, Maler JM (2010b) The synthetic cannabinoid Spice as a trigger for an acute exacerbation of cannabis induced recurrent psychotic episodes. Schizophr Res 118:309-310.
87. Nacca N, Vatti D, Sullivan R, Sud P, Su M, Maraffa J (2013) The synthetic cannabinoids withdrawal syndrome. J Addict Med 7:296-298.
88. National Conference of State Legislatures (2012). Synthetic Cannabinoids (a.k.a. 'K2'/'Spice') Enactments. Available at: http://www.ncsl.org/issues- research/justice/syntheticcannabinoids-enactments.aspx(accessed 7 October 2013).
89. Office of National Drug Control Policy (2011) Monitoring the future study. Highlights. Available at: http://www.whitehouse.gov/sites/default/files/ ondcp/Blog/2011-monitoring-the-future.pdf (accessed 7 October 2013).
90. Onaivi ES, Carpio O, Ishiguro H, Schanz N, Uhl GR, Benno R (2008) Behavioural effects of CB2 cannabinoid receptor activation and its influence on food and alcohol consumption. Ann N Y Acad Sci 1139:426-433.
91. Pant S, Deshmukh A, Dholaria B, Kaur V, Ramavaram S, Ukor M, Teran GA (2012) Spicy seizure. Am J Med Sci 344:67-68.
92. Patton AL, Chimalakonda KC, Moran CL, McCain KR, Radominska-Pandya A, James LP, Kokes C, Moran JH (2013) K2 toxicity: fatal case of psychiatric complocations following AM2201 exposure. J Forensic Sci. doi: 10.1111/1556-4029.12216.
93. Peglow S, Buchner J, Briscoe G (2012) Synthetic cannabinoid induced psychosis in a previously nonpsychotic patient. Am J Addict 21:287-288.
94. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 62:588-631.
95. Poklis JL, Amira D, Wise LE, Wiebelhaus JM, Haggerty BJ, Poklis A (2012) Detection and disposition of JWH-018 and JWH-073 in mice after exposure to 'Magic Gold' smoke. Forensic Sci Int 220:91-96.
96. Rajasekaran M, Brents LK, Franks LN, Moran JH, Prather PL, (2013) Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors. Toxicol Appl Pharmacol 269:100-108.
97. Rominger A, Cumming P, Xiong G, Koller G, Förster S, Zwergal A, Karamatskos E, Bartenstein P, La Fougère C, Pogarell O (2013) Effects of acute detoxification of the herbal blend 'Spice Gold' on dopamine D2/3 receptor availability: a [18F]fallypride PET study. Eur Neuropsychopharmacol. doi:pii: S0924-977X(13)00048-5.Sativex monograph. Available at: http://www.ukcia.org/ research/ SativexMonograph.pdf (accessed 21 August 2013).
98. Schep LJ, Slaughter RJ, Temple WA (2011) Synthetic cannabinoid use in New Zealand: a brief evaluation of inquiries to the New Zealand National Poisons Centre. N Z Med J 124:99-101.
99. Schneir AB, Baumbacher T (2012) Convulsions associated with the use of a synthetic cannabinoid product. J Med Toxicol 8:62-64.
100. Schneir AB, Cullen J, Ly BT (2011) 'Spice' girls: synthetic cannabinoid intoxication. J Emerg Med 40:296-299.
101. Seely KA, Prather PL, James LP, Moran JH (2011) Marijuana-based drugs: innovative therapeutics or designer drugs of abuse? Mol Interv 11:36-51.
102. Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Morzherin Y, Shafran Y (2012) Identification and analytical properties of new synthetic cannabimimetics bearing 2,2,3,3-tetramethylcyclopropanecarbonyl moiety. Foren Sci Int 226:62-73.
103. 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 278:989-999.
104. Simmons J, Cookman L, Kang C, Skinner C (2011) Three cases of 'spice' exposure. Clin Toxicol (Phila) 49:431-433.
105. Simolka K, Lindigkeit R, Schiebel HM, Papke U, Ernst L, Beuerle T (2012) Analysis of synthetic cannabinoids in 'spice-like' herbal highs: snapshot of the German market in summer 2011. Anal Bioanal Chem 404:157-171.
106. Sobolevsky T, Prasolov I, Rodchenkov G (2010) Detection of JWH-018 metabolites in smoking mixture post-administration urine. Forensic Sci Int 200:141-147.
107. Teske J, Weller JP, Fieguth A, Rothämel T, Schulz Y, Tröger HD (2010) Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatographytandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878:2659-2663.
108. Thomas S, Bliss S, Malik M (2012) Suicidal ideation and self-harm following K2 use. J Okla State Med Ossoc 105:430-433.
109. Tung CK, Chiang TP, Lam M (2012) Acute mental disturbance caused by synthetic cannabinoid: a potential emerging substance of abuse in Hong Kong. East Asian Arch Psychiatry 22:31-33.
110. Uchiyama N, Kikura-Hanajiri R, Ogata J, Goda Y (2010) Chemical analysis of synthetic cannabinoids as designer drugs in herbal products. Forensic Sci Int 198:1-8.
111. Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2011a) Identification and quantitative analyses of two cannabinomimetic phenacetylindoles, JWH-251 and JHW-250, and four cannabinomimetic naphtoylindoles, JWH-081, JWH-015, JWH-200 and JW-073, as designer drugs in illegal products. Forensic Toxic 29:25-37.
112. Uchiyama N, Kikura-Hanajiri R, Goda Y (2011b) Identification of a novel cannabinomimetic phenylacetylindole, cannabipiperididiethanone, as a designer drug in a herbal product and its affinity for CB1 and CB2 receptors. Chem Pharm Bull 59:1203-1205.
113. Uchiyama N, Kikura-Hanajiri R, Matsumoto N, Huang Z-L, Goda Y, Urade Y (2012) Effects of synthetic cannabinoids on electroencephalogram power spectra in rats. Forensic Sci Int 215:179-183.
114. Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2013) URB-754: a new class of designer drug and 12 synthetic cannabinoids detected in illegal products. Forensic Sci Int 227:21-32.
115. UNODC (United Nations Office on Drugs and Crime) (2010). Synthetic cannabinoids in herbal products. Available at: http://www.unodc.org/documents/ scientific/Synthetic-Cannabinoids.pdf (accessed 24 April 2013).
116. Vandrey R, Dunn KE, Fry JA, Girling ER (2012) A survey study to characterize use of Spice products (synthetic cannabinoids). Drug Alcohol Depend 120:238-241.
117. Vann RE, Warner JA, Bushell K, Huffman JW, Martin BR, Wiley JL (2009) Discriminative stimulus properties of δ9-tetrahydrocannabinol (THC) in C57Bl/6J mice. Eur J Pharmacol 615:102-107.
118. Vardakou I, Pistos C, Spiliopoulou C (2010) Spice drugs as a new trend: mode of action, identification and legislation. Toxicol Lett 197:157-162.
119. Vearrier D, Osterhoudt KC (2010) A teenager with agitation: higher than she should have climbed. Pediatr Emerg Care 26:462-465.
120. Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I (2007) Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci 80:1415-1419.
121. Wiebelhaus JM, Poklis JL, Poklis A, Vann RE, Lichtman AH, Wise LE (2012) Inhalation exposure to smoke from synthetic "marijuana" produces potent cannabimimetic effects in mice. Drug Alcohol Depend 126:316-323.
122. Winstock AR, Barratt MJ (2013) Synthetic cannabis: a comparison of patterns of use and effect profile with natural cannabis in a large global sample. Drug Alcohol Depend 131:106-111.
123. Wintermeyer A, Möller I, Thevis M, Jübner M, Beike J, Rothschild MA, Bender K (2010) In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. Anal Bioanal Chem 398:2141-2153.
124. Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, Yang HJ, Bi GH, Li J, Gardner EL (2011) Brain cannabinoid CB2 receptors modulate cocaine's actions in mice. Nat Neurosci 14:1160-1166.
125. Young AC, Schwarz E, Medina G, Obafemi A, Feng SY, Kane C, Kleinschmidt K (2012) Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation. Am J Emerg Med 30:1320.e5-e7.
126. Zawilska JB (2011) 'Legal highs'-new players in the old drama. Curr Drug Abuse Rev 4:122-130.
127. Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K (2009) Withdrawal phenomena and dependence syndrome after the consumption of 'spice gold'. Dtsch Arztebl Int 106:464-467.
128. Zuba D, Byrska B, Maciow M (2011) Comparison of 'herbal highs' composition. Anal Bioanal Chem 400:119-126.