Spicing things up: Synthetic cannabinoids

Psychopharmacology

Volumn 228, Issue 4, 2013, Pages 525-540

  Spaderna, Max ^a   Addy, Peter H ^a,b,c   D'Souza, Deepak Cyril ^a,b,c  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VA CONNECTICUT HEALTHCARE SYSTEM   (United States)

^c Abraham Ribicoff Research Facilities   (United States)

Author keywords

Cannabinoids; Cannabis; CB1; K2; Spice; Synthetic cannabinoids; THC

Indexed keywords

ACTIVATED CARBON; ANTIEMETIC AGENT; BENZODIAZEPINE DERIVATIVE; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID DERIVATIVE; CANNABINOID RECEPTOR AGONIST; CANNABIS; DIPHENHYDRAMINE; DRONABINOL; HALOPERIDOL; ILLICIT DRUG; LORAZEPAM; NEUROLEPTIC AGENT; PSYCHOTROPIC AGENT; SPICE (DRUG); UNCLASSIFIED DRUG;

AGITATION; ANXIETY DISORDER; ATTENTION DISTURBANCE; BEHAVIOR DISORDER; BINDING AFFINITY; CANNABIS ADDICTION; CARDIOVASCULAR DISEASE; CATATONIA; CHEMICAL COMPOSITION; COGNITIVE DEFECT; DISEASE ASSOCIATION; DRUG CONTROL; DRUG DEPENDENCE; DYSPHORIA; EMERGENCY CARE; GASTROINTESTINAL SYMPTOM; GOVERNMENT REGULATION; HANGOVER; HOSPITAL CARE; HUMAN; INTOXICATION; LABORATORY TEST; LAW ENFORCEMENT; MEMORY DISORDER; MENTAL DISEASE; NEUROLOGIC DISEASE; PANIC; PERCEPTION; PHYSICAL TOLERANCE; POISON CENTER; PRIORITY JOURNAL; PSYCHOSIS; RECEPTOR BINDING; REVIEW; SELF REPORT; TACHYCARDIA; THOUGHT DISORDER; TOXICOLOGY; URINALYSIS; VOMITING;

ANIMALS; CANNABINOIDS; DESIGNER DRUGS; HUMANS; LEGISLATION, DRUG; STREET DRUGS; SUBSTANCE ABUSE DETECTION; SUBSTANCE-RELATED DISORDERS;

EID: 84881225471     PISSN: 00333158     EISSN: 14322072     Source Type: Journal    
DOI: 10.1007/s00213-013-3188-4     Document Type: Review

References (181)

1. AAPCC (2011) Synthetic marijuana data. http://www.aapcc.org/alerts/ synthetic-marijuana/. Accessed 13 May 2012
2. Addy P (2007) Facilitating transpersonal experiences with dextromethorphan: potential, cautions, and caveats. J Transpers Psychol 39:1-22
3. 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
4. Ashton JC (2012) Synthetic cannabinoids as drugs of abuse. Curr Drug Abuse Rev 5:158-168
5. Atwood BK, Huffman J, Straiker A, Mackie K (2010) JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. Br J Pharmacol 160:585-593
6. Atwood BK, Lee D, Straiker A, Widlanski TS, Mackie K (2011) CP47,497-C8 and JWH073, commonly found in 'Spice' herbal blends, are potent and efficacious CB(1) cannabinoid receptor agonists. Eur J Pharmacol 659:139-145
7. 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 CB(1) and CB(2) receptor binding. Drug Alcohol Depend 60:133-140
8. Auwarter V, Dresen S, Weinmann W, Muller M, Putz M, Ferreiros N (2009) 'Spice' and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom 44:832-837
9. Banerji S, Deutsch CM, Bronstein AC (2010) SPICE ain't so nice http://rmpdc.org/Portals/23/Spice%20Poster%20Final%202010.pdf. Accessed 20 April 2012
10. Barratt MJ, Cakic V, Lenton S (2013) Patterns of synthetic cannabinoid use in Australia. Drug Alcohol Rev 32:141-146
11. 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
12. Benford DM, Caplan JP (2011) Psychiatric sequelae of Spice, K2, and synthetic cannabinoid receptor agonists. Psychosomatics 52:295
13. Benji (2010) More than meets the eye http://www.erowid.org/experiences/ exp.php?ID=84194. Accessed 1 May 2012
14. Berry-Caban CS, Ee J, Ingram V, Berry CE, Kim EH (2013) Synthetic cannabinoid overdose in a 20-year-old male US soldier. Subst Abus 34:70-72
15. Berry-Caban CS, Kleinschmidt PE, Rao DS, Jenkins J (2012) Synthetic cannabinoid and cathinone use among US soldiers. US Army Medical Department journal: 19-24
16. 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
17. Bhattacharyya S, Fusar-Poli P, Borgwardt S, Martin-Santos R, Nosarti C, O'Carroll C, Allen P, Seal ML, Fletcher PC, Crippa JA, Giampietro V, Mechelli A, Atakan Z, McGuire P (2009) Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. Arch Gen Psychiatry 66:442-451
18. Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O' Carroll CM, Seal M, Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, McGuire PK (2010) Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35:764-774
19. Bhatty S, Wu W (2013) Organic and synthetic cannabinoid use in adolescents. Pediatr Ann 42:31-35
20. Borgwardt SJ, Allen P, Bhattacharyya S, Fusar-Poli P, Crippa JA, Seal ML, Fraccaro V, Atakan Z, Martin-Santos R, O'Carroll C, Rubia K, McGuire PK (2008) Neural basis of Delta-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition. Biol Psychiatry 64:966-973
21. Boyle J (2011) 'Spice' manufacturers change formula, sell drug again http://www.middletownjournal.com/news/middletown-news/spice-manufacturers- change-formula-sell-drug-again-1306082.html Middletown Journal. Accessed 28 April 2012
22. 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
23. 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
24. Brown K (2011) New Zealand bans synthetic cannabinoids. BMJ 343:d5395
25. Bryner J (2010) Fake weed, real drug: K2 causing hallucinations in teens http://www.livescience.com/6149-fake-weed-real-drug-k2-causing-hallucinations- teens.html. Live Science Volume. Accessed 20 April 2012
26. Canning JC, Ruha AM, Pierce R, Torrey M, Reinhart SJ (2010) Severe GI distress after smoking JWH018. Clin Toxicol 48:618
27. Castellanos D, Singh S, Thornton G, Avila M, Moreno A (2011) Synthetic cannabinoid use: a case series of adolescents. J Adolesc Heal 49:347-349
28. Castellanos D, Thornton G (2012) Synthetic cannabinoid use: recognition and management. J Psychiatr Pract 18:86-93
29. CDC (2013) Acute kidney injury asociated with synthetic cannabinoid use - multiple states, 2012. MMWR Morb Mortal Wkly Rep 62:93-98
30. Chainsaw (2009) Like cold lemonade. http://www.erowid.org/experiences/ exp.php?ID=79040. Accessed 1 May 2012
31. 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
32. 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
33. 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
34. CitrusBlank1928 (2009) Spice it right. http://www.erowid.org/experiences/ exp.php?ID=80091. Accessed 1 May 2012
35. coffeeman64 (2008) Nearly 100 percent comparable. http://www.erowid.org/ experiences/exp.php?ID=66428. Accessed 1 May 2012
36. Code of Federal Regulations (2011) Schedule I. 21 CFR 1308(h)
37. Cohen J, Morrison S, Greenberg J, Saidinejad M (2012) Clinical presentation of intoxication due to synthetic cannabinoids. Pediatrics 129:e1064-e1067
38. Commando420 (2009) Simply amazing. http://www.erowid.org/experiences/exp. php?ID=78604. Accessed 1 May 2012
39. Coyle JR, Presti DE, Baggott MJ (2012) Quantitative analysis of narrative reports of psychedelic drugs. arXiv preprint arXiv:12060312.
40. D'Ambra TE, Estep KG, Bell MR, Eissenstat MA, Josef KA, Ward SJ, Haycock DA, Baizman ER, Casiano FM, Beglin NC et al (1992) Conformationally restrained analogues of pravadoline: nanomolar potent, enantioselective, (aminoalkyl)indole agonists of the cannabinoid receptor. J Med Chem 35:124-135
41. Dan (2009) Unnatural and unpleasant. http://www.erowid.org/experiences/ exp.php?ID=79039. Accessed 1 May 2012
42. 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
43. DEA (2011) Synthetic cannabinoids and synthetic cathinones reported in NFLIS, 2009-2010. In: Agency DE (ed). National Forensic Laboratory Information System
44. DEA (2012) DEA NEWS: nationwide synthetic drug takedown, US DOJ DEA http://www.justice.gov/usao/id/news/images/dearelease07262012.pdf. Accessed 1 October 2012
45. Deluca P, Schifano F, Davey Z, Corazza O, di Furia L, Farre M, Flesland L, Mannonen M, Majava A, Valentina M, Pagani S, Peltoniemi T, Scherbaum N, Siemann H, Skutle A, Torrens M, Pezzolesi C, van der Kreeft P (2009) Psychonaut Web Mapping Research Group: spice report. In: Group PWMR (ed) Institute of Psychiatry. King's College London, London
46. Devane WA, Dysarz FA 3rd, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605-613
47. Donnelly MT (2010) Health advisory: K2 synthetic marijuana use among teenagers and young adults in Missouri. In: Services MDoHaS (ed)
48. Door - King (2009) Not pot. http://www.erowid.org/experiences/exp.php?ID= 77867. Accessed 1 May 2012
49. Dr - Toata - Phikal (2013) Marijuana for K2 withdrawal. http://www.erowid.org/experiences/exp.php?ID=94940. Accessed 1 April 2012
50. Dreaded - Joe (2010) The most amazing sense in the world! http://www.erowid.org/experiences/exp.php?ID=78012. Accessed 1 May 2012
51. Dresen S, Ferreiros N, Putz M, Westphal F, Zimmermann R, Auwarter V (2010) Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom 45:1186-1194
52. Dresen S, Kneisel S, Weinmann W, Zimmermann R, Auwarter 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
53. Ellsworth H, Stellpflug S (2011) Déjà vu, another designer drug: synthetic cannabinoids - Toxicology Section Newsletter http://wsol.acep.org/Content.aspx?id=77201. Accessed 20 April 2012
54. Elsohly MA, Slade D (2005) Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 78:539-548
55. Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, Stone JM, Reichenberg A, Brenneisen R, Holt D, Feilding A, Walker L, Murray RM, Kapur S (2013) Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol 27:19-27
56. Ernst L, Kruger 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
57. Erowid (2013) Spice product legal status. http://www.erowid.org/ chemicals/spice-product/spice-product-law.shtml. Accessed 1 April 2012
58. European Monitoring Centre for Drugs and Drug Addiction E (2002) Report on the risk assessment of GHB in the framework of the joint action on new synthetic drugs. Office for Official Publications of the European Communities, Luxembourg
59. European Monitoring Centre for Drugs and Drug Addiction E (2005) Europol-EMCDDA Active Monitoring Report on a new psychoactive substance: 1-(3-chlorophenyl)piperazine (mCPP). Office for Official Publications of the European Communities, Lisbon
60. European Monitoring Centre for Drugs and Drug Addiction E (2006) Thematic paper - hallucinogenic mushrooms: an emerging trend case study. Office for Official Publications of the European Communities, Lisbon
61. European Monitoring Centre for Drugs and Drug Addiction E (2009) Thematic paper - understanding the 'Spice' phenomenon. Office for Official Publications of the European Communities, Luxembourg
62. Every-Palmer S (2010) Warning: legal synthetic cannabinoid-receptor agonists such as JWH-018 may precipitate psychosis in vulnerable individuals. Addiction 105:1859-1860
63. Every-Palmer S (2011) Synthetic cannabinoid JWH-018 and psychosis: an explorative study. Drug Alcohol Depend 117:152-157
64. Fattore L, Fratta W (2011) Beyond THC: the new generation of cannabinoid designer drugs. Front Behav Neurosci 5:60
65. Flashback (2007) Basically cannabis, minus the fun. http://www.erowid. org/experiences/exp.php?ID=50226. Accessed 1 May 2012
66. Forrester MB, Kleinschmidt K, Schwarz E, Young A (2011) Synthetic cannabinoid exposures reported to Texas poison centers. J Addict Dis 30:351-358
67. Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A, Borgwardt S, Martin-Santos R, Seal ML, O'Carrol C, Atakan Z, Zuardi AW, McGuire P (2010) Modulation of effective connectivity during emotional processing by delta 9-tetrahydrocannabinol and cannabidiol. Int J Neuropsychopharmacol 13:421-432
68. Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, Seal M, Surguladze SA, O'Carrol C, Atakan Z, Zuardi AW, McGuire PK (2009) Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry 66:95-105
69. Gay M (2010) Synthetic marijuana spurs state ban. The New York Times http://wwwnytimescom/2010/07/11/us/11k2html?-r=0. Accessed 20 April 2012
70. Gifford AN, Bruneus M, Lin S, Goutopoulos A, Makriyannis A, Volkow ND, Gatley SJ (1999) Potentiation of the action of anandamide on hippocampal slices by the fatty acid amide hydrolase inhibitor, palmitylsulphonyl fluoride (AM 374). Eur J Pharmacol 383:9-14
71. Ginsburg BC, McMahon LR, Sanchez JJ, Javors MA (2012) Purity of synthetic cannabinoids sold online for recreational use. J Anal Toxicol 36:66-68
72. Gould J (2010) Legal high becomes 'horrible dream.' Army Times http://wwwarmytimescom/news/2010/10/SATURDAYarmy-spice-became-horrible-dream- roudebush-100210w/. Accessed 20 April 2012
73. Gunderson EW, Haughey HM, Ait-Daoud N, Joshi AS, Hart CL (2012) "Spice" and "K2" herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans. Am J Addict 21:320-326
74. Harris CR, Brown A (2013) Synthetic cannabinoid intoxication: a case series and review. J Emerg Med 44:360-366
75. 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
76. Hermanns-Clausen M, Kneisel S, Szabo B, Auwarter V (2013) Acute toxicity due to the confirmed consumption of synthetic cannabinoids: clinical and laboratory findings. Addiction 108:534-544
77. Hippieman420 (2009) Just like the real thing. http://www.erowid.org/ experiences/exp.php?ID=76286. Accessed 1 May 2012
78. 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
79. 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
80. Hu X, Primack BA, Barnett TE, Cook RL (2011) College students and use of K2: an emerging drug of abuse in young persons. Substance Abuse Treatment, Prevention, and Policy 6: 16
81. Hudson S, Ramsey J (2011) The emergence and analysis of synthetic cannabinoids. Drug Test Anal 3:466-478
82. Huffman JW, Padgett LW (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 12:1395-1411
83. Huffman JW, Szklennik PV, Almond A, Bushell K, Selley DE, He H, Cassidy MP, Wiley JL, Martin BR (2005a) 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles. Bioorg Med Chem Lett 15:4110-4113
84. Huffman JW, Zengin G, Wu MJ, Lu J, Hynd G, Bushell K, Thompson AL, Bushell S, Tartal C, Hurst DP, Reggio PH, Selley DE, Cassidy MP, Wiley JL, Martin BR (2005b) 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. Bioorg Med Chem 13:89-112
85. Hurst D, Loeffler G, McLay R (2011) Psychosis associated with synthetic cannabinoid agonists: a case series. Am J Psychiatry 168:1119
86. Jack A (2009) The story of Spice. The Financial Times Online http://wwwftcom/cms/s/0/1721e2da-f8a0-11dd-aae8-000077b07658html#axzz2VDpo0fdr. Accessed 20 April 2012
87. Johnson LA, Johnson RL, Alfonzo C (2011) Spice: a legal marijuana equivalent. Mil Med 176:718-720
88. Johnston LD, O'Malley PM, Bachman JG, Schulenberg JED, 2011). Marijuana use continues to rise among U.S. teens, while alcohol use hits historic lows. University of Michigan News Service: Ann Arbor, MI. Available at http://www.monitoringthefuture.org. Accessed 29 April 2012
89. Jouvenal J (2011) 'Spice' makers change recipes to sidestep bans. USA Today http://usatoday30usatodaycom/USCP/PNI/NEWS/2011-12-30-PNI1230wir-Spice-ST- Uhtm. Accessed 20 April 2012
90. JSB2010 (2011) It needed to be respected but I didn't. http://www.erowid.org/experiences/exp.php?ID=92368. Accessed 1 May 2012
91. Kikura-Hanajiri R, Uchiyama N, Goda Y (2011) Survey of current trends in the abuse of psychotropic substances and plants in Japan. Leg Med (Tokyo) 13:109-115
92. Kneisel S, Westphal F, Bisel P, Brecht V, Broecker S, Auwarter V (2012) Identification and structural characterization of the synthetic cannabinoid 3-(1-adamantoyl)-1-pentylindole as an additive in 'herbal incense'. J Mass Spectrom 47:195-200
93. Kratoman (2009) Really high for a really long time. http://www.erowid. org/experiences/exp.php?ID=79674. Accessed 1 May 2012
94. 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
95. Leonhart M (2012) Schedules of controlled substances: placement of five synthetic cannabinoids into Schedule I. In: Justice Do (ed)
96. Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkotter J, Hellmich M, Koethe D (2012) Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2:e94
97. Leweke FM, Schneider U, Radwan M, Schmidt E, Emrich HM (2000) Different effects of nabilone and cannabidiol on binocular depth inversion in man. Pharmacol Biochem Behav 66:175-181
98. 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
99. 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
100. Loschner A, Cihla A, Falali F, Ghamande S (2011) Diffuse alveolar hemorrhage: add "greenhouse effect" to the growing list. Chest 140:149A
101. marianne (2008) A pleasant cannabis alternative. http://www.erowid.org/ experiences/exp.php?ID=67062. Accessed 1 May 2012
102. Marriott KS, Huffman JW (2008) Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor. Curr Top Med Chem 8:187-204
103. McGuinness TM, Newell D (2012) Risky recreation: synthetic cannabinoids have dangerous effects. J Psychosoc Nurs Ment Heal Serv 50:16-18
104. 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
105. 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
106. Mir A, Obafemi A, Young A, Kane C (2011) Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics 128:e1622-e1627
107. mixmaster (2009) Nearly identical to MJ but longer lasting. http://www.erowid.org/experiences/exp.php?ID=77872. Accessed 1 May 2012
108. Modern - Famicom (2009) The seller of religions, and hell. http://www.erowid.org/experiences/exp.php?ID=80051. Accessed 1 May 2012
109. Modern - Famicom (2009) Spicehot. http://www.erowid.org/experiences/exp. php?ID=80223. Accessed 1 May 2012
110. Montauk (2010) Anti-escapism. http://www.erowid.org/experiences/exp.php? ID=80755. Accessed 1 May 2012
111. 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
112. Morgan CJ, Curran HV (2008) Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiatry 192:306-307
113. Morgan CJ, Freeman TP, Schafer GL, Curran HV (2010) Cannabidiol attenuates the appetitive effects of delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology 35:1879-1885
114. Muller H, Huttner HB, Kohrmann M, Wielopolski JE, Kornhuber J, Sperling W (2010a) Panic attack after spice abuse in a patient with ADHD. Pharmacopsychiatry 43:152-153
115. Muller H, Sperling W, Kohrmann 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
116. 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: RCM 26:1109-1114
117. Musshoff F, Madea B, Kernbach-Wighton G, Bicker W, Kneisel S, Hutter M, Auwarter V (2013) Driving under the influence of synthetic cannabinoids ("Spice"): a case series. Int J Legal Med. doi: 10.1007/s00414-013- 0864-1
118. NIDA (2012) Drug facts: spice (synthetic marijuana). http://www. drugabuse.gov/publications/drugfacts/spice-synthetic-marijuana. Accessed 1 April 2012
119. Nostalgia (2010) Only physically drunk. http://www.erowid.org/ experiences/exp.php?ID=84664. Accessed 1 May 2012
120. Ogata J, Uchiyama N, Kikura-Hanajiri R, Goda Y (2013) DNA sequence analyses of blended herbal products including synthetic cannabinoids as designer drugs. Forensic Sci Int 227:33-41
121. Oluwabusi OO, Lobach L, Akhtar U, Youngman B, Ambrosini PJ (2012) Synthetic cannabinoid-induced psychosis: two adolescent cases. J Child Adolesc Psychopharmacol 22:393-395
122. Pant S, Deshmukh A, Dholaria B, Kaur V, Ramavaram S, Ukor M, Teran GA (2012) Spicy seizure. Am J Med Sci 344:67-68
123. Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 153:199-215
124. Piggee C (2009) Investigating a not-so-natural high. Anal Chem 81:3205-3207
125. Potty (2009) Very bad for my lungs. http://www.erowid.org/experiences/ exp.php?ID=79567. Accessed 1 May 2012
126. Psychoyos D, Vinod KY (2013) Marijuana, Spice 'herbal high', and early neural development: implications for rescheduling and legalization. Drug Test Anal 5:27-45
127. Radhakrishnan R, Addy PH, Sewell RA, Skosnik PD, Ranganthan M, D'Souza DC (2012) Cannabis, cannabinoids, and the association with psychosis. In: Madras B, Kuhar MJ (eds) The effects of drug abuse on the human nervous system. Neuroscience-Net, LLC
128. Resolute (2009) Not what I expected. http://www.erowid.org/experiences/ exp.php?ID=79497. Accessed 1May 2012
129. rev.MRC (2009) My cannabinoid receptors are tingling. http://www.erowid.org/experiences/exp.php?ID=76971. Accessed 1 May 2012
130. Riddirk (2008) Differing body states http://www.erowid.org/experiences/ exp.php?ID=67444. Accessed 1 May 2012
131. Riley (2012) Withdrawal from herbal incense. http://www.erowid.org/ experiences/exp.php?ID=96302. Accessed 15 June 2012
132. Rodgman C, Kinzie E, Leimbach E (2011) Bad Mojo: use of the new marijuana substitute leads to more and more ED visits for acute psychosis. Am J Emerg Med 29:232
133. Rominger A, Cumming P, Xiong G, Koller G, Forster S, Zwergal A, Karamatskos E, Bartenstein P, La Fougere C, Pogarell O (2013) Effects of acute detoxification of the herbal blend 'Spice Gold' on dopamine D receptor availability: a [F]fallypride PET study. Eur Neuropsychopharmacol. doi: 10.1016/j.euroneuro.2013.01.009
134. Rose J (2012) Fake pot is a real problem for regulators. National Public Radio News (http://m.npr.org/news/U.S./156615024). Accessed 1 October 2012
135. Rosenbaum CD, Carreiro SP, Babu KM (2012) Here today, gone tomorrow.and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. J Med Toxicol 8:15-32
136. S Carter (2010) Possible addiction. http://www.erowid.org/experiences/ exp.php?ID=91493. Accessed 1 May 2012
137. Sage2240 (2009) Similar to but different than cannabis. http://www.erowid.org/experiences/exp.php?ID=76383. Accessed 1 May 2012
138. Scalzo A (2010) K2 synthetic marijuana use among teenagers - Missouri, 2010. The Epidemic Information Exchange. http://wwwiowagov/odcp/docs/Spice/ K2Marijuanapdf. Accessed 20 April 2012
139. Schatz AR, Lee M, Condie RB, Pulaski JT, Kaminski NE (1997) Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. Toxicol Appl Pharmacol 142:278-287
140. Schifano F, Ricciardi A, Corazza O, Deluca P, Davey Z, Rafanelli C (2010) New drugs of abuse on the Web: the role of the Psychonaut Web Mapping Project. Riv Psichiatr 45:88-93
141. Schifiano F, Corazza O, Deluca P, Davey Z, Lucia DF, Farre M, Flesland L, Mannonen M, Pagani S, Peltoniemi T, Pezzolesi C, Scherbaum N, Siemann H, Skutle A, Torrens M, Van Der Kreeft P (2009) Psychoactive drug mystical incense? Overview of the online available information on Spice products. Int J Cult Ment Health 2:137-144
142. Schneir AB, Baumbacher T (2012) Convulsions associated with the use of a synthetic cannabinoid product. J Med Toxicol 8:62-64
143. Schneir AB, Cullen J, Ly BT (2011) "Spice" girls: synthetic cannabinoid intoxication. J Emerg Med 40:296-299
144. Seely KA, Lapoint J, Moran JH, Fattore L (2012) Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry 39:234-243
145. Seely KA, Prather PL, James LP, Moran JH (2011) Marijuana-based drugs: innovative therapeutics or designer drugs of abuse? Mol Interv 11:36-51
146. Sewell RA, Skosnik PD, Garcia-Sosa I, Ranganathan M, D'Souza DC (2010) Behavioral, cognitive and psychophysiological effects of cannabinoids: relevance to psychosis and schizophrenia. Rev Bras Psiquiatr 32(1):S15-S30
147. Shakes (2008) Can't believe this is legal. http://www.erowid.org/ experiences/exp.php?ID=74660. Accessed 1 May 2012
148. Shanks KG, Dahn T, Terrell AR (2012) Detection of JWH-018 and JWH-073 by UPLC-MS-MS in postmortem whole blood casework. J Anal Toxicol 36:145-152
149. Shootah (2008) THC substitute. http://www.erowid.org/experiences/exp.php? ID=74873. Accessed 1 May 2012
150. Shruming - Human (2009) Notes on some legal highs - heart problems. http://www.erowid.org/experiences/exp.php?ID=79488. Accessed 1 May 2012
151. Simmons J, Cookman L, Kang C, Skinner C (2011a) Three cases of "spice" exposure. Clin Toxicol (Phila) 49:431-433
152. Simmons JR, Skinner CG, Williams J, Kang CS, Schwartz MD, Wills BK (2011b) Intoxication from smoking "spice". Ann Emerg Med 57:187-188
153. Skipper09 (2009) Can you believe it's not cannabis? http://www.erowid. org/experiences/exp.php?ID=79428. Accessed 1 May 2012
154. Sobolevsky T, Prasolov I, Rodchenkov G (2010) Detection of JWH-018 metabolites in smoking mixture post-administration urine. Forensic Sci Int 200:141-147
155. Sopris (2008) It really is like cannabis. http://www.erowid.org/ experiences/exp.php?ID=75825. Accessed 1 May 2012
156. SpacedOUTonSPICE (2009) Excessive cannabinoid agonism. http://www.erowid.org/experiences/exp.php?ID=96704. Accessed 1 May 2012
157. St. James J (2010) Doctors concerned over possible link of K2, heart damage. http://www.wfaa.com/news/health/A-dangerous-link - 100482134.html. Accessed 20 April 2012
158. Steve (2011) Next-night seizures. http://www.erowid.org/experiences/exp. php?ID=89290. Accessed 1 May 2012
159. Teltzrow R, Bosch OG (2012) Ecstatic anaesthesia: ketamine and GHB between medical use and self-experimentation. Appl Cardiopulm Pathophysiol 16:309-321
160. Teske J, Weller JP, Fieguth A, Rothamel T, Schulz Y, Troger 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 chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878:2659-2663
161. The - Pilgrim (2013) Coming out of the haze. http://www.erowid.org/ experiences/exp.php?ID=95740. Accessed 13 May 2013
162. Tofighi B, Lee JD (2012) Internet highs - seizures after consumption of synthetic cannabinoids purchased online. J Addict Med 6:240-241
163. 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 Psychiatr 22:31-33
164. Van der Veer N, Fiday J (2011) Persistent psychosis following the use of Spice. Schizophr Res 130:285-286
165. 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
166. Various (2009) Spice experience report excerpts. http://www.erowid.org/ chemicals/spice-product/spice-product-info1.shtml. Accessed 1 May 2012
167. Vearrier D, Osterhoudt KC (2010) A teenager with agitation: higher than she should have climbed. Pediatr Emerg Care 26:462-465
168. Wehrman J (2011) Fake marijuana spurs more than 4,500 calls to U.S. Poison Centers. American Association of Poison Control Centers, Alexandria
169. Wells DL, Ott CA (2011) The "new" marijuana. Ann Pharmacother 45:414-417
170. WelshSmoker (2009) Horror story. http://www.erowid.org/experiences/exp. php?ID=78880. Accessed 1 May 2012
171. 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
172. Wood DM, Davies S, Puchnarewicz M, Button J, Archer R, Ovaska H, Ramsey J, Lee T, Holt DW, Dargan PI (2010) Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity. J Med Toxicol 6:327-330
173. Wood KE (2013) Exposure to bath salts and synthetic tetrahydrocannabinol from 2009 to 2012 in the United States. J Pediatr. doi: 10.1016/j.jpeds.2012.12. 056
174. WYFF4.COM (2011) Coroner: synthetic pot killed college athlete Anderson University basketball player collapsed on Oct. 4. http://www.wyff4.com/Coroner- Synthetic-Pot-Killed-College-Athlete/-/9324882/6133626/-/10gxauh/-/index. html#ixzz1yHFVkCK7. Accessed 20 April 2012
175. 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
176. Zawilska JB (2011) "Legal highs" - new players in the old drama. Curr Drug Abuse Rev 4:122-130
177. Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K (2009) Withdrawal phenomena and dependence syndrome after the consumption of "spice gold". Deutsches Arzteblatt Int 106:464-467
178. Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R (1995) Antipsychotic effect of cannabidiol. J Clin Psychiatry 56:485-486
179. Zuardi AW, Rodrigues JA, Cunha JM (1991) Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology 104:260-264
180. Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG (1982) Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology 76:245-250
181. Zuba D, Byrska B, Maciow M (2011) Comparison of "herbal highs" composition. Anal Bioanal Chem 400:119-126