The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects

Journal of Psychopharmacology

Volumn 29, Issue 3, 2015, Pages 254-263

  Van Amsterdam, Jan ^a   Brunt, Tibor ^b   Van Den Brink, Wim ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b NETHERLANDS INSTITUTE OF MENTAL HEALTH AND ADDICTION   (Netherlands)

Author keywords

cannabis; new psychoactive substances; NPS; risk analysis; Spice

Indexed keywords

ALPHA TOCOPHEROL; CAFFEINE; CANNABIDIOL; CANNABINOID DERIVATIVE; CANNABINOID RECEPTOR AGONIST; CANNABIS; HARMALINE; NEUROLEPTIC AGENT; NICOTINE; O NORTRAMADOL; OLEAMIDE; CANNABINOID; DRONABINOL;

ACUTE KIDNEY FAILURE; ACUTE PSYCHOSIS; AGITATION; ANXIETY; APATHY; ARTICLE; ATTENTION DEFICIT DISORDER; CANNABIS ADDICTION; CARDIOTOXICITY; COGNITIVE DEFECT; CONVULSION; DELUSION; DEPRESSION; DIZZINESS; DROWSINESS; DRUG FATALITY; DRUG OVERDOSE; DRUG POTENCY; EUPHORIA; GLUCOSE BLOOD LEVEL; HALLUCINATION; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPOKALEMIA; IRRITABILITY; LETHARGY; MEMORY DISORDER; NAUSEA; PANIC; PARANOIA; POSTTRAUMATIC STRESS DISORDER; PREVALENCE; PRIORITY JOURNAL; PSYCHOSIS; RHABDOMYOLYSIS; RISK FACTOR; SCHIZOPHRENIA; SEIZURE; SELF MEDICATION; SUICIDE; TACHYCARDIA; UNSPECIFIED SIDE EFFECT; VOMITING; ANIMAL; CHEMISTRY; PSYCHOSES, SUBSTANCE-INDUCED;

ANIMALS; CANNABIDIOL; CANNABINOID RECEPTOR AGONISTS; CANNABINOIDS; CANNABIS; DRONABINOL; HUMANS; PSYCHOSES, SUBSTANCE-INDUCED;

EID: 84924750821     PISSN: 02698811     EISSN: 14617285     Source Type: Journal    
DOI: 10.1177/0269881114565142     Document Type: Article

References (141)

1. AAPCC (2012) American Association of Poison Control Centers (AAPCC). Synthetic marijuana data. Available at: http://www.aapcc.org/dnn/Portals/0/Synthetic%20Marijuana%20Data%20for%20Website%201.12.2012.pdf.
2. Andreasson S, Allebeck P, Engstrom A, et al. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet. 1987 ; 2: 1483-1486
3. Arendt M, Rosenberg R, Foldager L, et al. Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: Follow-up study of 535 incident cases. Br J Psychiat. 2005 ; 187: 510-515
4. Arseneault L, Cannon M, Poulton R, et al. Cannabis use in adolescence and risk for adult psychosis: Longitudinal prospective study. BMJ. 2002 ; 325: 1212-1213
5. Auwarter V, Dargan PI, Wood DM Novel psychoactive substances. Academic Press ; 2013 :
6. Auwarter V, Dresen S, Weinmann W, et al. 'Spice' and other herbal blends: Harmless incense or cannabinoid designer drugs?. J Mass Spectrom. 2009 ; 44: 832-837
7. Barkus E, Morrison PD, Vuletic D, et al. Does intravenous Delta9-tetrahydrocannabinol increase dopamine release? A SPET study. J Psychopharmacol. 2011 ; 25: 1462-1468
8. Barratt MJ. Silk Road: eBay for drugs. Addiction. 2012 ; 107: 683
9. Barratt MJ, Cakic V, Lenton S. Patterns of synthetic cannabinoid use in Australia. Drug Alcohol Rev. 2013 ; 32: 141-146
10. Bebarta VS, Ramirez S, Varney SM. Spice: A new "legal" herbal mixture abused by young active duty military personnel. Subst Abuse. 2012 ; 33: 191-194
11. Bernhard C, Werse B, Schell-Mack C (2013) MoSyD Jahresbericht 2012. Drogentrends in Frankfurt am Main. August 2013. Available at: http://www.uni-frankfurt.de/fb/fb04/forschung/cdr/.
12. Bhanushali GK, Jain G, Fatima H, et al. AKI associated with synthetic cannabinoids: A case series. Clin J Am Soc Nephrol. 2013 ; 8: 523-526
13. Bossong MG, van Berckel BN, Boellaard R, et al. Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology. 2009 ; 34: 759-766
14. Bossong MG, Niesink RJM. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog Neurobiol. 2010 ; 92: 370-385
15. Brakoulias V. Products containing synthetic cannabinoids and psychosis. Aust N Z J Psychiatry. 2012 ; 46: 281-282
16. Brewer TL, Brewer TL, Collins M, et al. A review of clinical manifestations in adolescent and young adults after use of synthetic cannabinoids. J Spec Pediatr Nurs. 2014 ; 19: 119-126
17. Castle DJ. Cannabis and psychosis: What causes what?. F1000 Med Rep. 2013 ; 5: 1
18. Centers for Disease Control and Prevention (CDC). Acute kidney injury associated with synthetic cannabinoid use - multiple states. MMWR Morb Mortal Wkly Rep. 2013 ; 62: 93-98
19. Chen JP, Paredes W, Li J, et al. Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacol (Berl). 1990 ; 102: 156-162
20. Madrid: Report 6 of the Clinical Committee, Ministry of Health ; 2011 :
21. Corazza O, Corazza O, Demetrovics Z, et al. 'Legal highs' an inappropriate term for 'Novel Psychoactive Drugs' in drug prevention and scientific debate. Int J Drug Policy. 2012 ; 24: 82-83
22. D'Souza DC, Perry E, MacDougall L, et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. Neuropsychopharmacol. 2004 ; 29: 1558-1572
23. DAWN (2012) Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Behavioral Health Statistics and Quality. (December4, 2012). The DAWN Report: Drug-related emergency department visits involving synthetic cannabinoids. Rockville, MD. Available at: http://www.samhsa.gov/data/2k12/DAWN105/SR105-synthetic-marijuana.htm.
24. Di Forti M, Morgan C, Dazzan P, et al. High-potency cannabis and the risk of psychosis. Brit J Psychiat. 2009 ; 195: 488-491
25. Di Forti M, Sallis H, Allegri F, et al. Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. Schizophr Bull. 2014 ;:
26. Dillon P, Copeland J. Synthetic cannabinoids: The Australian experience. NCPIC Bulletin Series. 2012 ; 13: 1-10
27. Dossou KSS, Devkota KP, Kavanagh PV, et al. Development and preliminary validation of a plate-based CB1/CB2 receptor functional assay. Anal Biochem. 2013 ; 437: 138-143
28. Dragt S, Nieman DH, Schultze-Lutter F, et al. Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis. Acta Psychiatr Scand. 2012 ; 125: 45-53
29. Dresen S, Ferreiros N, Putz M, et al. Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom. 2010 ; 45: 1186-1194
30. Durand D, Durand D, Delgado LL, et al. Psychosis and severe rhabdomyolysis associated with synthetic cannabinoid use. Clin Schizophr Relat Psychoses. 2013 ;: 1-13
31. Egertova M, Elphick MR. Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CB. J Comp Neurol. 2000 ; 422: 159-171
32. Elphick MR, Egertova M. The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond B Biol Sci. 2001 ; 356: 381-408
33. EMCDDA (2009) European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Thematic paper. Understanding the Spice Phenomenon. Available at: http://www.emcdda.europa.eu/attachements.cfm/att-80086-EN-Spice%20Thematic%20paper%20-%20final%20version.pdf.
34. EMCDDA (2011) European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Responding to new psychoactive substances. Briefing of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Drugs in focus. 2nd issue. Available at: www.emcdda.europa.eu/publications/drugs-in-focus/responding-to-newpsychoactive-substances. Lisbon.
35. EMCDDA (2013) Perspectives on drugs. Synthetic cannabinoids in Europe (update May2013). Available at: http://www.emcdda.europa.eu/attachements.cfm/att-212361-EN-EMCDDA-POD-2013-Synthetic%20cannabinoids.pdf.
36. Fattore L, Fratta W. Beyond THC: The new generation of cannabinoid designer drugs. Front Behav Neurosci. 2011 ; 5: 60
37. Foldy C, Neu A, Jones MV, et al. Presynaptic, activity-dependent modulation of cannabinoid type 1 receptor-mediated inhibition of GABA release. J Neurosci. 2006 ; 26: 1465-1469
38. Forrester MB. Adolescent synthetic cathinone exposures reported to Texas poison centers. Pediatr Emerg Care. 2013 ; 29: 151-155
39. Forrester MB, Kleinschmidt K, Schwarz E, et al. Synthetic cannabinoid exposures reported to Texas poison centers. J Addict Dis. 2011 ; 30: 351-358
40. Forrester MB, Kleinschmidt K, Schwarz E, et al. Synthetic cannabinoid and marijuana exposures reported to poison centers. Hum Exp Toxicol. 2012 ; 31: 1006-1011
41. French ED. Delta9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. Neurosci Lett. 1997 ; 226: 159-162
42. Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev. 2003 ; 83: 1017-1066
43. Fried PA, Watkinson B, Gray R. Neurocognitive consequences of marihuana - a comparison with pre-drug performance. Neurotoxicol Teratol. 2005 ; 27: 231-239
44. Galvez-Buccollini JA, Proal AC, Tomaselli V, et al. Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis. Schizophr Res. 2012 ; 139: 157-160
45. Ginsburg BC, McMahon LR, Sanchez JJ, et al. Purity of synthetic cannabinoids sold online for recreational use. J Anal Toxicol. 2012 ; 36: 66-68
46. Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: A detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neurosci. 1997 ; 77: 299-318
47. Goonawardena AV, Riedel G, Hampson RE. Cannabinoids alter spontaneous firing, bursting, and cell synchrony of hippocampal principal cells. Hippocampus. 2011 ; 21: 520-531
48. Guhring H, Schuster J, Hamza M, et al. HU-210 shows higher efficacy and potency than morphine after intrathecal administration in the mouse formalin test. Eur J Pharmacol. 2001 ; 429: 127-134
49. Gunderson EW, Haughey HM, it-Daoud N, et al. "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. 2012 ; 21: 320-326
50. Hermanns-Clausen M, Kneisel S, Hutter M, et al. Acute intoxication by synthetic cannabinoids - four case reports. Drug Test Anal. 2013a ; 5: 790-794
51. Hermanns-Clausen M, Kneisel S, Szabo B, et al. Acute toxicity due to the confirmed consumption of synthetic cannabinoids: Clinical and laboratory findings. Addiction. 2013b ; 108: 534-544
52. Hirvonen J, Goodwin RS, Li CT, et al. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Mol Psychiatry. 2012 ; 17: 642-649
53. Hoffman AF, Lupica CR. Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J Neurosci. 2000 ; 20: 2470-2479
54. Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev. 2002 ; 54: 161-202
55. Hoyte CO, Jacob J, Monte AA, et al. A characterization of synthetic cannabinoid exposures reported to the National Poison Data System in 2010. Ann Emerg Med. 2012 ; 60: 435-438
56. Hu X, Primack BA, Barnett TE, et al. College students and use of K2: An emerging drug of abuse in young persons. Subst Abuse Treat Prev Policy. 2011 ; 6: 16
57. Hudson S, Ramsey J. The emergence and analysis of synthetic cannabinoids. Drug Test Anal. 2011 ; 3: 466-478
58. Hurst D, Loeffler G, McLay R (2011a) Synthetic cannabinoid agonist induced psychosis: A case series. APA poster. Naval Medical Centre, San Diego. Available at: http://www.ncis.navy.mil/PI/CRP/Documents/Spice%20APA%20poster.pdf.
59. Hurst D, Loeffler G, McLay R. Psychosis associated with synthetic cannabinoid agonists: A case series. Am J Psychiatry. 2011b 1119 ; 168 :
60. Izzo AA, Borrelli F, Capasso R, et al. Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009 ; 30: 515-527
61. Javitt DC. Glutamate and schizophrenia: Phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions. Int Rev Neurobiol. 2007 ; 78: 69-108
62. Jerry J, Collins G, Streem D. Synthetic legal intoxicating drugs: The emerging 'incense' and 'bath salt' phenomenon. Cleve Clin J Med. 2012 ; 79: 258-264
63. Johnson LA, Johnson RL, Alfonzo C. Spice: A legal marijuana equivalent. Mil Med. 2011 ; 176: 718-720
64. Katona I, Sperlagh B, Magloczky Z, et al. GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus. Neurosci. 2000 ; 100: 797-804
65. Kikura-Hanajiri R, Uchiyama N, Goda Y. Survey of current trends in the abuse of psychotropic substances and plants in Japan. Leg Med (Tokyo). 2011 ; 13: 109-115
66. Kikura-Hanajiiri R, Uchiyama N, Kawamura M, et al. Changes in the prevalence of synthetic cannabinoids and cathinone derivatives in Japan until early 2012. Forensic Toxicol. 2013 ; 31: 44-53
67. King LA. Legal controls on cannabimimetics: An international dilemma?. Drug Test Anal. 2014 ; 6: 80-87
68. Koethe D, Gerth CW, Neatby MA, et al. Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness. Schizophr Res. 2006 ; 88: 142-150
69. Kolliakou A, Joseph C, Ismail K, et al. Why do patients with psychosis use cannabis and are they ready to change their use?. Int J Dev Neurosci. 2011 ; 29: 335-346
70. Kuepper R, Morrison PD, van Os J, et al. Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines. Schizophr Res. 2010 ; 121: 107-117
71. Kuepper R, van Os J, Lieb R, et al. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ. 2011 ; 342: d738
72. Lan R, Gatley J, Lu Q, et al. Design and synthesis of the CB1 selective cannabinoid antagonist AM281: A potential human SPECT ligand. AAPS PharmSci. 1999 ; 1: E4
73. Lank PM, Pines E, Mycyk MB. Emergency physicians' knowledge of cannabinoid designer drugs. West J Emerg Med. 2013 ; 14: 467-470
74. Lapoint J, James LP, Moran CL, et al. Severe toxicity following synthetic cannabinoid ingestion. Clin Toxicol (Phila). 2011 ; 49: 760-764
75. Large M, Sharma S, Compton MT, et al. Cannabis use and earlier onset of psychosis: A systematic meta-analysis. Arch Gen Psychiatry. 2011 ; 68: 555-561
76. Lee SH, Soltesz I. Requirement for CB1 but not GABAB receptors in the cholecystokinin mediated inhibition of GABA release from cholecystokinin expressing basket cells. J Physiol. 2011 ; 589: 891-902
77. Leweke F, Koethe D, Gerth C. Cannabidiol as an anti-psychotic: A double-blind, controlled clinical trial of cannabidiol versus amisulpiride in acute schizophrenia. 15th Annual Symposium on Cannabinoids ; 2005 ; 2005..
78. Lindigkeit R, Boehme A, Eiserloh I, et al. Spice: A never ending story?. Forensic Sci Int. 2009 ; 191: 58-63
79. Loeffler G, Hurst D, Penn A, et al. 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. 2012 ; 177: 1041-1048
80. Martinotti G, Di Iorio G, Sepede G, et al. Cannabis use and psychosis: Theme introduction. Curr Pharm Des. 2012 ; 18: 4991-4998
81. Martinotti G, Di lorio G, Tedeschi D, et al. Prevalence and intensity of basic symptoms among cannabis users: An observational study. Am J Drug Alcohol Abuse. 2011 ; 37: 111-116
82. Mir A, Obafemi A, Young A, et al. Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics. 2011 ; 128: e1622-e1627
83. The Mixmag/Guardian drug survey.. 2012 ;:
84. Moore E, Mancuso SG, Slade T, et al. The impact of alcohol and illicit drugs on people with psychosis: The second Australian National Survey of Psychosis. Aust N Z J Psychiatry. 2012 ; 46: 864-878
85. Moore THM, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: A systematic review. Lancet. 2007 ; 370: 319-328
86. Morgan CJA, Curran HV. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiat. 2008 ; 192: 306-307
87. Morgan CJ, Page E, Schaefer C, et al. Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms. Br J Psychiatry. 2013 ; 202: 381-382
88. Morgan CJA, Gardener C, Schafer G, et al. Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being. Psychol Med. 2012 ; 42: 391-400
89. Morgan CJA, Schafer G, Freeman TP, et al. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: Naturalistic study. Br J Psychiat. 2010 ; 197: 285-290
90. Morrison PD, Stone JM. Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation. Hum Psychopharmacol. 2011 ; 26: 77-80
91. Muller H, Huttner HB, Kohrmann M, et al. Panic attack after spice abuse in a patient with ADHD. Pharmacopsychiat. 2010 ; 43: 152-153
92. Murray RM, Morrison PD, Henquet C, et al. Cannabis, the mind and society: The hash realities. Nat Rev Neurosci. 2007 ; 8: 885-895
93. Oluwabusi OO, Lobach L, Akhtar U, et al. Synthetic cannabinoid-induced psychosis: Two adolescent cases. J Child Adolesc Psychopharmacol. 2012 ; 22: 393-395
94. London: Home Office ; 2012 :
95. Papanti D, Schifano F, Botteon G, et al. "Spiceophrenia": A systematic overview of "Spice"-related psychopathological issues and a case report. Hum Psychopharmacol. 2013 ; 28: 379-389
96. Patton AL, Patton AL, Chimalakonda KC, et al. K2 toxicity: Fatal case of psychiatric complications following AM2201 exposure. J Forensic Sci. 2013 ; 58: 1676-1680
97. Peglow S, Buchner J, Briscoe G. Synthetic cannabinoid induced psychosis in a previously nonpsychotic patient. Am J Addict. 2012 ; 21: 287-288
98. Pertwee RG. The diverse CB1 and CB2-receptor pharmacology of three plant cannabinoids: Delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008a ; 153: 199-215
99. Pertwee RG. Ligands that target cannabinoid receptors in the brain: From THC to anandamide and beyond. Addict Biol. 2008b ; 13: 147-159
100. Pertwee RG, Ross RA, Craib SJ, et al. (-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens. Eur J Pharmacol. 2002 ; 456: 99-106
101. Piggee C. Investigating a not-so-natural high. Anal Chem. 2009 ; 81: 3205-3207
102. Pistis M, Porcu G, Melis M, et al. Effects of cannabinoids on prefrontal neuronal responses to ventral tegmental area stimulation. Eur J Neurosci. 2001 ; 14: 96-102
103. Psychoyos D, Vinod KY. Marijuana, Spice 'herbal high', and early neural development: implications for rescheduling and legalization. Drug Test Anal. 2013 ; 5: 27-45
104. Reynaud C, Strong J (2010) Indianola teen's tragic death blamed on incense. Des Moines Register 2010. Available at: http://www.bluelight.ru/vb/threads/509136-Indianola-teen-s-tragic-death-blamed-on-incense.
105. Sanchez-Blazquez P, Rodriguez-Munoz M, Garzon J. The cannabinoid receptor 1 associates with NMDA receptors to produce glutamatergic hypofunction: Implications in psychosis and schizophrenia. Front Pharmacol. 2014 ; 4: 169
106. Schier ARdM, Ribeiro NPdO, de Oliveira e Silva AC, et al. Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug. Rev Bras Psiquiatr. 2012 ; 1: S104 - S110
107. Schifano F, Corazza O, Deluca P, et al. Psychoactive drug or mystical incense? Overview of the online available information on Spice products. Int J Culture Ment Health. 2009 ; 2: 137-144
108. Schneir AB, Baumbacher T. Convulsions associated with the use of a synthetic cannabinoid product. J Med Toxicol. 2012 ; 8: 62-64
109. Schneir AB, Cullen J, Ly BT. "Spice" girls: Synthetic cannabinoid intoxication. J Emerg Med. 2011 ; 40: 296-299
110. Schubart CD, van Gastel WA, Breetvelt EJ, et al. Cannabis use at a young age is associated with psychotic experiences. Psychol Med. 2011a ; 41: 1301-1310
111. Schubart CD, Sommer IEC, van Gastel WA, et al. Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr Res. 2011b ; 130: 216-221
112. Seely KA, Lapoint J, Moran JH, et al. Spice drugs are more than harmless herbal blends: A review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry. 2012 ; 39: 234-243
113. Simmons J, Cookman L, Kang C, et al. Three cases of "spice" exposure. Clin Toxicol (Phila). 2011a ; 49: 431-433
114. Simmons JR, Skinner CG, Williams J, et al. Intoxication from smoking "spice". Ann Emerg Med. 2011b ; 57: 187-188
115. Simonato P, Corazza O, Santonastaso P, et al. Novel psychoactive substances as a novel challenge for health professionals: Results from an Italian survey. Hum Psychopharmacol. 2013 ; 28: 324-331
116. Stokes PR, Mehta MA, Curran HV, et al. Can recreational doses of THC produce significant dopamine release in the human striatum?. Neuroimage. 2009 ; 48: 186-190
117. Szabo B, Siemes S, Wallmichrath I. Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. Eur J Neurosci. 2002 ; 15: 2057-2061
118. Thomas A, Baillie GL, Phillips AM, et al. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007 ; 150: 613-623
119. Thornton SL, Wood C, Friesen MW, et al. Synthetic cannabinoid use associated with acute kidney injury. Clin Toxicol (Phila). 2013 ; 51: 189-190
120. Uchiyama N, Kikura-Hanajiri R, Ogata J, et al. Chemical analysis of synthetic cannabinoids as designer drugs in herbal products. Forensic Sci Int. 2010 ; 198: 31-38
121. Univ Michigan (2011) University of Michigan News Service. Marijuana use continues to rise among U.S. teens, while alcohol use hits historic lows. Available at: http://www.monitoringthefuture.org/pressreleases/11drugpr.pdf.
122. Synthetic Cannabinoids in Herbal Products.. 2011 ;:
123. Van Amsterdam JGC, Nutt DJ, van den Brink W. Generic legislation of new psychoactive drugs. J Psychopharmacol. 2013 ; 27: 317-324
124. Van Amsterdam JGC, Opperhuizen A, van den Brink W. Cannabis als risicofactor van schizofrenie. Tijdschr Psychol. 2004 ; 46: 515-524
125. Van Os J, Bak M, Hanssen M, et al. Cannabis use and psychosis: A longitudinal population-based study. Am J Epidemiol. 2002 ; 156: 319-327
126. Vandrey R, Dunn KE, Fry JA, et al. A survey study to characterize use of Spice products (synthetic cannabinoids). Drug Alcohol Depend. 2012 ; 120: 238-241
127. Vearrier D, Osterhoudt KC. A teenager with agitation: Higher than she should have climbed. Pediatr Emerg Care. 2010 ; 26: 462-465
128. Verdoux H, Gindre C, Sorbara F, et al. Effects of cannabis and psychosis vulnerability in daily life: An experience sampling test study. Psychol Med. 2003 ; 33: 23-32
129. WerseB (2010) Spice, Smoke, Sence & Co. - herbal mixtures containing cannabinoids: Use and motivation for use against the backdrop of changing laws. Report from the German Federal Ministry of Health Division 125: Addiction and Drugs.
130. Wiley JL, Marusich JA, Huffman JW. (2011) Hijacking of basic research: The case of synthetic cannabinoids. Research report. Research Triangle Institute Press publication OP-0007-1111. Available at: http://www.rti.org/pubs/op-0007-1111-wiley.pdf.
131. Wiley JL, Marusich JA, Huffmann JW. Moving around the molecule: Relationship between chemical structure and in vivo activity of synthetic cannabinoids. Life Sci. 2013 ;:
132. Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002 ; 296: 678-682
133. Winstock AR (2014) The Global Drug Survey 2014. Findings. Available at: http://www.globaldrugsurvey.com/facts-figures/the-global-drug-survey-2014-findings/.
134. Winstock AR, Barratt MJ. Synthetic cannabis: A comparison of patterns of use and effect profile with natural cannabis in a large global sample. Drug Alcohol Depend. 2013 ; 131: 106-111
135. Wylie AS, Scott RT, Burnett SJ. Psychosis due to "skunk". BMJ. 1995 ; 311: 125
136. Young AC, Schwarz E, Medina G, et al. Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation. Am J Emerg Med. 2012 ; 30: 1320-1327
137. Zimmermann US, Winkelmann PR, Pilhatsch M, et al. Withdrawal phenomena and dependence syndrome after the consumption of "spice gold". Dtsch Arztebl Int. 2009 ; 106: 464-467
138. Zuardi AW, Crippa JAS, Hallak JEC, et al. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006a ; 39: 421-429
139. Zuardi AW, Crippa JA, Hallak JE, et al. A critical review of the antipsychotic effects of Cannabidiol: 30 years of a translational investigation. Curr Pharm Des. 2012 ; 18: 5131-5140
140. Zuardi AW, Hallak JEC, Dursun SM, et al. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006b ; 20: 683-686
141. Zuba D, Byrska B, Maciow M. Comparison of "herbal highs" composition. Anal Bioanal Chem. 2011 ; 400: 119-126