The synthetic cannabinoids phenomenon: from structure to toxicological properties. A review

References

• Abbate V, Schwenk M, Presley BC, Uchiyama N. 2018. The ongoing challenge of novel psychoactive drugs of abuse. Part I. Synthetic cannabinoids (IUPAC Technical Report). Pure Appl Chem. 90(8):1255–1282.
   Web of Science ®Google Scholar
• Advisory Council on the Misuse of Drugs. ‘Third generation’ synthetic Cannabinoids; 2014. [accessed 2019 Jul 16]. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/380161/CannabinoidsReport.pdf.
   Google Scholar
• Aizpurua-Olaizola O, Elezgarai I, Rico-Barrio I, Zarandona I, Etxebarria N, Usobiaga A. 2017. Targeting the endocannabinoid system: future therapeutic strategies. Drug Discov Today. 22(1):105–110.
   PubMed Web of Science ®Google Scholar
• Alipour A, Patel PB, Shabbir Z, Gabrielson S. 2019. Review of the many faces of synthetic cannabinoid toxicities. Ment Health Clin. 9(2):93–99.
   PubMedGoogle Scholar
• Altintas M, Inanc L, Oruc GA, Arpacioglu S, Gulec H. 2016. Clinical characteristics of synthetic cannabinoid-induced psychosis in relation to schizophrenia: a single-center cross-sectional analysis of concurrently hospitalized patients. Neuropsychiatr Dis Treat. 12:1893–1900.
   PubMed Web of Science ®Google Scholar
• Andre CM, Hausman J-F, Guerriero G. 2016. Cannabis sativa: the plant of the thousand and one molecules. Front Plant Sci. 7:19–19.
   PubMed Web of Science ®Google Scholar
• Araújo AM, Valente MJ, Carvalho M, Dias da Silva D, Gaspar H, Carvalho F, de Lourdes Bastos M, Guedes de Pinho P. 2015. Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of ‘legal high’ packages containing synthetic cathinones. Arch Toxicol. 89(5):757–771.
   PubMed Web of Science ®Google Scholar
• Ashino T, Hakukawa K, Itoh Y, Numazawa S. 2014. Inhibitory effect of synthetic cannabinoids on CYP1A activity in mouse liver microsomes. J Toxicol Sci. 39(6):815–820.
   PubMed Web of Science ®Google Scholar
• Aso E, Ferrer I. 2016. CB2 cannabinoid receptor as potential target against Alzheimer’s Disease. Front Neurosci. 10:243–243.
   PubMed Web of Science ®Google Scholar
• Aung MM, Griffin G, Huffman JW, Wu M-J, 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(2):133–140.
   PubMed Web of Science ®Google Scholar
• Auwärter V, Dargan PI, Wood DM. 2013. Chapter 13 - synthetic cannabinoid receptor agonists. In: Dargan PI, Wood DM, editors. Novel psychoactive substances. Boston: Academic Press; p. 317–343.
   Google Scholar
• 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(5):832–837.
   PubMed Web of Science ®Google Scholar
• Banister SD, Moir M, Stuart J, Kevin RC, Wood KE, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Glass M, et al. 2015. Pharmacology of Indole and Indazole synthetic cannabinoid designer drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA. ACS Chem Neurosci. 6(9):1546–1559.
   PubMed Web of Science ®Google Scholar
• Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Hibbs DE, Glass M, et al. 2015. Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135. ACS Chem Neurosci. 6(8):1445–1458.
   PubMed Web of Science ®Google Scholar
• Barratt M, Seear K, Lancaster K. 2017. A critical examination of the definition of 'psychoactive effect' in Australian drug legislation. Int J Drug Policy. 40:16–25.
   PubMed Web of Science ®Google Scholar
• Baumann MH, Glennon RA, Wiley JL. 2017. Neuropharmacology of New Psychoactive Substances (NPS): The science behind the headlines. Switzerland: Springer International Publishing.
   Google Scholar
• Blundell MS, Dargan PI, Wood DM. 2018. The dark cloud of recreational drugs and vaping. Qjm-Int J Med. 111(3):145–148.
   PubMed Web of Science ®Google Scholar
• Breitbarth AK, Morgan J, Jones AL. 2018. E-cigarettes-An unintended illicit drug delivery system. Drug Alcohol Depend. 192:98–111.
   PubMed Web of Science ®Google Scholar
• Brents LK, Prather PL. 2014. The K2/Spice phenomenon: emergence, identification, legislation and metabolic characterization of synthetic cannabinoids in herbal incense products. Drug Metab Rev. 46(1):72–85.
   PubMed Web of Science ®Google Scholar
• 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(7):e21917.
   PubMed Web of Science ®Google Scholar
• Britannica E. 2018. Cannabis. Encyclopaedia Britannica, inc. [accessed 2019 Apr 17]. https://www.britannica.com/plant/cannabis-plant.
   Google Scholar
• Brock TG. 2012. The Metabolism of JWH-type Synthetic Cannabinoids. [accessed 2019 Apr 22]. https://www.caymanchem.com/news/metabolism-of-jwh-type-synthetic-cannabinoids.
   Google Scholar
• Buser GL, Gerona RR, Horowitz BZ, Vian KP, Troxell ML, Hendrickson RG, Houghton DC, Rozansky D, Su SW, Leman RF. 2014. Acute kidney injury associated with smoking synthetic cannabinoid. Clin Toxicol (Phila). 52(7):664–673.
   PubMed Web of Science ®Google Scholar
• Cannaert A, Storme J, Franz F, Auwärter V, Stove C. 2016. Detection and activity profiling of synthetic cannabinoids and metabolites with a newly developed bio-assay. Anal Chem. 88(23):11476–11485.
   PubMed Web of Science ®Google Scholar
• Cannaert A, Vandeputte M, Wille SMR, Stove CP. 2019. Activity-based reporter assays for the screening of abused substances in biological matrices. Crit Rev Toxicol. 49(2):95–109.
   PubMed Web of Science ®Google Scholar
• Carlier J, Wohlfarth A, Salmeron BD, Scheidweiler KB, Huestis MA, Baumann MH. 2018. Pharmacodynamic effects, pharmacokinetics, and metabolism of the synthetic cannabinoid AM-2201 in male rats. J Pharmacol Exp Ther. 367(3):543–550.
   PubMed Web of Science ®Google Scholar
• Carlsson A. 2016. Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones [Dissertation]. Sweden: Linköping University.
   Google Scholar
• Carvalho Â, Hansen EH, Kayser O, Carlsen S, Stehle F. 2017. Designing microorganisms for heterologous biosynthesis of cannabinoids. FEMS Yeast Research. 17(4):fox037.
   Web of Science ®Google Scholar
• Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA. 2014. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend. 144:12–41.
   PubMed Web of Science ®Google Scholar
• Castaneto MS, Wohlfarth A, Pang S, Zhu M, Scheidweiler KB, Kronstrand R, Huestis MA. 2015. Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry. Forensic Toxicol. 33(2):295–310.
   Web of Science ®Google Scholar
• Castaneto MS, Wohlfarth A, Desrosiers NA, Hartman RL, Gorelick DA, Huestis MA. 2015. Synthetic cannabinoids pharmacokinetics and detection methods in biological matrices. Drug Metab Rev. 47(2):124–174.
   PubMed Web of Science ®Google Scholar
• Caviness CM, Tzilos G, Anderson BJ, Stein MD. 2015. Synthetic cannabinoids: use and predictors in a community sample of young adults. Subst Abus. 36(3):368–373.
   PubMed Web of Science ®Google Scholar
• CDC. 2013. Centers for Disease Control and Prevention. Acute kidney injury associated with synthetic cannabinoid use–multiple states, 2012. Morb Mortal Wkly Rep. 62(6):93–98.
   PubMed Web of Science ®Google Scholar
• Chakravarti B, Ravi J, Ganju RK. 2014. Cannabinoids as therapeutic agents in cancer: current status and future implications. Oncotarget. 5(15):5852–5872.
   PubMedGoogle Scholar
• Chimalakonda KC, Seely KA, Bratton SM, Brents LK, Moran CL, Endres GW, James LP, Hollenberg PF, Prather PL, Radominska-Pandya A. 2012. Cytochrome P450-mediated oxidative metabolism of abused synthetic cannabinoids found in K2/Spice: identification of novel cannabinoid receptor ligands. Drug Metab Dispos. 40(11):2174–2184.
   PubMed Web of Science ®Google Scholar
• Chopra N. 2015. Fake marijuana. A Real Problem. 10. https://ajp.psychiatryonline.org/pb/assets/raw/journals/residents-journal/2015/June_2015.pdf
   Google Scholar
• Clinic K. 2016. What are cannabinoids? Kalapa Clinic. [accessed 2019 Jul 24]. https://www.kalapa-clinic.com/en/cannabinoids-type/.
   Google Scholar
• Cohen K, Kapitány-Fövény M, Mama Y, Arieli M, Rosca P, Demetrovics Z, Weinstein A. 2017. The effects of synthetic cannabinoids on executive function. Psychopharmacology (Berl). 234(7):1121–1134.
   PubMed Web of Science ®Google Scholar
• Cohen K, Weinstein A. 2018. The effects of cannabinoids on executive functions: evidence from cannabis and synthetic cannabinoids—a systematic review. Brain Sci. 8(3):40.
   PubMed Web of Science ®Google Scholar
• Cohen K, Weinstein AM. 2018. Synthetic and non-synthetic cannabinoid drugs and their adverse effects-a review from public health prospective. Front Public Health. 6:162.
   PubMed Web of Science ®Google Scholar
• Cooper ZD. 2016. Adverse effects of synthetic cannabinoids: management of acute toxicity and withdrawal. Curr Psychiatry Rep. 18(5):52.
   PubMed Web of Science ®Google Scholar
• De Brabanter N, Esposito S, Tudela E, Lootens L, Meuleman P, Leroux-Roels G, Deventer K, Van Eenoo P. 2013. In vivo and in vitro metabolism of the synthetic cannabinoid JWH-200. Rapid Commun Mass Spectrom. 27(18):2115–2126.
   PubMed Web of Science ®Google Scholar
• De Luca MA, Fattore L. 2018. Therapeutic use of synthetic cannabinoids: still an openIssue? Clin Ther. 40(9):1457–1466.
   PubMed Web of Science ®Google Scholar
• Debruyne D, Le Boisselier R. 2015. Emerging drugs of abuse: current perspectives on synthetic cannabinoids. Subst Abuse Rehabil. 6:113–129.
   PubMed Web of Science ®Google Scholar
• Deng H, Verrico CD, Kosten TR, Nielsen DA. 2018. Psychosis and synthetic cannabinoids. Psychiatry Res. 268:400–412.
   PubMed Web of Science ®Google Scholar
• Diao X, Carlier J, Zhu M, Pang S, Kronstrand R, Scheidweiler KB, Huestis MA. 2017. In vitro and in vivo human metabolism of a new synthetic cannabinoid NM-2201 (CBL-2201). Forensic Toxicol. 35(1):20–32.
   PubMed Web of Science ®Google Scholar
• Diao X, Huestis MA. 2017. Approaches, challenges, and advances in metabolism of new synthetic cannabinoids and identification of optimal urinary marker metabolites. Clin Pharmacol Ther. 101(2):239–253.
   PubMed Web of Science ®Google Scholar
• Diao X, Huestis MA. 2019. New synthetic cannabinoids metabolism and strategies to best identify optimal marker metabolites. Front Chem. 7:109–109.
   PubMed Web of Science ®Google Scholar
• 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(10):1186–1194.
   PubMed Web of Science ®Google Scholar
• Drug Enforcement Administration (DEA). 2011. Schedules of controlled substances: temporary placement of five synthetic cannabinoids into schedule I. p. 11075–11078. https://www.deadiversion.usdoj.gov/fed_regs/rules/2011/fr0301.htm
   Google Scholar
• Duccio P, Fabrizio S, Laura O. 2018. Chapter 9, synthetic cannabinoids and synthetic cannabinoid-induced psychotic disorders. In: Compton MT, Manseau MW, editors. The complex connection between cannabis and schizophrenia. San Diego: Academic Press; p. 199–220.
   Google Scholar
• ElSohly MA, Ahmed S, Gul SW, Gul W. 2019. Chapter 22 - Review of synthetic cannabinoids on the illicit drug market. In: Dasgupta A, editor. Critical issues in alcohol and drugs of abuse testing 2nd ed. San Diego, USA: Academic Press; p. 273–319.
   Google Scholar
• EMCDDA 2009. Understanding the ‘Spice’ phenomenon. [accessed 2019 Feb 23]. http://www.emcdda.europa.eu/publications/thematic-papers/understanding-spice-phenomenon_en.
   Google Scholar
• EMCDDA 2015. Synthetic cannabinoids and “Spice” drug profile. [accessed 2019 Apr 15]. http://www.emcdda.europa.eu/publications/drug-profile/synthetic-cannabinoids-drug-profile_en.
   Google Scholar
• EMCDDA 2017. Perspectives On Drugs: Synthetic cannabinoids in Europe. [updated June; accessed 2019 Apr 12]. http://www.emcdda.europa.eu/publications/pods/synthetic-cannabinoids_en.
   Google Scholar
• EMCDDA 2018. Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. [accessed 2019 Feb 23]. http://www.emcdda.europa.eu/system/files/publications/8870/2018-2489-td0118414enn.pdf.
   Google Scholar
• EMCDDA. 2019a. EU drug markets report. Publications O ce of the European Union. [accessed 2019 Oct 2]. http://www.emcdda.europa.eu/system/files/publications/12078/20192630_TD0319332ENN_PDF.pdf.
   Google Scholar
• EMCDDA. 2019b. European drug report 2019: trends and developments. [accessed]. http://www.emcdda.europa.eu/edr2019_en.
   Google Scholar
• Emery DW, Iceman CR, Hayes SM. 2018. Geographic variability of active ingredients in spice as an indicator of mechanisms of distribution and manufacture within Alaska. J Young Investig. 34(4):7–16.
   PubMedGoogle Scholar
• Evren C, Bozkurt M. 2013. Synthetic cannabinoids: crisis of the decade Düşünen Adam. J Psychiatr Neurol Sci. 26:1–11.
   Google Scholar
• Fantegrossi WE, Moran JH, Radominska-Pandya A, Prather PL. 2014. Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ(9)-THC: mechanism underlying greater toxicity? Life Sci. 97(1):45–54.
   PubMed Web of Science ®Google Scholar
• Farrugia LA, Rhyee SH, Calello DP, Campleman SL, Riederer AM, Malashock HR, Pizon A, Wiegand T, Wax PM, Brent J, et al. 2017. The toxicology investigators consortium case registry-the 2016 experience. J Med Toxicol. 13(3):203–226.
   PubMed Web of Science ®Google Scholar
• Farrugia LA, Rhyee SH, Campleman SL, Judge B, Kao L, Pizon A, Porter L, Riederer AM, Wiegand T, Calello D, et al. 2018. The toxicology investigators consortium case registry-the 2017 annual report]. J Med Toxicol. 14(3):182–211.
   PubMed Web of Science ®Google Scholar
• Fattore L, Fratta W. 2011. Beyond THC: the new generation of cannabinoid designer drugs [Review]. Front Behav Neurosci. 5(60):1–12.
   Google Scholar
• Feng LY, Battulga A, Han E, Chung H, Li JH. 2017. New psychoactive substances of natural origin: a brief review. J Food Drug Anal. 25(3):461–471.
   PubMed Web of Science ®Google Scholar
• Gamage TF, Farquhar CE, Lefever TW, Marusich JA, Kevin RC, McGregor IS, Wiley JL, Thomas BF. 2018. Molecular and behavioral pharmacological characterization of abused synthetic cannabinoids MMB- and MDMB-FUBINACA, MN-18, NNEI, CUMYL-PICA, and 5-Fluoro-CUMYL-PICA. J Pharmacol Exp Ther. 365(2):437–446.
   PubMedGoogle Scholar
• Garner CE, Smith S, Bardhan PK, Ratcliffe NM, Probert CS. 2009. A pilot study of faecal volatile organic compounds in faeces from cholera patients in Bangladesh to determine their utility in disease diagnosis. Trans R Soc Trop Med Hyg. 103(11):1171–1173.
   PubMed Web of Science ®Google Scholar
• Gertsch J, Pertwee RG, Di Marzo V. 2010. Phytocannabinoids beyond the Cannabis plant - do they exist? Br J Pharmacol. 160(3):523–529.
   PubMed Web of Science ®Google Scholar
• Gonçalves JL, Alves VL, Aguiar J, Teixeira HM, Câmara JS. 2019. Synthetic cathinones: an evolving class of new psychoactive substances. Crit Rev Toxicol. 49(7):549–566.
   Web of Science ®Google Scholar
• Grigoryev A, Melnik A, Savchuk S, Simonov A, Rozhanets V. 2011. Gas and liquid chromatography-mass spectrometry studies on the metabolism of the synthetic phenylacetylindole cannabimimetic JWH-250, the psychoactive component of smoking mixtures. J Chromatogr B Analyt Technol Biomed Life Sci. 879(25):2519–2526.
   PubMed Web of Science ®Google Scholar
• Hakimian D, Tomer O, Hiller N, Heyman SN, Israel S. 2017. Fatal mesenteric ischemia induced by synthetic cannabinoids: a case report and literature review. Case Rep Emerg Med. 2017:6964078–6964078.
   PubMedGoogle Scholar
• Halawa OI, Furnish TJ, Wallace MS. 2018. Chapter 56 - role of cannabinoids in pain management. In: Benzon HT, Raja SN, Liu SS, editors. Essentials of pain medicine. 4th ed. Philadelphia, USA: Elsevier; p. 509–520.
   Google Scholar
• Henriques S, Silva JP, Hsu K. 2018. Overview on new psychoactive substances in Portugal. Centro de Investigação e Estudos de Sociologia Instituto Universitário de Lisboa.
   Google Scholar
• Hervás ES. 2017. Synthetic cannabinoids: characteristics, use and clinical implications. Arch Psychiatry Psychother. 19(2):42–48.
   Web of Science ®Google Scholar
• Hess C, Schoeder CT, Pillaiyar T, Madea B, Müller CE. 2016. Pharmacological evaluation of synthetic cannabinoids identified as constituents of spice. Forensic Toxicol. 34:329–343.
   PubMed Web of Science ®Google Scholar
• Holm NB, Nielsen LM, Linnet K. 2015. CYP3A4 mediates oxidative metabolism of the synthetic cannabinoid AKB-48. AAPS J. 17(5):1237–1245.
   PubMed Web of Science ®Google Scholar
• Home Office 2018. Review of the Psychoactive Substances Act 2016. [accessed 2019 Jul 17]. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/756896/Review_of_the_Psychoactive_Substances_Act__2016___web_.pdf.
   Google Scholar
• Hourani W, Alexander S. 2018. Cannabinoid ligands, receptors and enzymes: Pharmacological tools and therapeutic potential. Brain Neurosci Adv. 2:2398212818783908–8.
   Google Scholar
• Hruba L, McMahon LR. 2014. The cannabinoid agonist HU-210: pseudo-irreversible discriminative stimulus effects in rhesus monkeys. Eur J Pharmacol. 727:35–42.
   PubMed Web of Science ®Google Scholar
• 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(5):252–260.
   PubMed Web of Science ®Google Scholar
• Huffman JW, Padgett LW. 2005. Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem. 12(12):1395–1411.
   PubMed Web of Science ®Google Scholar
• 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(20):5432–5435.
   PubMed Web of Science ®Google Scholar
• 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(18):4110–4113.
   PubMed Web of Science ®Google Scholar
• Huffman JW, Zengin G, Wu M-J, Lu J, Hynd G, Bushell K, Thompson ALS, Bushell S, Tartal C, Hurst DP, et al. 2005. 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(1):89–112.
   PubMed Web of Science ®Google Scholar
• Hutter M, Broecker S, Kneisel S, Auwärter V. 2012. 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(1):54–65.
   PubMed Web of Science ®Google Scholar
• Hutter M, Moosmann B, Kneisel S, Auwarter V. 2013. Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism. J Mass Spectrom. 48(7):885–894.
   PubMed Web of Science ®Google Scholar
• Iversen L. 2018. The science of marijuana. New York: Oxford University Press.
   Google Scholar
• Jang M, Kim IS, Park YN, Kim J, Han I, Baeck S, Yang W, Yoo HH. 2016. Determination of urinary metabolites of XLR-11 by liquid chromatography-quadrupole time-of-flight mass spectrometry. Anal Bioanal Chem. 408(2):503–516.
   PubMed Web of Science ®Google Scholar
• John CA. 2012. Synthetic cannabinoids as drugs of abuse. Curr Drug Abuse Rev. 5(2):158–168.
   PubMedGoogle Scholar
• Kacinko SL, Xu A, Homan JW, McMullin MM, Warrington DM, Logan BK. 2011. Development and validation of a liquid chromatography-tandem mass spectrometry method for the identification and quantification of JWH-018, JWH-073, JWH-019, and JWH-250 in human whole blood. J Anal Toxicol. 35(7):386–393.
   PubMed Web of Science ®Google Scholar
• Kanamori T, Kanda K, Yamamuro T, Kuwayama K, Tsujikawa K, Iwata YT, Inoue H. 2015. Detection of main metabolites of XLR-11 and its thermal degradation product in human hepatoma HepaRG cells and human urine. Drug Test Anal. 7(4):341–345.
   PubMed Web of Science ®Google Scholar
• Karinen R, Tuv SS, Øiestad EL, Vindenes V. 2015. Concentrations of APINACA, 5F-APINACA, UR-144 and its degradant product in blood samples from six impaired drivers compared to previous reported concentrations of other synthetic cannabinoids. Forensic Sci Int. 246:98–103.
   PubMed Web of Science ®Google Scholar
• Kavanagh P, Grigoryev A, Melnik A, Savchuk S, Simonov A, Rozhanets V. 2013. Detection and tentative identification of urinary phase I metabolites of phenylacetylindole cannabimimetics JWH-203 and JWH-251, by GC-MS and LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 934:102–108.
   PubMed Web of Science ®Google Scholar
• 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(8):683–692.
   PubMed Web of Science ®Google Scholar
• Kneisel S, Speck M, Moosmann B, Corneillie TM, Butlin NG, Auwarter V. 2013. LC/ESI-MS/MS method for quantification of 28 synthetic cannabinoids in neat oral fluid and its application to preliminary studies on their detection windows. Anal Bioanal Chem. 405(14):4691–4706.
   PubMed Web of Science ®Google Scholar
• Knittel JL, Holler JM, Chmiel JD, Vorce SP, Magluilo J, Jr, Levine B, Ramos G, Bosy TZ. 2016. Analysis of parent synthetic cannabinoids in blood and urinary metabolites by liquid chromatography tandem mass spectrometry. J Anal Toxicol. 40(3):173–186.
   PubMed Web of Science ®Google Scholar
• Kong TY, Kim J-H, Kim DK, Lee HS. 2018. Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes. Arch Pharm Res. 41(7):691–710.
   PubMed Web of Science ®Google Scholar
• Lafaye G, Karila L, Blecha L, Benyamina A. 2017. Cannabis, cannabinoids, and health. Dialogues Clin Neurosci. 19(3):309–316.
   PubMed Web of Science ®Google Scholar
• Lam RPK, Tang MHY, Leung SC, Chong YK, Tsui MSH, Mak T. 2017. Supraventricular tachycardia and acute confusion following ingestion of e-cigarette fluid containing AB-FUBINACA and ADB-FUBINACA: a case report with quantitative analysis of serum drug concentrations. Clin Toxicol (Phila). 55(7):662–667.
   PubMed Web of Science ®Google Scholar
• Lambert DM. 2009. Cannabinoids in nature and medicine. Weinheim: Wiley–VCH.
   Google Scholar
• Lefever TW, Marusich JA, Thomas BF, Barrus DG, Peiper NC, Kevin RC, Wiley JL. 2017. Vaping synthetic cannabinoids: a novel preclinical model of E-cigarette use in mice. Subst Abuse. 11:1178221817701739–1178221817701739.
   Web of Science ®Google Scholar
• Livny A, Cohen K, Tik N, Tsarfaty G, Rosca P, Weinstein A. 2018. The effects of synthetic cannabinoids (SCs) on brain structure and function. Eur Neuropsychopharmacol. 28(9):1047–1057.
   PubMed Web of Science ®Google Scholar
• Lu HC, Mackie K. 2016. An introduction to the endogenous cannabinoid system. Biol Psychiatry. 79(7):516–525.
   PubMed Web of Science ®Google Scholar
• Malfitano AM, Basu S, Maresz K, Bifulco M, Dittel BN. 2014. What we know and do not know about the cannabinoid receptor 2 (CB2). Semin Immunol. 26(5):369–379.
   PubMed Web of Science ®Google Scholar
• Mander L, Liu HW. 2010. Comprehensive natural products II: chemistry and biology. Oxford, UK: Elsevier Science.
   Google Scholar
• Manera C, Arena C, Chicca A. 2016. Synthetic cannabinoid receptor agonists and antagonists: implication in CNS disorders. Recent Pat CNS Drug Discov. 10(2):142–156.
   PubMedGoogle Scholar
• Manseau MW. 2016a. Chapter 7, Synthetic cannabinoids - emergence, epidemiology, clinical effects, and management. In: Compton MT, editor. Marijuana and mental health. Arlington, VA: American Psychiatric Publishing; p. 149–169.
   Google Scholar
• Manseau MW. 2016b. Chapter 7, Synthetic cannabinoids: emergence, epidemiology, clinical effects and management. In: Compton MT, editor. Marijuana and mental health. Arlington, VA: American Psychiatric Publishing.
   Google Scholar
• Manseau MW. 2016c. Chapter 7, Synthetic cannabinoids: emergence, epidemiology, clinical effects, and management. In: Compton MT, editor. Marijuana and mental health. Arlington, VA: American Psychiatric Publishing; p. 272.
   Google Scholar
• Maroon J, Bost J. 2018. Review of the neurological benefits of phytocannabinoids. Surg Neurol Int. 9:91–91.
   PubMedGoogle Scholar
• Marusich JA, Wiley JL, Lefever TW, Patel PR, Thomas BF. 2018. Finding order in chemical chaos - continuing characterization of synthetic cannabinoid receptor agonists. Neuropharmacology. 134(Pt A):73–81.
   PubMed Web of Science ®Google Scholar
• Maurer H, Brandt SD, Nature S. 2018. New psychoactive substances: pharmacology, clinical, forensic and analytical toxicology. Switzerland: Springer International Publishing.
   Google Scholar
• Messina F, Rosati O, Curini M, Marcotullio MC. 2015. Chapter 2 - cannabis and bioactive cannabinoids. In: Atta Ur R, editor. Studies in natural product chemistry. Oxford, UK: Elsevier; p. 17–57.
   Google Scholar
• Meyer MR. 2016. New psychoactive substances: an overview on recent publications on their toxicodynamics and toxicokinetics. Arch Toxicol. 90(10):2421–2444.
   PubMed Web of Science ®Google Scholar
• Miliano C, Serpelloni G, Rimondo C, Mereu M, Marti MD, Luca MA. 2016. Neuropharmacology of new psychoactive substances (NPS): focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants. Front Neurosci. 10:1–21.
   PubMed Web of Science ®Google Scholar
• Mills B, Yepes A, Nugent K. 2015. Synthetic cannabinoids. Am J Med Sci. 350(1):59–62.
   PubMed Web of Science ®Google Scholar
• Moeller S, Lucke C, Struffert T, Schwarze B, Gerner ST, Schwab S, Kohrmann M, Machold K, Philipsen A, Muller HH. 2017. Ischemic stroke associated with the use of a synthetic cannabinoid (spice). Asian J Psychiatr. 25:127–130.
   PubMed Web of Science ®Google Scholar
• Montesano C, Vannutelli G, Piccirilli V, Sergi M, Compagnone D, Curini R. 2017. Application of a rapid μ-SPE clean-up for multiclass quantitative analysis of sixteen new psychoactive substances in whole blood by LC-MS/MS. Talanta. 167:260–267.
   PubMed Web of Science ®Google Scholar
• Moran CL, Le VH, Chimalakonda KC, Smedley AL, Lackey FD, Owen SN, Kennedy PD, Endres GW, Ciske FL, Kramer JB, et al. 2011. Quantitative measurement of JWH-018 and JWH-073 metabolites excreted in human urine. Anal Chem. 83(11):4228–4236.
   PubMed Web of Science ®Google Scholar
• Moritz E, Austin C, Wahl M, DesLauriers C, Navon L, Walblay K, Hendrickson M, Phillips A, Kerins J, Pennington AF, et al. 2018. Notes from the field: outbreak of severe illness linked to the vitamin K antagonist brodifacoum and use of synthetic cannabinoids - Illinois, March-April 2018. MMWR Morb Mortal Wkly Rep. 67(21):607–608.
   PubMed Web of Science ®Google Scholar
• Musah RA, Domin MA, Cody RB, Lesiak AD, John Dane A, Shepard J. 2012. Direct analysis in real time mass spectrometry with collision-induced dissociation for structural analysis of synthetic cannabinoids. Rapid Commun Mass Spectrom. 26(19):2335–2342.
   PubMed Web of Science ®Google Scholar
• Musah RA, Domin MA, Walling MA, Shepard J. 2012. Rapid identification of synthetic cannabinoids in herbal samples via direct analysis in real time mass spectrometry. Rapid Commun Mass Spectrom. 26(9):1109–1114.
   PubMed Web of Science ®Google Scholar
• Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. 2009. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 1(7):1333–1349.
   PubMed Web of Science ®Google Scholar
• Nakajima J, Takahashi M, Nonaka R, Seto T, Suzuki J, Yoshida M, Kanai C, Hamano T. 2011. Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the Internet and their cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays [journal article]. Forensic Toxicol. 29(2):132–141.
   Web of Science ®Google Scholar
• Niaz K, Khan F, Maqbool F, Momtaz SI, Hassan F, Nobakht-Haghighi N, Rahimifard M, Abdollahi M. 2017. Endo-cannabinoids system and the toxicity of cannabinoids with a biotechnological approach. Excli J. 16:688–711.
   PubMed Web of Science ®Google Scholar
• Nicolussi S, Gertsch J. 2015. Endocannabinoid transport revisited. Vitam Horm. 98:441–485.
   PubMed Web of Science ®Google Scholar
• Nielsen LM, Holm NB, Olsen L, Linnet K. 2016. Cytochrome P450-mediated metabolism of the synthetic cannabinoids UR-144 and XLR-11. Drug Test Anal. 8(8):792–800.
   PubMed Web of Science ®Google Scholar
• Obafemi AI, Kleinschmidt K, Goto C, Fout D. 2015. Cluster of acute toxicity from ingestion of synthetic cannabinoid-laced brownies. J Med Toxicol. 11(4):426–429.
   PubMed Web of Science ®Google Scholar
• Palamar JJ, Acosta P. 2015. Synthetic cannabinoid use in a nationally representative sample of US high school seniors. Drug Alcohol Depend. 149:194–202.
   PubMed Web of Science ®Google Scholar
• Palamar JJ, Barratt MJ, Coney L, Martins SS. 2017. Synthetic cannabinoid use among high school seniors. Pediatrics. 140(4):e20171330.
   PubMed Web of Science ®Google Scholar
• Papaseit E, Pérez-Mañá C, Pérez-Acevedo AP, Hladun O, Torres-Moreno MC, Muga R, Torrens M, Farré M. 2018. Cannabinoids: from pot to lab. Int J Med Sci. 15(12):1286–1295.
   PubMed Web of Science ®Google Scholar
• Parker LA. 2017. Cannabinoids and the brain. Cambridge: MIT Press.
   Google Scholar
• Patton AL, Chimalakonda KC, Moran CL, McCain KR, Radominska-Pandya A, James LP, Kokes C, Moran JH. 2013. K2 toxicity: fatal case of psychiatric complications following AM2201 exposure. J Forensic Sci. 58(6):1676–1680.
   PubMed Web of Science ®Google Scholar
• Patton AL, Seely KA, Chimalakonda KC, Tran JP, Trass M, Miranda A, Fantegrossi WE, Kennedy PD, Dobrowolski P, Radominska-Pandya A, et al. 2013. Targeted metabolomic approach for assessing human synthetic cannabinoid exposure and pharmacology. Anal Chem. 85(19):9390–9399.
   PubMed Web of Science ®Google Scholar
• Patton AL, Seely KA, Yarbrough AL, Fantegrossi W, James LP, McCain KR, Fujiwara R, Prather PL, Moran JH, Radominska-Pandya A. 2018. Altered metabolism of synthetic cannabinoid JWH-018 by human cytochrome P450 2C9 and variants. Biochem Biophys Res Commun. 498(3):597–602.
   PubMed Web of Science ®Google Scholar
• Pertwee RG. 2006. Cannabinoids. Vol. 168. Germany: Springer Science & Business Media. (Handb Exp Pharmacol.
   Google Scholar
• Phillips J, Lim F, Hsu R. 2017. The emerging threat of synthetic cannabinoids. Nurs Manage. 48(3):22–30.
   PubMedGoogle Scholar
• Preedy VR. 2016a. Handbook of cannabis and related pathologies: biology, pharmacology, diagnosis, and treatment. London: Elsevier Science.
   Google Scholar
• Preedy VR. 2016b. Neuropathology of drug addictions and substance misuse volume 1: foundations of understanding, tobacco, alcohol, cannabinoids and opioids. London: Elsevier Science.
   Google Scholar
• Presley B, Varnum S, Logan B. 2013. Analysis of synthetic cannabinoids in botanical material. A review of analytical methods and findings. Forensic Sci Rev. 25(1–2):27–46.
   Google Scholar
• Riederer AM, Campleman SL, Carlson RG, Boyer EW, Manini AF, Wax PM, Brent JA, Toxicology Investigators C. 2016. Acute poisonings from synthetic cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010–2015. MMWR Morb Mortal Wkly Rep. 65(27):692–695.
   PubMed Web of Science ®Google Scholar
• Robinson L, Goonawardena AV, Pertwee RG, Hampson RE, Riedel G. 2007. The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses hippocampal firing rate in rats. Br J Pharmacol. 151(5):688–700.
   PubMed Web of Science ®Google Scholar
• Sacco LN, Finklea K. 2016. Synthetic drugs: overview and issues for congress. Congressional Research Service. [accessed 2019 Jun 19]. https://www.everycrsreport.com/reports/R42066.html#_Toc450055245.
   Google Scholar
• Salomone A. 2015. Chapter 11 - Detection of new psychoactive substances. In: Kintz P, Salomone A, Vincenti M, editors. Hair analysis in clinical and forensic toxicology. Boston: Academic Press; p. 301–336.
   Google Scholar
• SAMHSA. 2012. The DAWN report: drug-related emergency department visits involving synthetic cannabinoids. substance abuse and mental health services administration. Center for Behavioral Health Statistics and Quality. [accessed 2019 May 8]. https://www.samhsa.gov/data/sites/default/files/DAWN105/DAWN105/SR105-synthetic-marijuana.pdf.
   Google Scholar
• Sanders AN, Stogner JM. 2016. Chapter 6, a profile of synthetic cannabinoid users. In: Preedy VR, editor. Handbook of cannabis and related pathologies: biology, pharmacology, diagnosis, and treatment. London, UK: Elsevier Science; p. 53–60.
   Google Scholar
• Schaefer N, Kettner M, Laschke MW, Schlote J, Ewald AH, Menger MD, Maurer HH, Schmidt PH. 2017. Distribution of synthetic cannabinoids JWH-210, RCS-4 and Δ 9-tetrahydrocannabinol after intravenous administration to pigs. Curr Neuropharmacol. 15(5):713–723.
   PubMed Web of Science ®Google Scholar
• Schoeder CT, Hess C, Madea B, Meiler J, Müller CE. 2018. Pharmacological evaluation of new constituents of “Spice”: synthetic cannabinoids based on indole, indazole, benzimidazole and carbazole scaffolds. Forensic Toxicol. 36(2):385–403.
   PubMed Web of Science ®Google Scholar
• Scourfield A, Flick C, Ross J, Wood DM, Thurtle N, Stellmach D, Dargan PI. 2019. Synthetic cannabinoid availability on darknet drug markets—changes during 2016–2017. Toxicol Commun. 3(1):7–15.
   Google Scholar
• Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL. 2012. AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: implications for opioid/cannabinoid interaction studies. Neuropharmacology. 63(5):905–915.
   PubMed Web of Science ®Google Scholar
• Seyit M, Ozen M, Oskay A, Kadioglu E. 2016. Effectiveness of the synthetic cannabinoids seminar. Turk J Emerg Med. 16(2):57–59.
   PubMed Web of Science ®Google Scholar
• 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(3):145–152.
   PubMed Web of Science ®Google Scholar
• Shevyrin V, Melkozerov V, Endres GW, Shafran Y, Morzherin Y. 2016. On a new cannabinoid classification system: a sight on the illegal market of novel psychoactive substances. Cannabis Cannabinoid Res. 1(1):186–194.
   Google Scholar
• Shevyrin VA, Morzherin YY. 2015. Cannabinoids: structures, effects, and classification [journal article. Russ Chem Bull. 64(6):1249–1266.
   Web of Science ®Google Scholar
• Shim JY, Welsh WJ, Howlett AC. 2003. Homology model of the CB1 cannabinoid receptor: sites critical for nonclassical cannabinoid agonist interaction. Biopolymers. 71(2):169–189.
   PubMed Web of Science ®Google Scholar
• Shivangi Bajpai AS. 2016. Cannabis sativa: therapeutic chemistry and classification. RRJPA. 5(3):126–135.
   Google Scholar
• Sim J, Cho HS, Lee J, In S, Kim E. 2017. Determination of AB-CHMINACA and its metabolites in human hair and their deposition in hair of abusers. J Pharm Biomed Anal. 140:162–168.
   PubMed Web of Science ®Google Scholar
• Sobolevsky T, Prasolov I, Rodchenkov G. 2010. Detection of JWH-018 metabolites in smoking mixture post-administration urine. Forensic Sci Int. 200(1-3):141–147.
   PubMed Web of Science ®Google Scholar
• Sobolevsky T, Prasolov I, Rodchenkov G. 2015. Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue. Drug Test Anal. 7(2):131–142.
   PubMed Web of Science ®Google Scholar
• Spaderna M, Addy PH, D'Souza DC. 2013. Spicing things up: synthetic cannabinoids. Psychopharmacology (Berl).). 228(4):525–540.
   PubMed Web of Science ®Google Scholar
• Strano-Rossi S, Anzillotti L, Dragoni S, Pellegrino RM, Goracci L, Pascali VL, Cruciani G. 2014. Metabolism of JWH-015, JWH-098, JWH-251, and JWH-307 in silico and in vitro: a pilot study for the detection of unknown synthetic cannabinoids metabolites. Anal Bioanal Chem. 406(15):3621–3636.
   PubMed Web of Science ®Google Scholar
• Synthetic Cannabonoid Data. 2019. American Association of Poison Control Centers. [accessed 2019 Aug 7]. https://www.aapcc.org/track/synthetic-cannabinoids.
   Google Scholar
• Tai S, Fantegrossi WE. 2014. Synthetic cannabinoids: pharmacology, behavioral effects, and abuse potential. Curr Addict Rep. 1(2):129–136.
   PubMedGoogle Scholar
• Tai S, Fantegrossi WE. 2017. Pharmacological and toxicological effects of synthetic cannabinoids and their metabolites. Curr Top Behav Neurosci. 32:249–262.
   PubMedGoogle Scholar
• Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. 2016. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol (Phila). 54(1):1–13.
   PubMed Web of Science ®Google Scholar
• Tarzia G, Duranti A, Tontini A, Spadoni G, Mor M, Rivara S, Vincenzo Plazzi P, Kathuria S, Piomelli D. 2003. Synthesis and structure-activity relationships of a series of pyrrole cannabinoid receptor agonists. Bioorg Med Chem. 11(18):3965–3973.
   PubMed Web of Science ®Google Scholar
• 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(27):2659–2663.
   PubMed Web of Science ®Google Scholar
• Tettey JN, Levissianos S. 2017. The global emergence of NPS: an analysis of a new drug trend. In: Corazza O, Roman-Urrestarazu A, editors. Novel psychoactive substances: policy, economics and drug regulation. Cham: Springer International Publishing; p. 1–12.
   Google Scholar
• Thomas BF, ElSohly M. 2015. The analytical chemistry of cannabis: quality assessment. Assurance, and regulation of medicinal Marijuana and cannabinoid preparations. UK: Elsevier Science.
   Google Scholar
• Toennes SW, Geraths A, Pogoda W, Paulke A, Wunder C, Theunissen EL, Ramaekers JG. 2017. Pharmacokinetic properties of the synthetic cannabinoid JWH-018 and of its metabolites in serum after inhalation. J Pharm Biomed Anal. 140:215–222.
   PubMed Web of Science ®Google Scholar
• Tournebize J, Gibaja V, Kahn JP. 2017. Acute effects of synthetic cannabinoids: Update 2015. Subst Abus. 38(3):344–366.
   PubMed Web of Science ®Google Scholar
• United States Drug Enforcement Administration (DEA). 2019. Controlled substances - alphabetical order. [accessed 2019 Jul 15]. https://www.dea.gov/drug-scheduling.
   Google Scholar
• UNODC. 2011. Synthetic cannabinoids in herbal products. [accessed 2019 Mar 10]. https://www.unodc.org/documents/scientific/Synthetic_Cannabinoids.pdf.
   Google Scholar
• UNODC. 2013. Recommended methods for the Identification and Analysis of Synthetic Cannabinoid Receptor Agonists in Seized Materials. United Nations. [accessed 2019 Apr 16]. https://www.unodc.org/unodc/en/scientists/recommended-methods-for-the-identification-and-analysis-of-synthetic-cannabinoid-receptor-agonists-in-seized-materials.html.
   Google Scholar
• UNODC. 2020. Current NPS threats Volume II. United Nations. [accessed 2020 Mar 3]. https://www.unodc.org/documents/scientific/Current_NPS_Threats_Volume_II_Web.pdf.
   Google Scholar
• van Amsterdam J, Brunt T, van den Brink W. 2015. The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects. J Psychopharmacol (Oxford)). 29(3):254–263.
   PubMed Web of Science ®Google Scholar
• Verty ANA, Stefanidis A, McAinch AJ, Hryciw DH, Oldfield B. 2015. Anti-obesity effect of the CB2 receptor agonist JWH-015 in diet-induced obese mice. PloS One. 10(11):e0140592– 19.
   PubMed Web of Science ®Google Scholar
• Wang M, Wang Y-H, Avula B, Radwan MM, Wanas AS, Mehmedic Z, van Antwerp J, ElSohly MA, Khan IA. 2017. Quantitative determination of cannabinoids in cannabis and cannabis products using ultra-high-performance supercritical fluid chromatography and diode array. J Forensic Sci. 62(3):602–611.
   PubMed Web of Science ®Google Scholar
• Waugh J, Najafi J, Hawkins L, Hill SL, Eddleston M, Vale JA, Thompson JP, Thomas S. 2016. Epidemiology and clinical features of toxicity following recreational use of synthetic cannabinoid receptor agonists: a report from the United Kingdom National Poisons Information Service. Clin Toxicol. 54(6):512–518.
   PubMed Web of Science ®Google Scholar
• WHO. 2016. World Health Organization. Management of substance abuse: cannabis. [accessed 2020 Mar 3]. https://www.who.int/substance_abuse/facts/cannabis/en.2016.
   Google Scholar
• Wiley JL, Marusich JA, Huffman JW, Balster RL, Thomas BF. 2011. Hijacking of basic research: the case of synthetic cannabinoids. Methods report (RTI Press). doi:10.3768/rtipress.2011.op.0007.1111.
   Google Scholar
• Wiley JL, Marusich JA, Lefever TW, Antonazzo KR, Wallgren MT, Cortes RA, Patel PR, Grabenauer M, Moore KN, Thomas BF. 2015. AB-CHMINACA, AB-PINACA, and FUBIMINA: affinity and potency of novel synthetic cannabinoids in producing δ9-tetrahydrocannabinol-like effects in mice. J Pharmacol Exp Ther. 354(3):328–339.
   PubMed Web of Science ®Google Scholar
• Wurita A, Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Suzuki O, Watanabe K. 2016. Identification and quantification of metabolites of AB-CHMINACA in a urine specimen of an abuser. Leg Med (Tokyo)). 19:113–118.
   PubMed Web of Science ®Google Scholar
• Zawilska JB, Wojcieszak J. 2014. Spice/K2 drugs-more than innocent substitutes for marijuana. Int J Neuropsychopharmacol. 17(3):509–525.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Ma P, Cole R, Wang G. 2006. Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS. Anal Bioanal Chem. 386(5):1345–1355.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Ma P, Iszard M, Cole RB, Wang W, Wang G. 2002. In vitro metabolism of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate, a Cannabinoid Receptor Agonist. Drug Metab Dispos. 30(10):1077–1086.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Ma P, Wang W, Cole RB, Wang G. 2004. Characterization of rat liver microsomal metabolites of AM-630, a potent cannabinoid receptor antagonist, by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. J Mass Spectrom. 39(6):672–681.
   PubMed Web of Science ®Google Scholar
• 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(27):464–467.
   PubMed Web of Science ®Google Scholar
• Zou S, Kumar U. 2018. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 19(3):833.
   PubMed Web of Science ®Google Scholar