Fatal Poisonings Associated with New Psychoactive Substances

  • Robert KronstrandEmail author
  • Davide Guerrieri
  • Svante Vikingsson
  • Ariane Wohlfarth
  • Henrik Gréen
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 252)


This chapter describes how new psychoactive substances (NPS) have been involved in fatal intoxications from 2010 and onwards. It summarizes the circumstances, antemortem symptoms, and adverse effects that have led to death after ingestion of one or more NPS and tabulates concentrations, and postmortem findings from these intoxications.

Consumption of NPS exerts health problems and unknown risks for the users. Data on toxicity of many NPS are scarce or nonexistent and long-term toxicity and risks are still largely unknown. In addition, purity and composition of products containing NPS are often inconsistent or not known, which places users at high risk as evidenced by hospital emergency admissions and deaths.

The most serious threat to drug users are the synthetic opioids that with strong central nervous depressant effects have caused numerous accidental deaths spread over the entire globe. The synthetic cannabinoids seem to be the most unpredictable with no clear toxidrome and unknown or poorly understood mechanisms of toxicity, but with adverse effects pointing toward the cardiovascular system. The toxidromes commonly encountered after ingestion of cathinones and phenethylamines are of sympathomimetic and hallucinogenic character, which includes risk of developing a serotonin syndrome, excited delirium, and life-threatening cardiovascular effects. In comparison to their conventional “parent” drug, i.e., heroin, cannabis, and amphetamine, most NPS appear to exhibit more severe adverse effects. The deaths attributed to NPS have dramatically increased in the last years. In our opinion, this is because of the shift from synthetic cannabinoids and cathinones to the even more toxic and dangerously potent fentanyl analogues.


Cathinones Death Designer drugs Fatal intoxications New psychoactive substances Opioids Phenethylamines Postmortem concentrations Synthetic cannabinoids 


  1. Adamowicz P (2016) Fatal intoxication with synthetic cannabinoid MDMB-CHMICA. Forensic Sci Int 261:e5–10PubMedGoogle Scholar
  2. Adamowicz P, Tokarczyk B, Stanaszek R, Slopianka M (2013) Fatal mephedrone intoxication – a case report. J Anal Toxicol 37:37–42PubMedGoogle Scholar
  3. Adamowicz P, Zuba D (2015) Fatal intoxication with methoxetamine. J Forensic Sci 60(Suppl 1):S264–S268PubMedGoogle Scholar
  4. Adamowicz P, Zuba D, Byrska B (2014) Fatal intoxication with 3-methyl-N-methylcathinone (3-MMC) and 5-(2-aminopropyl)benzofuran (5-APB). Forensic Sci Int 245:126–132PubMedGoogle Scholar
  5. Adebamiro A, Perazella MA (2012) Recurrent acute kidney injury following bath salts intoxication. Am J Kidney Dis 59:273–275PubMedGoogle Scholar
  6. Alper RH (1990) Hemodynamic and renin responses to (+−)-DOI, a selective 5-HT2 receptor agonist, in conscious rats. Eur J Pharmacol 175:323–332PubMedGoogle Scholar
  7. Andreasen MF, Telving R, Rosendal I, Eg MB, Hasselstrom JB, Andersen LV (2015) A fatal poisoning involving 25C-NBOMe. Forensic Sci Int 251:e1–e8PubMedGoogle Scholar
  8. Angerer V, Franz F, Schwarze B, Moosmann B, Auwarter V (2016) Reply to “sudden cardiac death following use of the synthetic cannabinoid MDMB-CHMICA”. J Anal Toxicol 40:240–242PubMedPubMedCentralGoogle Scholar
  9. Angerer V, Jacobi S, Franz F, Auwarter V, Pietsch J (2017) Three fatalities associated with the synthetic cannabinoids 5F-ADB, 5F-PB-22, and AB-CHMINACA. Forensic Sci Int 281:e9–e15PubMedGoogle Scholar
  10. Armenian P, Olson A, Anaya A, Kurtz A, Ruegner R, Gerona RR (2017) Fentanyl and a novel synthetic opioid U-47700 masquerading as street “Norco” in Central California: a case report. Ann Emerg Med 69:87–90PubMedGoogle Scholar
  11. Aromatario M, Bottoni E, Santoni M, Ciallella C (2012) New “lethal highs”: a case of a deadly cocktail of GHB and mephedrone. Forensic Sci Int 223:e38–e41PubMedGoogle Scholar
  12. Bachs L, Morland H (2001) Acute cardiovascular fatalities following cannabis use. Forensic Sci Int 124:200–203PubMedGoogle Scholar
  13. Bäckberg M, Beck O, Hulten P, Rosengren-Holmberg J, Helander A (2014) Intoxications of the new psychoactive substance 5-(2-aminopropyl)indole (5-IT): a case series from the Swedish STRIDA project. Clin Toxicol (Phila) 52:618–624Google Scholar
  14. Barrios L, Grison-Hernando H, Boels D, Bouquie R, Monteil-Ganiere C, Clement R (2016) Death following ingestion of methylone. Int J Leg Med 130:381–385Google Scholar
  15. Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB (2005) N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or “Ecstasy”). Neuropsychopharmacology 30:550–560PubMedGoogle Scholar
  16. Behonick G, Shanks KG, Firchau DJ, Mathur G, Lynch CF, Nashelsky M, Jaskierny DJ, Meroueh C (2014) Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22. J Anal Toxicol 38:559–562PubMedPubMedCentralGoogle Scholar
  17. Bersani FS, Corazza O, Albano G, Valeriani G, Santacroce R, Bolzan Mariotti Posocco F, Cinosi E, Simonato P, Martinotti G, Bersani G, Schifano F (2014) 25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug. Biomed Res Int 2014:734749PubMedPubMedCentralGoogle Scholar
  18. Bishop-Freeman SC, Feaster MS, Beal J, Miller A, Hargrove RL, Brower JO, Winecker RE (2016) Loperamide-related deaths in North Carolina. J Anal Toxicol 40:677–686PubMedGoogle Scholar
  19. Borek HA, Holstege CP (2012) Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med 60:103–105PubMedGoogle Scholar
  20. Boulanger-Gobeil C, St-Onge M, Laliberte M, Auger PL (2012) Seizures and hyponatremia related to ethcathinone and methylone poisoning. J Med Toxicol 8:59–61PubMedGoogle Scholar
  21. Brittain RT, Kellett DN, Neat ML, Stables R (1973) Proceedings: anti-nociceptive effects in N-substituted cyclohexylmethylbenzamides. Br J Pharmacol 49:158P–159PPubMedPubMedCentralGoogle Scholar
  22. Butler DC, Shanks K, Behonick GS, Smith D, Presnell SE, Tormos LM (2017) Three cases of fatal acrylfentanyl toxicity in the United States and a review of literature. J Anal Toxicol 42:e6–e11Google Scholar
  23. Callaghan PD, Irvine RJ, Daws LC (2005) Differences in the in vivo dynamics of neurotransmitter release and serotonin uptake after acute para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine revealed by chronoamperometry. Neurochem Int 47:350–361PubMedGoogle Scholar
  24. Carbone PN, Carbone DL, Carstairs SD, Luzi SA (2013) Sudden cardiac death associated with methylone use. Am J Forensic Med Pathol 34:26–28PubMedGoogle Scholar
  25. Cawrse BM, Levine B, Jufer RA, Fowler DR, Vorce SP, Dickson AJ, Holler JM (2012) Distribution of methylone in four postmortem cases. J Anal Toxicol 36:434–439PubMedGoogle Scholar
  26. Chiappini S, Claridge H, Corkery JM, Goodair C, Loi B, Schifano F (2015) Methoxetamine-related deaths in the UK: an overview. Hum Psychopharmacol 30:244–248PubMedGoogle Scholar
  27. Coopman V, Blanckaert P, Van Parys G, Van Calenbergh S, Cordonnier J (2016a) A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700). Forensic Sci Int 266:68–72PubMedGoogle Scholar
  28. Coopman V, Cordonnier J, De Leeuw M, Cirimele V (2016b) Ocfentanil overdose fatality in the recreational drug scene. Forensic Sci Int 266:469–473PubMedGoogle Scholar
  29. Cosbey SH, Peters KL, Quinn A, Bentley A (2013) Mephedrone (methylmethcathinone) in toxicology casework: a Northern Ireland perspective. J Anal Toxicol 37:74–82PubMedGoogle Scholar
  30. Cunningham SM, Haikal NA, Kraner JC (2016) Fatal intoxication with acetyl fentanyl. J Forensic Sci 61(Suppl 1):S276–S280PubMedGoogle Scholar
  31. DailyMed (2014) Naloxone hydrochloride injection, solution. US National Library of MedicineGoogle Scholar
  32. Daniulaityte R, Juhascik MP, Strayer KE, Sizemore IE, Harshbarger KE, Antonides HM, Carlson RR (2017) Overdose deaths related to fentanyl and its analogs – Ohio, January-February 2017. MMWR Morb Mortal Wkly Rep 66:904–908PubMedPubMedCentralGoogle Scholar
  33. Derungs A, Schietzel S, Meyer MR, Maurer HH, Krahenbuhl S, Liechti ME (2011) Sympathomimetic toxicity in a case of analytically confirmed recreational use of naphyrone (naphthylpyrovalerone). Clin Toxicol (Phila) 49:691–693Google Scholar
  34. Dines AM, Wood DM, Galicia M, Yates CM, Heyerdahl F, Hovda KE, Giraudon I, Sedefov R, Euro DENRG, Dargan PI (2015) Presentations to the emergency department following cannabis use – a multi-centre case series from ten European countries. J Med Toxicol 11:415–421PubMedPubMedCentralGoogle Scholar
  35. Dziadosz M, Klintschar M, Teske J (2017) Postmortem concentration distribution in fatal cases involving the synthetic opioid U-47700. Int J Leg Med 131(6):1555–1556Google Scholar
  36. ECDD (2014) AH-7921 Critical Review Report Agenda Item 4.21. 16 Feb 2018
  37. ECDD (2015) MT-45 Critical Review Report Agenda Item 5.1. 16 Feb 2018
  38. ECDD (2016) U-47700 Critical Review Report Agenda Item 4.1. 16 Feb 2018
  39. Eggleston W, Clark KH, Marraffa JM (2017) Loperamide abuse associated with cardiac dysrhythmia and death. Ann Emerg Med 69:83–86PubMedGoogle Scholar
  40. Eiden C, Cathala P, Mathieu-Daude JC, Marson B, Baccino E, Leglise Y, Peyriere H (2012) Methadone-related deaths in Montpellier and Region, from 2000 to 2010. Therapie 67:515–522PubMedGoogle Scholar
  41. Ellefsen KN, Taylor EA, Simmons P, Willoughby V, Hall BJ (2017) Multiple drug-toxicity involving novel psychoactive substances, 3-Fluorophenmetrazine and U-47700. J Anal Toxicol:1–6Google Scholar
  42. Elliott S (2011) Current awareness of piperazines: pharmacology and toxicology. Drug Test Anal 3:430–438PubMedGoogle Scholar
  43. Elliott S, Sedefov R, Evans-Brown M (2018) Assessing the toxicological significance of new psychoactive substances in fatalities. Drug Test Anal 10:120–126PubMedGoogle Scholar
  44. Elliott SP, Brandt SD, Smith C (2016) The first reported fatality associated with the synthetic opioid 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) and implications for forensic analysis. Drug Test Anal 8:875–879PubMedGoogle Scholar
  45. Elliott SP, Brandt SD, Wallach J, Morris H, Kavanagh PV (2015) First reported fatalities associated with the “research chemical” 2-methoxydiphenidine. J Anal Toxicol 39:287–293PubMedGoogle Scholar
  46. EMCDDA-Europol (2010) Joint Report on a new psychoactive substance: 4-methylmethcathinone (mephedrone). 16 Feb 2018
  47. EMCDDA-Europol (2012) 2011 Annual Report on the implementation of Council Decision 2005/387/JHA. 16 Feb 2018
  48. EMCDDA-Europol (2013) 2012 Annual Report on the implementation of Council Decision 2005/387/JHA (New Drugs in Europe). 16 Feb 2018
  49. EMCDDA–Europol (2009) 2008 Annual Report on the implementation of Council Decision 2005/387/JHA. 16 Feb 2018
  50. EMCDDA (2013a) Report on the risk assessment of 5-(2-aminopropyl)indole in the framework of the Council Decision on new psychoactive substances. 16 Feb 2018
  51. EMCDDA (2013b) Report on the risk assessment of 2-(3-methoxyphenyl)-2-(ethylamino) cyclohexanone (methoxetamine) in the framework of the Council Decision on new psychoactive substances. 16 Feb 2018
  52. EMCDDA (2015) Report on the risk assessment of 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-pyrrolidinovalerophenone, α-PVP) in the framework of the Council Decision on new psychoactive substances. 16 Feb 2018
  53. Fels H, Krueger J, Sachs H, Musshoff F, Graw M, Roider G, Stoever A (2017) Two fatalities associated with synthetic opioids: AH-7921 and MT-45. Forensic Sci Int 277:e30–e35PubMedGoogle Scholar
  54. Fort C, Curtis B, Nichols C, Niblo C (2016) Acetyl fentanyl toxicity: two case reports. J Anal Toxicol 40:754–757PubMedGoogle Scholar
  55. Garrett G, Sweeney M (2010) The serotonin syndrome as a result of mephedrone toxicity. BMJ Case Rep 2010Google Scholar
  56. Gerace E, Petrarulo M, Bison F, Salomone A, Vincenti M (2014) Toxicological findings in a fatal multidrug intoxication involving mephedrone. Forensic Sci Int 243:68–73PubMedGoogle Scholar
  57. Gieron J, Adamowicz P (2016) Fatal poisoning with the synthetic cannabinoid AB-CHMINACA and ethyl alcohol – a case study and literature review. Problems Forensic Sci 106:482–495Google Scholar
  58. Gil D, Adamowicz P, Skulska A, Tokarczyk B, Stanaszek R (2013) Analysis of 4-MEC in biological and non-biological material – three case reports. Forensic Sci Int 228:e11–e15PubMedGoogle Scholar
  59. Gray NM, Cheng BK (1989) 1,2-diarylethylamines for treatment of neurotoxic injury. SEARLE & CO (US)Google Scholar
  60. Guerrieri D, Rapp E, Roman M, Druid H, Kronstrand R (2017a) Postmortem and toxicological findings in a series of furanylfentanyl-related deaths. J Anal Toxicol 41:242–249PubMedGoogle Scholar
  61. Guerrieri D, Rapp E, Roman M, Thelander G, Kronstrand R (2017b) Acrylfentanyl: another new psychoactive drug with fatal consequences. Forensic Sci Int 277:e21–e29PubMedGoogle Scholar
  62. Halberstadt AL (2017) Pharmacology and toxicology of N-benzylphenethylamine (“NBOMe”) hallucinogens. Curr Top Behav Neurosci 32:283–311PubMedGoogle Scholar
  63. Hartung B, Kauferstein S, Ritz-Timme S, Daldrup T (2014) Sudden unexpected death under acute influence of cannabis. Forensic Sci Int 237:e11–e13PubMedGoogle Scholar
  64. Hasegawa K, Suzuki O, Wurita A, Minakata K, Yamagishi I, Nozawa H, Gonmori K, Watanabe K (2014a) Postmortem distribution of α-pyrrolidinovalerophenone and its metabolite in body fluids and solid tissues in a fatal poisoning case measured by LC–MS–MS with the standard addition method. Forensic Toxicol 32:225–234Google Scholar
  65. Hasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (2014b) Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicol 33:45–53Google Scholar
  66. Hasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (2015) Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicol 33:45–53Google Scholar
  67. Hayes AG, Tyers MB (1983) Determination of receptors that mediate opiate side effects in the mouse. Br J Pharmacol 79:731–736PubMedPubMedCentralGoogle Scholar
  68. Helander A, Backberg M, Signell P, Beck O (2017) Intoxications involving acrylfentanyl and other novel designer fentanyls – results from the Swedish STRIDA project. Clin Toxicol (Phila) 55:589–599Google Scholar
  69. Helander A, Beck O, Backberg M (2015) Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine. Clin Toxicol (Phila) 53:446–453Google Scholar
  70. Helland A, Brede WR, Michelsen LS, Gundersen POM, Aarset H, Skjolas JE, Slordal L (2017) Two hospitalizations and one death after exposure to ortho-fluorofentanyl. J Anal Toxicol 41:708–709PubMedGoogle Scholar
  71. Hess C, Stockhausen S, Kernbach-Wighton G, Madea B (2015) Death due to diabetic ketoacidosis: induction by the consumption of synthetic cannabinoids? Forensic Sci Int 257:e6–11PubMedGoogle Scholar
  72. Johansen SS, Hansen AC, Muller IB, Lundemose JB, Franzmann MB (2003) Three fatal cases of PMA and PMMA poisoning in Denmark. J Anal Toxicol 27:253–256PubMedGoogle Scholar
  73. Karinen R, Tuv SS, Rogde S, Peres MD, Johansen U, Frost J, Vindenes V, Oiestad AM (2014) Lethal poisonings with AH-7921 in combination with other substances. Forensic Sci Int 244:e21–e24PubMedGoogle Scholar
  74. Kasper AM, Ridpath AD, Arnold JK, Chatham-Stephens K, Morrison M, Olayinka O, Parker C, Galli R, Cox R, Preacely N, Anderson J, Kyle PB, Gerona R, Martin C, Schier J, Wolkin A, Dobbs T (2015) Severe illness associated with reported use of synthetic cannabinoids – Mississippi, April 2015. MMWR Morb Mortal Wkly Rep 64:1121–1122PubMedGoogle Scholar
  75. Katz KD, Leonetti AL, Bailey BC, Surmaitis RM, Eustice ER, Kacinko S, Wheatley SM (2016) Case series of synthetic cannabinoid intoxication from one toxicology center. West J Emerg Med 17:290–294PubMedPubMedCentralGoogle Scholar
  76. Kesha K, Boggs CL, Ripple MG, Allan CH, Levine B, Jufer-Phipps R, Doyon S, Chi P, Fowler DR (2013) Methylenedioxypyrovalerone (“bath salts”), related death: case report and review of the literature. J Forensic Sci 58:1654–1659PubMedGoogle Scholar
  77. Khademi H, Kamangar F, Brennan P, Malekzadeh R (2016) Opioid therapy and its side effects: a review. Arch Iran Med 19:870–876PubMedGoogle Scholar
  78. Kronstrand R, Roman M, Andersson M, Eklund A (2013a) Toxicological findings of synthetic cannabinoids in recreational users. J Anal Toxicol 37:534–541PubMedGoogle Scholar
  79. Kronstrand R, Roman M, Dahlgren M, Thelander G, Wikstrom M, Druid H (2013b) A cluster of deaths involving 5-(2-aminopropyl)indole (5-IT). J Anal Toxicol 37:542–546PubMedGoogle Scholar
  80. Kronstrand R, Thelander G, Lindstedt D, Roman M, Kugelberg FC (2014) Fatal intoxications associated with the designer opioid AH-7921. J Anal Toxicol 38:599–604PubMedGoogle Scholar
  81. Krotulski AJ, Papsun DM, Friscia M, Swartz JL, Holsey BD, Logan BK (2017) Fatality following ingestion of tetrahydrofuranylfentanyl, U-49900 and methoxy-phencyclidine. J Anal Toxicol:1–6Google Scholar
  82. Kudo K, Usumoto Y, Kikura-Hanajiri R, Sameshima N, Tsuji A, Ikeda N (2015) A fatal case of poisoning related to new cathinone designer drugs, 4-methoxy PV8, PV9, and 4-methoxy PV9, and a dissociative agent, diphenidine. Leg Med (Tokyo) 17:421–426Google Scholar
  83. Kueppers VB, Cooke CT (2015) 25I-NBOMe related death in Australia: a case report. Forensic Sci Int 249:e15–e18PubMedGoogle Scholar
  84. Kusano M, Zaitsu K, Taki K, Hisatsune K, Nakajima J, Moriyasu T, Asano T, Hayashi Y, Tsuchihashi H, Ishii A (2017) Fatal intoxication by 5F-ADB and diphenidine: detection, quantification, and investigation of their main metabolic pathways in humans by LC/MS/MS and LC/Q-TOFMS. Drug Test Anal 10:1–10PubMedGoogle Scholar
  85. Lasoff DR, Koh CH, Corbett B, Minns AB, Cantrell FL (2017) Loperamide trends in abuse and misuse over 13 years: 2002-2015. Pharmacotherapy 37:249–253PubMedGoogle Scholar
  86. Lin DL, Liu HC, Yin HL (2007) Recent paramethoxymethamphetamine (PMMA) deaths in Taiwan. J Anal Toxicol 31:109–113PubMedGoogle Scholar
  87. Lin JC, Jan RK, Lee H, Jensen MA, Kydd RR, Russell BR (2011) Determining the subjective and physiological effects of BZP combined with TFMPP in human males. Psychopharmacology (Berl) 214:761–768Google Scholar
  88. Loi B, Corkery JM, Claridge H, Goodair C, Chiappini S, Gimeno Clemente C, Schifano F (2015) Deaths of individuals aged 16-24 years in the UK after using mephedrone. Hum Psychopharmacol 30:225–232PubMedGoogle Scholar
  89. Lowe LM, Peterson BL, Couper FJ (2015) A case review of the first analytically confirmed 25I-NBOMe-related death in Washington state. J Anal Toxicol 39:668–671PubMedGoogle Scholar
  90. Luciano RL, Perazella MA (2014) Nephrotoxic effects of designer drugs: synthetic is not better! Nat Rev Nephrol 10:314–324PubMedGoogle Scholar
  91. Lurie Y, Gopher A, Lavon O, Almog S, Sulimani L, Bentur Y (2012) Severe paramethoxymethamphetamine (PMMA) and paramethoxyamphetamine (PMA) outbreak in Israel. Clin Toxicol (Phila) 50:39–43Google Scholar
  92. Lusthof KJ, Oosting R, Maes A, Verschraagen M, Dijkhuizen A, Sprong AG (2011) A case of extreme agitation and death after the use of mephedrone in the Netherlands. Forensic Sci Int 206:e93–e95PubMedGoogle Scholar
  93. Maeda H, Kikura-Hanajiri R, Kawamura M, Nagashima E, Yoshida KI (2017) AB-CHMINACA-induced sudden death from non-cardiogenic pulmonary edema. Clin Toxicol (Phila) 56:1–3PubMedGoogle Scholar
  94. Martin TL (2001) Three cases of fatal paramethoxyamphetamine overdose. J Anal Toxicol 25:649–651PubMedGoogle Scholar
  95. Martucci HFH, Ingle EA, Hunter MD, Rodda LN (2018) Distribution of furanyl fentanyl and 4-ANPP in an accidental acute death: a case report. Forensic Sci Int 283:e13–e17PubMedGoogle Scholar
  96. Mash DC, Duque L, Pablo J, Qin Y, Adi N, Hearn WL, Hyma BA, Karch SB, Druid H, Wetli CV (2009) Brain biomarkers for identifying excited delirium as a cause of sudden death. Forensic Sci Int 190:e13–e19PubMedGoogle Scholar
  97. Maskell PD, De Paoli G, Seneviratne C, Pounder DJ (2011) Mephedrone (4-methylmethcathinone)-related deaths. J Anal Toxicol 35:188–191PubMedGoogle Scholar
  98. McIntyre IM, Gary RD, Joseph S, Stabley R (2017) A fatality related to the synthetic opioid U-47700: postmortem concentration distribution. J Anal Toxicol 41:158–160PubMedGoogle Scholar
  99. McIntyre IM, Gary RD, Trochta A, Stolberg S, Stabley R (2015a) Acute 5-(2-aminopropyl)benzofuran (5-APB) intoxication and fatality: a case report with postmortem concentrations. J Anal Toxicol 39:156–159PubMedGoogle Scholar
  100. McIntyre IM, Hamm CE, Aldridge L, Nelson CL (2013) Acute methylone intoxication in an accidental drowning – a case report. Forensic Sci Int 231:e1–e3PubMedGoogle Scholar
  101. McIntyre IM, Trochta A, Gary RD, Malamatos M, Lucas JR (2015b) An acute acetyl fentanyl fatality: a case report with postmortem concentrations. J Anal Toxicol 39:490–494PubMedGoogle Scholar
  102. McIntyre IM, Trochta A, Gary RD, Wright J, Mena O (2016) An acute butyr-fentanyl fatality: a case report with postmortem concentrations. J Anal Toxicol 40:162–166PubMedGoogle Scholar
  103. Mercer SL, Coop A (2011) Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance. Curr Top Med Chem 11:1157–1164PubMedPubMedCentralGoogle Scholar
  104. Mofenson HC, Greensher J (1970) The nontoxic ingestion. Pediatr Clin North Am 17:583–590PubMedGoogle Scholar
  105. Mohr AL, Friscia M, Papsun D, Kacinko SL, Buzby D, Logan BK (2016) Analysis of novel synthetic opioids U-47700, U-50488 and furanyl fentanyl by LC-MS/MS in postmortem casework. J Anal Toxicol 40:709–717PubMedGoogle Scholar
  106. Mounteney J, Giraudon I, Denissov G, Griffiths P (2015) Fentanyls: are we missing the signs? Highly potent and on the rise in Europe. Int J Drug Policy 26:626–631PubMedGoogle Scholar
  107. Murray BL, Murphy CM, Beuhler MC (2012) Death following recreational use of designer drug “bath salts” containing 3,4-Methylenedioxypyrovalerone (MDPV). J Med Toxicol 8:69–75PubMedPubMedCentralGoogle Scholar
  108. Nagai H, Saka K, Nakajima M, Maeda H, Kuroda R, Igarashi A, Tsujimura-Ito T, Nara A, Komori M, Yoshida K (2014) Sudden death after sustained restraint following self-administration of the designer drug alpha-pyrrolidinovalerophenone. Int J Cardiol 172:263–265PubMedGoogle Scholar
  109. Nakamura H, Shimizu M (1976) Comparative study of 1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine and its enantiomorphs on analgesic and other pharmacological activities in experimental animals. Arch Int Pharmacodyn Ther 221:105–121PubMedGoogle Scholar
  110. O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM (2017) Deaths involving fentanyl, fentanyl analogs, and U-47700 – 10 states, July-December 2016. MMWR Morb Mortal Wkly Rep 66:1197–1202PubMedPubMedCentralGoogle Scholar
  111. 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 58:1676–1680PubMedPubMedCentralGoogle Scholar
  112. Paul ABM, Simms L, Amini S, Paul AE (2017) Teens and spice: a review of adolescent fatalities associated with synthetic cannabinoid use. J Forensic Sci. PubMedGoogle Scholar
  113. Pearson JM, Hargraves TL, Hair LS, Massucci CJ, Frazee CC 3rd, Garg U, Pietak BR (2012) Three fatal intoxications due to methylone. J Anal Toxicol 36:444–451PubMedGoogle Scholar
  114. Penders TM (2013) The syndrome of excited delirium following use of “bath salts”. J Clin Psychiatry 74:518PubMedGoogle Scholar
  115. Penders TM, Gestring R (2011) Hallucinatory delirium following use of MDPV: “Bath Salts”. Gen Hosp Psychiatry 33:525–526PubMedGoogle Scholar
  116. Penders TM, Gestring RE (2014) Letter to the editor – methylenedioxypyrovalerone as a cause of excited delirium. J Forensic Sci 59:869PubMedGoogle Scholar
  117. Penders TM, Gestring RE, Vilensky DA (2012a) Excited delirium following use of synthetic cathinones (bath salts). Gen Hosp Psychiatry 34:647–650PubMedGoogle Scholar
  118. Penders TM, Gestring RE, Vilensky DA (2012b) Intoxication delirium following use of synthetic cathinone derivatives. Am J Drug Alcohol Abuse 38:616–617PubMedGoogle Scholar
  119. Pereira J, Lawlor P, Vigano A, Dorgan M, Bruera E (2001) Equianalgesic dose ratios for opioids. A critical review and proposals for long-term dosing. J Pain Symptom Manage 22:672–687PubMedGoogle Scholar
  120. Poklis J, Poklis A, Wolf C, Hathaway C, Arbefeville E, Chrostowski L, Devers K, Hair L, Mainland M, Merves M, Pearson J (2016) Two fatal intoxications involving butyryl fentanyl. J Anal Toxicol 40:703–708PubMedPubMedCentralGoogle Scholar
  121. Poklis J, Poklis A, Wolf C, Mainland M, Hair L, Devers K, Chrostowski L, Arbefeville E, Merves M, Pearson J (2015) Postmortem tissue distribution of acetyl fentanyl, fentanyl and their respective nor-metabolites analyzed by ultrahigh performance liquid chromatography with tandem mass spectrometry. Forensic Sci Int 257:435–441PubMedPubMedCentralGoogle Scholar
  122. Poklis JL, Devers KG, Arbefeville EF, Pearson JM, Houston E, Poklis A (2014) Postmortem detection of 25I-NBOMe [2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death. Forensic Sci Int 234:e14–e20PubMedGoogle Scholar
  123. Potocka-Banas B, Janus T, Majdanik S, Banas T, Dembinska T, Borowiak K (2017) Fatal intoxication with alpha-PVP, a synthetic cathinone derivative. J Forensic Sci 62:553–556PubMedGoogle Scholar
  124. Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (2015) Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology 99:546–553PubMedGoogle Scholar
  125. Rohrig TP, Miller SA, Baird TR (2017) U-47700: a not so new opioid. J Anal Toxicol 42:e12–e14Google Scholar
  126. Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, Iversen L (2013) The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One 8:e59334PubMedPubMedCentralGoogle Scholar
  127. Saito T, Namera A, Miura N, Ohta S, Miyazaki S, Osawa M, Inokuchi S (2013) A fatal case of MAM-2201 poisoning. Forensic Toxicol 31:333–337Google Scholar
  128. Sasaki C, Saito T, Shinozuka T, Irie W, Murakami C, Maeda K, Nakamaru N, Oishi M, Nakamura S, Kurihara K (2015) A case of death caused by abuse of a synthetic cannabinoid N-1-naphthalenyl-1-pentyl-1H-indole-3-carboxamide. Forensic Toxicol 33:165–169Google Scholar
  129. Schaefer N, Peters B, Bregel D, Kneisel S, Auwaerter V, Schmidt PH, Ewald AH (2013) A fatal case involving several synthetic cannabinoids. Toxichem Krimtech:248–251Google Scholar
  130. Seetohul LN, Pounder DJ (2013) Four fatalities involving 5-IT. J Anal Toxicol 37:447–451PubMedGoogle Scholar
  131. Shanks KG, Behonick GS (2016) Death after use of the synthetic cannabinoid 5F-AMB. Forensic Sci Int 262:e21–e24PubMedGoogle Scholar
  132. Shanks KG, Behonick GS, Archuleta PA, Jaskierny DJ (2014) Case reports: fatalities associated with the synthetic cannabinoid AB-PINACA. In: Society of Forensic Toxicologists (SOFT) annual meeting abstract proceedings, Grand RapidsGoogle Scholar
  133. Shanks KG, Clark W, Behonick G (2016) Death associated with the use of the synthetic cannabinoid ADB-FUBINACA. J Anal Toxicol 40:236–239PubMedPubMedCentralGoogle Scholar
  134. 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 36:145–152PubMedGoogle Scholar
  135. Shanks KG, Sozio T, Behonick GS (2015a) Fatal intoxications with 25B-NBOMe and 25I-NBOMe in Indiana during 2014. J Anal Toxicol 39:602–606PubMedGoogle Scholar
  136. Shanks KG, Winston D, Heidingsfelder J, Behonick G (2015b) Case reports of synthetic cannabinoid XLR-11 associated fatalities. Forensic Sci Int 252:e6–e9PubMedGoogle Scholar
  137. Shoff EN, Zaney ME, Kahl JH, Hime GW, Boland DM (2017) Qualitative identification of fentanyl analogs and other opioids in postmortem cases by UHPLC-ion trap-MSn. J Anal Toxicol 41:484–492PubMedGoogle Scholar
  138. Simmler LD, Rickli A, Hoener MC, Liechti ME (2014) Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology 79:152–160PubMedGoogle Scholar
  139. Spiller HA, Ryan ML, Weston RG, Jansen J (2011) Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol (Phila) 49:499–505Google Scholar
  140. Swanson DM, Hair LS, Strauch Rivers SR, Smyth BC, Brogan SC, Ventoso AD, Vaccaro SL, Pearson JM (2017) Fatalities involving carfentanil and furanyl fentanyl: two case reports. J Anal Toxicol 41:498–502PubMedGoogle Scholar
  141. Swortwood MJ, Boland DM, DeCaprio AP (2013) Determination of 32 cathinone derivatives and other designer drugs in serum by comprehensive LC-QQQ-MS/MS analysis. Anal Bioanal Chem 405:1383–1397PubMedGoogle Scholar
  142. Sykutera M, Cychowska M, Bloch-Boguslawska E (2015) A fatal case of pentedrone and alpha-pyrrolidinovalerophenone poisoning. J Anal Toxicol 39:324–329PubMedGoogle Scholar
  143. Szmuszkovicz J, Von Voigtlander PF (1982) Benzeneacetamide amines: structurally novel non-m mu opioids. J Med Chem 25:1125–1126PubMedGoogle Scholar
  144. 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 54:1–13Google Scholar
  145. Takase I, Koizumi T, Fujimoto I, Yanai A, Fujimiya T (2016) An autopsy case of acetyl fentanyl intoxication caused by insufflation of “designer drugs”. Leg Med (Tokyo) 21:38–44Google Scholar
  146. Tarpgaard M, Maerkedahl R, Lauridsen KB (2015) Fatal intoxication with the new designer drug 25C-NBOMe. Ugeskr Laeger 177(35). pii: V09140523Google Scholar
  147. Thirakul P, L SH KLB, MP J (2017) Clinical presentation, autopsy results and toxicology findings in an acute N-ethylpentylone fatality. J Anal Toxicol 41:342–346PubMedGoogle Scholar
  148. Thompson I, Williams G, Caldwell B, Aldington S, Dickson S, Lucas N, McDowall J, Weatherall M, Robinson G, Beasley R (2010) Randomised double-blind, placebo-controlled trial of the effects of the “party pills” BZP/TFMPP alone and in combination with alcohol. J Psychopharmacol 24:1299–1308PubMedGoogle Scholar
  149. Thornton SL, Gerona RR, Tomaszewski CA (2012) Psychosis from a bath salt product containing flephedrone and MDPV with serum, urine, and product quantification. J Med Toxicol 8:310–313PubMedPubMedCentralGoogle Scholar
  150. Tiscione NB, Shanks KG (2016) Carfentanil identified in two driving under the influence of drugs cases. Toxtalk 40:14–17Google Scholar
  151. Torrance H, Cooper G (2010) The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland. Forensic Sci Int 202:e62–e63PubMedGoogle Scholar
  152. Trecki J, Gerona RR, Schwartz MD (2015) Synthetic cannabinoid-related illnesses and deaths. N Engl J Med 373:103–107PubMedGoogle Scholar
  153. UNODC (2017a) Global overview of drug demand and supply. World Drug Report 2017Google Scholar
  154. UNODC (2017b) Market analysis of synthetic drugs. World Drug Report 2017Google Scholar
  155. Usui K, Aramaki T, Hashiyada M, Hayashizaki Y, Funayama M (2014) Quantitative analysis of 3,4-dimethylmethcathinone in blood and urine by liquid chromatography-tandem mass spectrometry in a fatal case. Leg Med (Tokyo) 16:222–226Google Scholar
  156. Usui K, Fujita Y, Kamijo Y, Kokaji T, Funayama M (2017) Identification of 5-fluoro ADB in human whole blood in four death cases. J Anal Toxicol 42:e21–e25Google Scholar
  157. Vakkalanka JP, Charlton NP, Holstege CP (2017) Epidemiologic trends in loperamide abuse and misuse. Ann Emerg Med 69:73–78PubMedGoogle Scholar
  158. Wallach J, Kang H, Colestock T, Morris H, Bortolotto ZA, Collingridge GL, Lodge D, Halberstadt AL, Brandt SD, Adejare A (2016) Pharmacological investigations of the dissociative “Legal Highs” diphenidine, methoxphenidine and analogues. PLoS One 11:e0157021PubMedPubMedCentralGoogle Scholar
  159. Walterscheid JP, Phillips GT, Lopez AE, Gonsoulin ML, Chen HH, Sanchez LA (2014) Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. Am J Forensic Med Pathol 35:20–25PubMedGoogle Scholar
  160. Warrick BJ, Wilson J, Hedge M, Freeman S, Leonard K, Aaron C (2012) Lethal serotonin syndrome after methylone and butylone ingestion. J Med Toxicol 8:65–68PubMedGoogle Scholar
  161. Westin AA, Frost J, Brede WR, Gundersen POM, Einvik S, Aarset H, Slørdal L (2016) Sudden cardiac death following use of the synthetic cannabinoid MDMB-CHMICA. J Anal Toxicol 40:86–87PubMedGoogle Scholar
  162. Westphal F, Junge T, Rosner P, Sonnichsen F, Schuster F (2009) Mass and NMR spectroscopic characterization of 3,4-methylenedioxypyrovalerone: a designer drug with alpha-pyrrolidinophenone structure. Forensic Sci Int 190:1–8PubMedGoogle Scholar
  163. Vevelstad M, Oiestad EL, Middelkoop G, Hasvold I, Lilleng P, Delaveris GJ, Eggen T, Morland J, Arnestad M (2012) The PMMA epidemic in Norway: comparison of fatal and non-fatal intoxications. Forensic Sci Int 219:151–157PubMedGoogle Scholar
  164. White JM, Irvine RJ (1999) Mechanisms of fatal opioid overdose. Addiction 94:961–972PubMedGoogle Scholar
  165. Wiergowski M, Anand JS, Krzyzanowski M, Jankowski Z (2014) Acute methoxetamine and amphetamine poisoning with fatal outcome: a case report. Int J Occup Med Environ Health 27:683–690PubMedGoogle Scholar
  166. Wikstrom M, Thelander G, Dahlgren M, Kronstrand R (2013) An accidental fatal intoxication with methoxetamine. J Anal Toxicol 37:43–46PubMedGoogle Scholar
  167. Wikstrom M, Thelander G, Nystrom I, Kronstrand R (2010) Two fatal intoxications with the new designer drug methedrone (4-methoxymethcathinone). J Anal Toxicol 34:594–598PubMedGoogle Scholar
  168. Winklhofer S, Surer E, Ampanozi G, Ruder T, Stolzmann P, Elliott M, Oestreich A, Kraemer T, Thali M, Alkadhi H, Schweitzer W (2014) Post-mortem whole body computed tomography of opioid (heroin and methadone) fatalities: frequent findings and comparison to autopsy. Eur Radiol 24:1276–1282PubMedGoogle Scholar
  169. Winstock A, Mitcheson L, Ramsey J, Davies S, Puchnarewicz M, Marsden J (2011) Mephedrone: use, subjective effects and health risks. Addiction 106:1991–1996PubMedGoogle Scholar
  170. 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 6:327–330PubMedPubMedCentralGoogle Scholar
  171. Wood DM, Davies S, Puchnarewicz M, Johnston A, Dargan PI (2012) Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine. Eur J Clin Pharmacol 68:853–856PubMedGoogle Scholar
  172. Wood DM, Greene SL, Dargan PI (2011) Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone. Emerg Med J 28:280–282PubMedGoogle Scholar
  173. Wood DM, Greene SL, Dargan PI (2013) Emergency department presentations in determining the effectiveness of drug control in the United Kingdom: mephedrone (4-methylmethcathinone) control appears to be effective using this model. Emerg Med J 30:70–71PubMedGoogle Scholar
  174. Vorce SP, Knittel JL, Holler JM, Magluilo J Jr, Levine B, Berran P, Bosy TZ (2014) A fatality involving AH-7921. J Anal Toxicol 38:226–230PubMedGoogle Scholar
  175. Wright TH, Cline-Parhamovich K, Lajoie D, Parsons L, Dunn M, Ferslew KE (2013) Deaths involving methylenedioxypyrovalerone (MDPV) in upper East Tennessee. J Forensic Sci 58:1558–1562PubMedGoogle Scholar
  176. 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) 19:113–118Google Scholar
  177. Wyman JF, Lavins ES, Engelhart D, Armstrong EJ, Snell KD, Boggs PD, Taylor SM, Norris RN, Miller FP (2013) Postmortem tissue distribution of MDPV following lethal intoxication by “bath salts”. J Anal Toxicol 37:182–185PubMedGoogle Scholar
  178. Yeter O (2017) Identification of the synthetic cannabinoid 1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H-indazole-3-carboxamide (CUMYL-4CN-BINACA) in plant material and quantification in post-mortem blood samples. J Anal Toxicol 41:720–728PubMedGoogle Scholar
  179. Yonemitsu K, Sasao A, Mishima S, Ohtsu Y, Nishitani Y (2016) A fatal poisoning case by intravenous injection of “bath salts” containing acetyl fentanyl and 4-methoxy PV8. Forensic Sci Int 267:e6–e9PubMedGoogle Scholar
  180. Zaitsu K, Nakayama H, Yamanaka M, Hisatsune K, Taki K, Asano T, Kamata T, Katagai M, Hayashi Y, Kusano M, Tsuchihashi H, Ishii A (2015) High-resolution mass spectrometric determination of the synthetic cannabinoids MAM-2201, AM-2201, AM-2232, and their metabolites in postmortem plasma and urine by LC/Q-TOFMS. Int J Leg Med 129:1233–1245Google Scholar
  181. Zuba D, Sekula K, Buczek A (2013) 25C-NBOMe – new potent hallucinogenic substance identified on the drug market. Forensic Sci Int 227:7–14PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Robert Kronstrand
    • 1
    • 2
    Email author
  • Davide Guerrieri
    • 1
    • 2
  • Svante Vikingsson
    • 1
    • 2
  • Ariane Wohlfarth
    • 1
    • 2
  • Henrik Gréen
    • 1
    • 2
  1. 1.Department of Forensic Genetics and Forensic ToxicologyNational Board of Forensic MedicineLinköpingSweden
  2. 2.Division of Drug ResearchLinköping UniversityLinköpingSweden

Personalised recommendations