Growing international evidence, obtained in recent years, documents increasing numbers of serious adverse events and deaths associated with several emerging synthetic opioids. Cases confirmed by toxicological analysis include deaths caused by: acetylfentanyl* - 21 cases in the USA [1][2][3][4] and 1 case in Japan [5], butyrylfentanyl - 3 cases in the USA [6][7] and 1 case in Switzerland [8], furanylfentanyl - 3 cases in the USA [9], ocfentanil - 1 case in Belgium [10] and 1 case in Switzerland [11], 4-fluorobutyrfentanyl – 2 cases in Poland [12], AH-7921* - 1 case in Sweden [13] and 1 case in the USA [14], MT-45* – 1 case in the USA [15], U-47700 - 58 cases in the USA [9][16][17] and 1 case in the United Kingdom [18].

In addition, cases reported to the EMCDDA in recent years include: 8 acute intoxications and 32 deaths associated with acetylfentanyl in Germany, Poland, Sweden, and the United Kingdom [19], 15 deaths associated with AH-7921 in Norway, Sweden and the United Kingdom[20], and 28 deaths associated with MT-45 in Sweden [21]. Of late, 23 deaths associated with acrylfentanyl were reported in Sweden in 2016 [22].

* acetylfentanyl, AH-7921 and MT-45 are under international control.

References

[1] Fort C, Curtis B, Nichols C, Niblo C. Acetyl Fentanyl Toxicity: Two Case Reports. Journal of Analytical Toxicology. 2016 Jul 13.

[2] Lozier MJ, Boyd M, Stanley C, Ogilvie L, King E, Martin C, Lewis L. Acetyl Fentanyl, a Novel Fentanyl Analog, Causes 14 Overdose Deaths in Rhode Island, March-May 2013. Journal of medical toxicology: official journal of the American College of Medical Toxicology. 2015 Jun;11(2):208-17.

[3] McIntyre IM, Trochta A, Gary RD, Wright J, Mena O. An acute butyr-fentanyl fatality: a case report with postmortem concentrations. Journal of analytical toxicology. 2016 Mar 1;40(2):162-6.

[4] Poklis J, Poklis A, Wolf C, Mainland M, Hair L, Devers K, Chrostowski L, Arbefeville E, Merves M, Pearson J. Postmortem tissue distribution of acetyl fentanyl, fentanyl and their respective nor-metabolites analyzed by ultrahigh performance liquid chromatography with tandem mass spectrometry. Forensic Science International. 2015 Dec 31;257:435-41.

[5] Takase I, Koizumi T, Fujimoto I, Yanai A, Fujimiya T. An autopsy case of acetyl fentanyl intoxication caused by insufflation of ‘designer drugs’. Legal Medicine. 2016 Jul 31;21:38-44.

[6] McIntyre IM, Trochta A, Gary RD, Wright J, Mena O. An acute butyr-fentanyl fatality: a case report with postmortem concentrations. Journal of analytical toxicology. 2016 Mar 1;40(2):162-6.

[7] Poklis J, Poklis A, Wolf C, Hathaway C, Arbefeville E, Chrostowski L, Devers K, Hair L, Mainland M, Merves M, Pearson J. Two fatal intoxications involving butyryl fentanyl. Journal of analytical toxicology. 2016 Jun 23.

[8] Staeheli SN, Baumgartner MR, Gauthier S, Gascho D, Jarmer J, Kraemer T, Steuer AE. Time-dependent postmortem redistribution of butyrfentanyl and its metabolites in blood and alternative matrices in a case of butyrfentanyl intoxication. Forensic Science International. 2016 Sep 30;266:170-7.

[9] Mohr AL, Friscia M, Papsun D, Kacinko SL, Buzby D, Logan BK. Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC–MS/MS in Postmortem Casework. Journal of Analytical Toxicology. 2016 Sep 1.

[10] Coopman V, Cordonnier J, De Leeuw M, Cirimele V. Ocfentanil overdose fatality in the recreational drug scene. Forensic Science International. 2016 Sep 30;266:469-73.

[11] Dussy FE, Hangartner S, Hamberg C, Berchtold C, Scherer U, Schlotterbeck G, Wyler D, Briellmann TA. An Acute Ocfentanil Fatality: A Case Report with Postmortem Concentrations. Journal of Analytical Toxicology. 2016 Sep 20.

[12] Rojkiewicz M, Majchrzak M, Celiński R, Kuś P, Sajewicz M. Identification and physicochemical characterization of 4‐fluorobutyrfentanyl (1‐((4‐fluorophenyl)(1‐phenethylpiperidin‐4‐yl) amino) butan‐1‐one, 4‐FBF) in seized materials and the postmortem biological samples. Drug Testing and Analysis. 2016 Jan 1.

[13] Kronstrand R, Thelander G, Lindstedt D, Roman M, Kugelberg FC. Fatal intoxications associated with the designer opioid AH-7921. Journal of analytical toxicology. 2014 Oct 1;38(8):599-604.

[14] Vorce SP, Knittel JL, Holler JM, Magluilo J, Levine B, Berran P, Bosy TZ. A fatality involving AH-7921. Journal of analytical toxicology. 2014 May 1;38(4):226-30.

[15] Papsun D, Krywanczyk A, Vose JC, Bundock EA, Logan BK. Analysis of MT-45, a Novel Synthetic Opioid, in Human Whole Blood by LC–MS-MS and Its Identification in a Drug-Related Death. Journal of analytical toxicology. 2016 May 1;40(4):313-7.

[16] McIntyre IM, Gary RD, Joseph S, Stabley R. A Fatality Related to the Synthetic Opioid U-47700: Postmortem Concentration Distribution. Journal of Analytical Toxicology. 2016 Oct 26.

[17] Drug Enforcement Administration, Department of Justice. Schedules of controlled substances: temporary placement of Temporary Placement of U-47700 into Schedule I. Final Order. Federal register. 2016 Sep 7;81(173): 61636.

[18] Elliott SP, Brandt SD, Smith C. 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 testing and analysis. 2016 May 27.

[19] EMCDDA–Europol Joint Report on acetylfentanyl, 2016

[20] EMCDDA Report on the risk assessment of AH-7921, 2014

[21] EMCDDA Report on the risk assessment of MT-45, 2015

[22] Rättsmedicinalverket. Akrylfentanyl narkotikaklassas. 2016. (Swedish). Retrieved from http://www.rmv.se/?id=433 on the 25 August 2016.