Forensic Toxicology

, Volume 34, Issue 2, pp 201–212 | Cite as

Old opioids, new concerns: the case of acetylfentanyl

  • Maria Katselou
  • Ioannis Papoutsis
  • Panagiota NikolaouEmail author
  • Chara Spiliopoulou
  • Sotiris Athanaselis
Review Article


Acetylfentanyl is a potent synthetic opioid analgesic that has been increasingly available in America, Europe, Japan, China, and Australia during the last years. It has no approved medical or veterinary use, but it is used illicitly around the world as a substitute of its controlled precursor, fentanyl, as well as of heroin or other related substances in opioid dependent individuals. It is available in retail or “head shops” or over the Internet by companies based mainly in China. Acetylfentanyl is available in the form of powder, tablets, and blotters, while liquid and injectable formulations have been also reported. Acetylfentanyl seizures have dramatically increased during the last 4 years, and its abuse has already caused a number of deaths in the United States, the United Kingdom, Sweden, and Japan, thus leading to its scheduling under the 1961 Single Convention on Narcotic Drugs in the United States, and some European Countries, China, and Japan since 2015. The aim of this review is to summarize the current knowledge about this drug concerning its chemistry, synthesis, prevalence, metabolism, pharmacology, and toxicology, as well as its legal status. Analytical methodologies developed for the determination of acetylfentanyl in biological specimens, as well as published or reported acetylfentanyl related cases, fatal or not, and self reports from drug users are presented.


Acetylfentanyl μ-Opioid receptor agonist Analytical methods Prevalence Legislation 


Compliance with ethical standards

Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Collier R (2013) Street versions of opioids more potent and dangerous. Can Med Assoc J 185:1027CrossRefGoogle Scholar
  2. 2.
    European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2015) European Drug Report. Trends and developments. Lisbon Portugal. Accessed 21 January 2016
  3. 3.
    Erowid (2015) Acetylfentanyl. acetylfentanyl.shtml. Accessed 9 January 2016
  4. 4.
    Stogner JM (2015) Predictions instead of panics: the framework and utility of systematic forecasting of novel psychoactive drug trends. Am J Drug Alcohol Abuse 41:519–526CrossRefPubMedGoogle Scholar
  5. 5.
    World Health Organization (WHO) (2015) Acetylfentanyl. Critical review report. Agenda item 5.2. Expert Committee on Drug Dependence 37th Meeting. Geneva 16–20 November 2015. Accessed 20 December 2015
  6. 6.
    World Health Organization (WHO) (2015) Expert peer review No. 1. Agenda item 5.2: acetylfentanyl. Expert Committee on Drug Dependence (ECDD) 37th Meeting Geneva, 16–20 November 2015. Accessed 20 December 2016
  7. 7.
    Banonimuss (2015) Acetyl-fentanyl/varying dosages-first time. Accessed 10 January 2016
  8. 8.
    Drugs-Forum (2015) Acetyl fentanyl or Butyr fentanyl? Accessed 10 January 2016
  9. 9.
    U.S. Department of Justice, Drug Enforcement Administration (DEA) Office of Diversion Control Drug & Chemical Evaluation Section (2015) Acetyl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide). Drug Enforcement Administration OoDC, Drug & Chemical Evaluation Section, ArlingtonGoogle Scholar
  10. 10.
    Garg A, Solas DW, Takahashi LH, Cassella JV (2010) Forced degradation of fentanyl: identification and analysis of impurities and degradants. J Pharm Biomed Anal 53:352–354CrossRefGoogle Scholar
  11. 11.
    Soine WH (1986) Clandestine drug synthesis. Med Res Rev 6: 41–74. Accessed 9 January 2016
  12. 12.
    Wikipedia (2015) Acetylfentanyl. Accessed 10 November 2015
  13. 13.
  14. 14.
    Drug Enforcement Administration (DEA) (2013) Acetyl Fentanyl. Latest Revision: 12/16/2013. Accessed 9 November 2015Google Scholar
  15. 15.
    Brine GA, Boldt KG, Huang PT, Sawyer DK, Carroll FI (1989) Carbon-13 nuclear magnetic resonance spectra of fentanyl analogs. Heterocycl Chem 26:677–686CrossRefGoogle Scholar
  16. 16.
    Ohta H, Suzuki S, Ogasawara K (1999) Studies on fentanyl and related compounds IV. Chromatographic and spectrometric discrimination of fentanyl and its derivatives. J Anal Toxicol 23:280–285CrossRefPubMedGoogle Scholar
  17. 17.
    Valdez CA, Leif RN, Mayer BP (2014) An efficient, optimized synthesis of fentanyl and related analogs. PLoS ONE 9:e108250CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Janssen PAJ (1964) N-(1-aralkyl-4piperidyl)alkanoic acid anilides. N. V. Research Laboratorium, Dr. C. Janssen. FRM 2430Google Scholar
  19. 19.
    European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2015) Fentanyl drug Profile. Accessed 10 January 2016
  20. 20.
    Expert Committee on Drug Dependence (ECDD) (2015) Report on WHO questionnaire for review of psychoactive substances for the 37th ECDD: evaluation of acetylfentanyl. Agenda item 5.2 acetylfentanyl. 37th ECDD Meeting, 2015. Accessed 20 December 2015
  21. 21.
    Drug Enforcement Administration (DEA) Department of Justice (2015) Schedules of controlled substances: temporary placement of acetyl fentanyl into Schedule I. Fed Regist 80:42381–42385Google Scholar
  22. 22.
    Stogner JM (2014) The potential threat of acetyl fentanyl: legal issues, contaminated heroin, and acetyl fentanyl “disguised” as other opioids. Ann Emerg Med 64:637–639CrossRefPubMedGoogle Scholar
  23. 23.
    Jorge R (2015) Deaths in Europe associated with acetylfenyanyl. EU Early Warning System Alert, EMCDDA. Accessed 10 November 2015
  24. 24.
    Evans-Brown M (2015) Subject: 2 deaths associated with acetyl fentanyl in the United Kingdom. EU Early Warning System Alert, EMCDDA, LisbonGoogle Scholar
  25. 25.
    Melent’ev AB, Kataev SS, Dvorshaya ON (2015) Identification and analytical properties of acetyl fentanyl metabolites. J Anal Chem 70:240–248CrossRefGoogle Scholar
  26. 26.
    Erowid (2015) Tested the waters a lot: an experience with acetylfentanyl & various (ID 106907). Accessed 9 January 2016
  27. 27.
    Erowid (2015) 100% pain relief: an experience with acetylfentanyl (ID 102018). Accessed 9 January 2016
  28. 28.
    Erowid (2015) First time out: an experience with acetylfentanyl (ID 106838). Accessed 9 January 2016
  29. 29.
    Erowid (2015) I realized I was becoming addicted: an experience with acetylfentanyl (ID 107307). Accessed 9 January 2016
  30. 30.
    Patton AL, Seely KA, Pulla S, Rusch NJ, Moran CL, Fantegrossi WE, Knight LD, Marraffa JM, Kennedy PD, James LP, Endres GW, Moran JH (2014) Quantitative measurement of acetyl fentanyl and acetyl norfentafyl in human urine by LC–MS/MS. Anal Chem 86:1760–1766CrossRefPubMedGoogle Scholar
  31. 31.
    World Health Organization (WHO) (2015) Expert peer review No. 2. Agenda item 5.2: acetylfentanyl. Expert Committee on Drug Dependence (ECDD) 37th Meeting Geneva, 16–20 November 2015. Accessed 20 December 2016
  32. 32.
    Higashikawa Y, Suzuki S (2008) Studies on 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (fentanyl) and its related compounds. VI. Structure-analgesic activity relationship for fentanyl, methyl-substituted fentanyls and other analogues. Forensic Toxicol 26:1–5CrossRefGoogle Scholar
  33. 33.
    Aceto M, Bowman E, Harris L, May E (1988) Dependence studies of new compounds in the rhesus monkey, rat, and mouse. NIDA Res Monogr 81:485–542PubMedGoogle Scholar
  34. 34.
    Centers for Disease and Control and Prevention (CDC) Health Advisory (2013) Emergency preparedness and response. Recommendations for laboratory testing for acetyl fentanyl and patient evaluation and treatment for overdose with synthetic opioid. Accessed 8 January 2016
  35. 35.
    Drug Policy Alliance (2015) Opioid overdose: addressing the growing problem of preventable deaths. Accessed 10 January 2016
  36. 36.
    Wermeling DP (2015) Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access. Ther Adv Drug Saf 6:20–31CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Schumann H, Erickson T, Thompson TM, Zautcke JL, Denton JS (2008) Fentanyl epidemic in Chicago, Illinois and surrounding Cook County. Clin Toxicol 46:501–506CrossRefGoogle Scholar
  38. 38.
    Walley AY, Xuan Z, Hackmann HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A (2013) Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. Brit Med J 346:f174CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    News C (2015) Extremely potent painkiller hits Montreal black market: Desmehtyl fentanyl is 40 times more potent than heroin. Accessed 10 January 2016
  40. 40.
    Europol (2013) Reporting form on new psychoactive drug. Acetyl fentanyl. Germany. 18.09.2013. HagueGoogle Scholar
  41. 41.
    European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2015) European Database on New Drugs (EDND) AcetylfentanylGoogle Scholar
  42. 42.
    Europol (2014) Reporting form on new psychoactive drug. Acetyl fentanyl. Finland. 11.12.2014. HagueGoogle Scholar
  43. 43.
    Europol (2015) Reporting form on new psychoactive drug. Acetyl fentanyl. France. 17.03.2015. HagueGoogle Scholar
  44. 44.
    Europol (2015) Reporting form on new psychoactive drug. Acetyl fentanyl. Sweden. 02.05.2015. HagueGoogle Scholar
  45. 45.
    Europol (2015) Reporting form on new psychoactive drug. Acetyl fentanyl. United Kingdom. 07.05.2015. HagueGoogle Scholar
  46. 46.
    Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl)benzofural (2-EAPB), eight synthetic cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281CrossRefGoogle Scholar
  47. 47.
    Knowles G (2015) Opiate disguised as Pez lollies. The West Australian. Accessed 10 January 2016
  48. 48.
    Sparvell R (2015) Lolly warning: ‘Pez’-like drugs seized by WA organized crime detectives. WA Today. Accessed 10 January 2016
  49. 49.
    Department of Health and Human Services (DHHS) (2014) DHHS issues health advisory for deadly new synthetic drug, Acetyl fentanyl detected in specimens associated with three N.C. deaths this year. Accessed 10 November 2015
  50. 50.
    Ogilvie L, Stanley C, Lewis L, Boyd M, Lozier M (2013) Acetyl fentanyl overdose fatalities—Rhode Island, March–May 2013. MMWR 62:703–704Google Scholar
  51. 51.
    Lozier MJ, Boyd M, Stanley C, Ogilvie C, King E, Martin C, Lewis L (2015) Acetyl fentanyl, a novel fentanyl analog, cause 14 overdose deaths in Rhode Island, March-May 2013. J Med Toxicol 11:208–217CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Isenschmid D, Kacinko S, Logan B (2014) Case findings in 18 acetylfentanyl related deaths. World Forensic Festival, IAFS, Seoul, KoreaGoogle Scholar
  53. 53.
    Cunningham AM, Bailey KM, Newsome-Sparks CL, Gebhardt MA, Clay DJ, Venuti SA, Haikal NA, Kraner JC (2015) Fatal intoxication with acetyl fentanyl. J Forensic Sci. doi: 10.1111/1556-4029.12953 Google Scholar
  54. 54.
    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 257:435–441CrossRefPubMedGoogle Scholar
  55. 55.
    Zhang X, Jufer Phipps R, Levine BS, Aronica P, Locke J, Brassell MA, Warren WS, Ripple MG, Fowler DR (2015) Postmortem distribution of acetyl fentanyl. 67th Annual Meeting of AAFS, Orlando, Florida, 2015Google Scholar
  56. 56.
    McIntyre IM, Trochta A, Gary RD, Malamatos M, Lucas JR (2015) An acute acetyl fentanyl fatality: a case report with post mortem concentrations. J Anal Toxicol 39:490–494CrossRefPubMedGoogle Scholar
  57. 57.
    Dewey P (2015) Cardiff man died after taking legal designer drug ‘five times stronger than heroin’. Wales. Accessed 10 November 2015
  58. 58.
    Hisatsune K, Zaitsu K, Yamanaka M, Nakajima J, Moriyasu T, Ishiba A, Hida M, Tsuchihashi H, Ishii A (2015) Determination of newly encountered designer drugs α-PHP and acetylfentanyl in an acute intoxication case by LC/Q–TOF MS. 53rd TIAFT Meeting, Firenze 2015Google Scholar
  59. 59.
    Wang B-T, Colby JM, Wu AHB, Lynch KL (2014) Cross-reactivity of acetyl fentanyl and risperidone with a fentanyl immunoassay. J Anal Toxicol 38:672–675CrossRefPubMedGoogle Scholar
  60. 60.
    Ruangyuttikarn W, Law MY, Rollins DE, Moody DE (1990) Detection of fentanyl and its analogues by enzyme-linked immunosorbent assay. J Anal Toxicol 14:160–164CrossRefPubMedGoogle Scholar
  61. 61.
    Centers for Disease and Control and Prevention (2013) Recommendations for laboratory testing for acetyl fentanyl and patient evaluation and treatment for overdose with synthetic opioid. Centers for Disease and Control and Prevention, Atlanta, pp 1–3Google Scholar
  62. 62.
    Commission on Narcotic Drugs (2015) Implementation of the international drug control treaties: changes in the scope of control of substances. Extract from the Report of the 37th Expert Committee on Drug Dependence Substance recommended to be scheduled in Schedule I and Schedule IV of the Single Convention on Narcotic Drugs (1961), as amended by the 1972 Protocol: acetylfentanyl. Vienna, 9–11 December 2015Google Scholar
  63. 63.
    International Narcotics Control Board (2014) Yellow List. List of narcotic drugs under international control. Annex to Forms A, B and C, 53rd edn., December 2014. Single Convention on Narcotic Drugs, Vienna, 1961. Protocol of 25 March 1972 amending the Single Convention on Narcotic Drugs, 1961Google Scholar

Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2016

Authors and Affiliations

  • Maria Katselou
    • 1
  • Ioannis Papoutsis
    • 1
  • Panagiota Nikolaou
    • 1
    Email author
  • Chara Spiliopoulou
    • 1
  • Sotiris Athanaselis
    • 1
  1. 1.Department of Forensic Medicine and Toxicology, Faculty of MedicineNational and Kapodistrian University of AthensAthensGreece

Personalised recommendations