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 Table of Contents  
BRIEF COMMUNICATION
Year : 2016  |  Volume : 2  |  Issue : 2  |  Page : 111-114

Resurgence of Fentanyl as a Drug of Abuse


Department of Public Services, Oakland County Medical Examiners' Office, Oakland County, Pontiac, Michigan 48341, USA

Date of Web Publication16-Jun-2016

Correspondence Address:
Ljubisa Jovan Dragovic
Oakland County Medical Examiner's Office, Oakland County, 1200 N. Telegraph #28 East, Pontiac, Michigan 4834
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-5014.184195

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  Abstract 


Fentanyl, a powerful opioid analgesic introduced over 50 years ago, has a major role in modern anesthesia and chronic pain relief but has also gained a major role in illicit use. After a spike in fentanyl abuse between 2005 and 2007, fentanyl deaths decreased until 2010, with the introduction of “abuse-deterrent” OxyContin. Our data indicate a recent rise in fentanyl-related deaths beginning in 2013, which follows national trends. With the re-emergence of the synthetic narcotic analgesic of high potency as a popular drug of abuse and the alarmingly increasing mortality associated with its abuse, there are profound implications for public health, health care providers, law enforcement, and the society in general.

Keywords: Abuse, fentanyl, OxyContin, synthetic opioids


How to cite this article:
Tamburro LP, Al-Hadidi JH, Dragovic LJ. Resurgence of Fentanyl as a Drug of Abuse. J Forensic Sci Med 2016;2:111-4

How to cite this URL:
Tamburro LP, Al-Hadidi JH, Dragovic LJ. Resurgence of Fentanyl as a Drug of Abuse. J Forensic Sci Med [serial online] 2016 [cited 2018 Dec 17];2:111-4. Available from: http://www.jfsmonline.com/text.asp?2016/2/2/111/184195




  Introduction Top


Opioid analgesics include many compounds with vast application of everyday treatment of pain; however, deaths resulting from the abuse of opioids, both prescription and illicit, reached all-time high in the past 2 years. There had been an almost 3 times increase in the rate of heroin abuse deaths in the United States between 2010 and 2014, and the rate of oxycodone and hydrocodone abuse-related deaths doubled in 2014, compared to the year before.

Toxicology analyses of deaths in both of these groups revealed that illicitly-made fentanyl had been an emerging critical factor in the deadly mix.

Fentanyl early years

Fentanyl, a potent lipid-soluble opioid analgesic about 50–100 times more potent than morphine and 30–50 times more powerful than heroin,[1] was first synthesized in Belgium in December 1960.[2] After a push by Dr. Paul Janssen, of Janssen Pharmaceutica, to get fentanyl exposed to anesthesiologists in the United States, fentanyl was first used in anesthesia in 1968 due to its high potency and rapid onset (2–3 min).[2],[3] The success of high-dose fentanyl/oxygen anesthesia led to the creation of a fentanyl skin patch called Duragesic, which was approved by the Food and Drug Administration (FDA) in 1990 and introduced by Janssen in 1991.[2] Abuse of fentanyl initially appeared in the mid-1970s and has increased in recent years.[4]

Illicit fentanyl

In 2005, illicitly manufactured nonpharmaceutical fentanyl (NPF) began production in a clandestine laboratory in Toluca, Mexico, for distribution in the United States and other countries.[5] This led to over 1000 deaths being attributed to NPF across the United States, particularly in major urban areas such as Chicago, Detroit, and Philadelphia.[6] Drug Enforcement Administration (DEA) traced the fentanyl back to a single laboratory in Mexico in early 2007.[5] Once the laboratory was shut down, the fentanyl supply and related deaths ended. To prevent re-emergence of the fentanyl, on April 23, 2007, DEA began regulating access to N-phenethyl-4-piperidone (NPP), a necessary component in the production of fentanyl.[6] This control on NPP also led to the continuing decline in fentanyl-related deaths.

New OxyContin formula

Fentanyl-related deaths would begin to rise as a consequence of FDAs approval of a new formulation of OxyContin, whose active ingredient is oxycodone. This new formulation was designed to discourage misuse and abuse of the medication in April 2010, and was released for use in August 2010.[7] A survey funded by the Denver Health and Hospital Authority and published in the New England Journal of Medicine showed that the introduction of the abuse-deterrent formulation of OxyContin led to a decrease in the selection of OxyContin as a primary drug of abuse.[8] Twenty-one months after the release of the abuse-deterrent formulation, respondents reported a decrease in the use of OxyContin as the primary drug of abuse from 35.6% to 12.8%.[8] However, for other opioids, including fentanyl, respondents indicated a rise in selection from 20.1% to 32.3%.[8] Of the 2566 respondents, 66% indicated a switch to another opioid.[8] In a phone or online interview, most respondents admitted to simply changing their preferred drug of choice from OxyContin to other analgesics such as heroin, fentanyl, hydrocodone, or other opioids because it is much easier to use as well as cost-effective.[8] It is important to note that most drug abusers did not cease their drug use, but instead shifted their drug of choice.[8]

Resurgence of fentanyl

After the rise in the use of other opioids following the release of the new formula of OxyContin, fentanyl has increasingly been seen laced in heroin and being abused on its own.[4] Between 2013 and 2014, DEA has seen a significant resurgence in fentanyl-related seizures.[1] According to the National Forensic Laboratory Information System, state and local laboratories saw a 3.5-fold increase in fentanyl seizures from 942 fentanyl submissions in 2013 to 3344 in 2014.[1] These seizures have been determined to have originated from Mexican drug trafficking organizations.[1] Another effect of the new formula of OxyContin is the rise in availability of counterfeit oxycodone pills that contain fentanyl in parts of Canada and more recently in Tennessee. According to Health Canada's Drug Analysis Service, in 2014, 89% of all seized counterfeit oxycodone tablets contained fentanyl as the active ingredient.[9] On May 14, 2015, these counterfeit pills reached the Unites States when several 30 mg pills were seized in Tennessee by the Tennessee Bureau of Investigation.[10] Given the presence of fentanyl in these counterfeit pills, individuals who believe they are using oxycodone are at greater risk of an accidental overdose.


  Methods Top


Postmortem data were obtained from the OCME electronic database for all deaths involving fentanyl between the years 2010 and 2015. In this database manner of death can be listed as natural, accident, suicide, homicide, undeterminable, or private. Excluding private cases, which cannot disclose information on the cause of death, all manners of death except undeterminable are in concurrence with causes of death other than drug abuse. When the manner of death is undeterminable, the cause of death is most often drug abuse, except in some cases of infant death; however, these infants did not show positive screens for fentanyl, so these cases do not impact the study. Therefore, this distinction between manners of death could be used to separate cases of prescribed fentanyl from fentanyl abuse and overdose. In addition, other drugs and drug classes that were concurrently detected with the fentanyl were broken into the following groups; tetrahydrocannabinol (THC), benzodiazepines, cocaine, heroin, and other opiates. Different specimen types in each autopsy case include: Heart blood, femoral blood, urine, vitreous humor, and other tissues and fluids and were confirmed by gas chromatography/mass spectrometry (GC/MS) by National Medical Services Laboratories. Due to lack of testing for the Schedule I street drug acetyl fentanyl before 2015, no attempt was made to discriminate between the presence of any one specific analog of the Schedule II fentanyl. In addition, even though other fentanyl analogs such as carfentanil or sufentanil were screened for, the Neogen Corporation's Fentanyl ELISA test kit used to screen for fentanyl and its metabolites and analogs have high specificity for fentanyl, p-fluorofentanyl, and thienylfentanyl over the other analogs, which have a percent cross-reactivity lower than 50. This means these other compounds are less likely to be detected, and thus, it is not cost-effective to discriminate between them.


  Results Top


In 2010, the toxicologists at Oakland County Medical Examiner's Office tested specimens from 958 cases. Thirty-eight (4.0%) of these cases were positive for fentanyl. In 8 (21.1%) of the cases positive for fentanyl, the cause of death was determined to be drug abuse. In 2011, specimens were tested from 1029 cases. Twenty-eight (2.7%) of these cases were positive for fentanyl. In 6 (21.4%) of the cases positive for fentanyl, the cause of death was determined to be drug abuse. In 2012, specimens were tested from 1082 cases. Thirty (2.8%) of these cases were positive for fentanyl. In 14 (46.7%) of the cases positive for fentanyl, the cause of death was determined to be drug abuse. In 2013, specimens were tested from 1014 cases. Forty-two (4.1%) of these cases were positive for fentanyl. In 17 (40.5%) of the cases positive for fentanyl, the cause of death was determined to be drug abuse. In 2014, specimens were tested from 1037 cases. Seventy-eight (7.5%) of these cases were positive for fentanyl. In 48 (61.5%) of the cases positive for fentanyl, the cause of death was determined to be drug abuse. In 2015, specimens were tested from 616 cases up until August 04, 2015. Sixty-eight (11.0%) of these cases were positive for fentanyl. In 42 (61.8%) of the cases positive for fentanyl, the cause of death was determined to be drug abuse. Concurrence of the other drugs and other drug classes in the fentanyl cases followed a similar pattern with opiates>benzodiazepines>THC>cocaine>heroin. Discrepancies in this pattern were seen in 2011 as well as 2013 where cocaine and heroin were both found in the same number of cases and in 2012, where cocaine was present in more cases than THC [Figure 1] and [Table 1].
Figure 1: (a) Trend in fentanyl-related deaths in comparison with number determined to be of indeterminable manner with cause of death being drug abuse; (b) Percentage of total fentanyl cases where cause of death was drug abuse

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Table 1: Co-administered substances identified in fatalities associated with indeterminate (licit or illicit) fentanyl use

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  Conclusion Top


In our 6-year retrospective study, 54 of 280 total fentanyl cases were found where fentanyl was the sole drug present. A high prevalence of concurrent use of other opioids and benzodiazepines was also seen. In accordance with current national trends, the percentage of cases of fentanyl determined to be drug abuse cases has increased significantly from 21.1% in 2010 to 61.5% in 2014, a 3-fold increase. It is clear that this trend is not only continuing but also increasing. In 2015, the Oakland County Medical Examiner's Office has seen 64 total fentanyl cases with 60.9% determined to be drug abuse cases in just over 6 months. Consequently, care needs to be taken to ensure proper screening in toxicology by including fentanyl in routine testing. We recommend using an ELISA test to screen specimens from suspected overdose deaths and if positive for fentanyl have laboratories conduct confirmatory quantitative testing by GC/MS. Although not commonly used by toxicologists due to its high costs, according to Zeng et al., liquid chromatography/MS (LC/MS) is becoming increasingly employed to achieve accurate results more quickly.[11] If no fentanyl is detected by GC/MS or LC/MS, then fentanyl analogs should be suspected, and subsequent ELISA testing should be considered.

In addition, with this dangerous rise in fentanyl abuse cases, safety for the law enforcement that could come into contact with fentanyl is paramount. As fentanyl can be absorbed through the skin or accidentally inhaled as an airborne powder, there is concern about law enforcement coming in contact with fentanyl on the streets during the course of enforcement such as a buy-walk, or buy-bust operation.[1] To increase the safety of law enforcement, we recommend law enforcement carry a high dosage of naloxone with them, due to the high potency of fentanyl, in case of accidental exposure to fentanyl intoxication.

Furthermore, the brief overview of these detrimental trends clearly indicates that any long-term, organized societal effort to effectively curb the dangerous situation should refocus on the attempts to minimize or eliminate the demand for the substances of abuse.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
U.S. Drug Enforcement Administration. DEA Issues Nationwide Alert on Fentanyl as Threat to Health and Public Safety. DEA Headquarters News, 2015. Available from: http://www.dea.gov/divisions/hq/2015/hq031815.shtml. [Last accessed on 2015 Aug 11].  Back to cited text no. 1
    
2.
Stanley TH. The fentanyl story. J Pain 2014;15:1215-26.  Back to cited text no. 2
    
3.
Thompson JG, Baker AM, Bracey AH, Seningen J, Kloss JS, Strobl AQ, et al. Fentanyl concentrations in 23 postmortem cases from the Hennepin County Medical Examiner's Office. J Forensic Sci 2007;52:978-81.  Back to cited text no. 3
    
4.
Jumbelic MI. Deaths with transdermal fentanyl patches. Am J Forensic Med Pathol 2010;31:18-21.  Back to cited text no. 4
    
5.
Denton JS, Donoghue ER, McReynolds J, Kalelkar MB. An epidemic of illicit fentanyl deaths in Cook County, Illinois: September 2005 through April 2007. J Forensic Sci 2008;53:452-4.  Back to cited text no. 5
    
6.
Centers for Disease Control and Prevention (CDC). Non-pharmaceutical fentanyl-related deaths – Multiple states, April 2005-March 2007. MMWR Morb Mortal Wkly Rep 2008;57:793-6.  Back to cited text no. 6
[PUBMED]    
7.
U.S Food and Drug Administration. FDA Approves New Formulation for Oxy Contin. FDA: Press Announcements,2010. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm207480.htm. [Last accessed on 2015 Aug 11].  Back to cited text no. 7
    
8.
Cicero TJ, Ellis MS, Surratt HL. Effect of abuse-deterrent formulation of OxyContin. N Engl J Med 2012;367:187-9.  Back to cited text no. 8
[PUBMED]    
9.
Canadian Centre on Substance Abuse (CCSA). CCENDU Drug Alert: Increasing Availability of Counterfeit Oxycodone Tablets Containing Fentanyl. CCSA,2014. Available from: http://www.ccsa.ca/Resource%20Library/CCSA-CCENDU-Oxycontin-Fentanyl-Alert-2014-en.pdf. [Last accessed on 2015 Aug 11].  Back to cited text no. 9
    
10.
De Vine J. TBI Issues Public Safety Alert for Potentially Deadly Pills. TBI: Newsroom,2015. Available from: http://www.tbinews.wordpress.com/2015/05/14/tbi-issues-public-safety-alert-for- potentially-deadly-pills/. [Last accessed on 2015 Aug 11].  Back to cited text no. 10
    
11.
Zeng L, Liu Z, Han X, Hao H. Advances in toxins and narcotics determination techniques in China during 2013. J Forensic Sci Med 2015;1:54-60.  Back to cited text no. 11
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    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]


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