1. What is Fentanyl?

"Fentanyl is a synthetic opioid analgesic acting predominately at the μ-opiate receptor. It has historically been used as a pain reliever and an anaesthetic in both human and veterinary medicine and in terms of analgesic activity it is at least 80 times more potent than morphine. Fentanyl was first synthesized by Paul Janssen in 1960 and marketed as a medicinal product for treating pain. Subsequently, many fentanyl analogues were developed including sufentanil, alfentanil, remifentanil, and carfentanil. Fentanyl was first introduced for widespread palliative use in the mid-1990s in the form of transdermal patches, and to this day, it continues to be an important and much prescribed pain management medication in many countries. Concern surrounding the fentanyls is linked to their potential for dependence and misuse, their high potency and associated risk of fatal overdose."

Jane Mounteney, Isabelle Giraudon, Gleb Denissov, and Paul Griffiths, "Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe," International Journal of Drug Policy, Volume 26, Issue 7, 626 - 631. doi: 10.1016/j.drugpo.2015.04.003. Epub 2015 Apr 17.

2. Opioid Involvement in Deaths in the US Attributed to Drug Overdose, 2016

According to the Centers for Disease Control, in 2016, there were 63,632 drug overdose deaths in the United States. The CDC further estimates that of those, 42,249 deaths involved any opioid. The CDC further reports that in 2016, 15,469 deaths involved heroin; 14,487 deaths involved natural and semi-synthetic opioids; 3,373 deaths involved methadone; and 19,413 deaths involved synthetic opioids other than methadone, a category which includes fentanyl. The sum of those numbers is greater than the total opioid involved deaths because, as noted by the CDC, "Deaths involving more than one opioid category (e.g., a death involving both methadone and a natural or semisynthetic opioid such as oxycodone) are counted in both categories."

Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017.

3. Deaths from Drug Overdose in the United States

"During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states."

Rudd RA, Seth P, David F, Scholl L. Increases in Drug and Opioid-Involved Overdose Deaths — United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016;65:1445–1452. DOI: http://dx.doi.org/10.15585/mmw...

4. Growth of Fentanyl Related Deaths in the US

"Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50–100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans."

Julie K. O’Donnell, PhD; John Halpin, MD; Christine L. Mattson, PhD; Bruce A. Goldberger, PhD; R. Matthew Gladden, PhD. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016. Morbidity and Mortality Weekly Report. Vol. 66. Centers for Disease Control. October 27, 2017.

5. Involvement of Fentanyl in Overdose Deaths in the US

"Fentanyl was detected in 56.3% of 5,152 opioid overdose deaths in the 10 states during July–December 2016 (Figure). Among these 2,903 fentanyl-positive deaths, fentanyl was determined to be a cause of death by the medical examiner or coroner in nearly all (97.1%) of the deaths. Northeastern states (Maine, Massachusetts, New Hampshire, and Rhode Island) and Missouri** reported the highest percentages of opioid overdose deaths involving fentanyl (approximately 60%–90%), followed by Midwestern and Southern states (Ohio, West Virginia, and Wisconsin), where approximately 30%–55% of decedents tested positive for fentanyl. New Mexico and Oklahoma reported the lowest percentage of fentanyl-involved deaths (approximately 15%–25%). In contrast, states detecting any fentanyl analogs in >10% of opioid overdose deaths were spread across the Northeast (Maine, 28.6%, New Hampshire, 12.2%), Midwest (Ohio, 26.0%), and South (West Virginia, 20.1%) (Figure) (Table 1).
"Fentanyl analogs were present in 720 (14.0%) opioid overdose deaths, with the most common being carfentanil (389 deaths, 7.6%), furanylfentanyl (182, 3.5%), and acetylfentanyl (147, 2.9%) (Table 1). Fentanyl analogs contributed to death in 535 of the 573 (93.4%) decedents. Cause of death was not available for fentanyl analogs in 147 deaths.†† Five or more deaths involving carfentanil occurred in two states (Ohio and West Virginia), furanylfentanyl in five states (Maine, Massachusetts, Ohio, West Virginia, and Wisconsin), and acetylfentanyl in seven states (Maine, Massachusetts, New Hampshire, New Mexico, Ohio, West Virginia, and Wisconsin). U-47700 was present in 0.8% of deaths and found in five or more deaths only in Ohio, West Virginia, and Wisconsin (Table 1). Demographic characteristics of decedents were similar among overdose deaths involving fentanyl analogs and fentanyl (Table 2). Most were male (71.7% fentanyl and 72.2% fentanyl analogs), non-Hispanic white (81.3% fentanyl and 83.6% fentanyl analogs), and aged 25–44 years (58.4% fentanyl and 60.0% fentanyl analogs) (Table 2).
"Other illicit drugs co-occurred in 57.0% and 51.3% of deaths involving fentanyl and fentanyl analogs, respectively, with cocaine and confirmed or suspected heroin detected in a substantial percentage of deaths (Table 2). Nearly half (45.8%) of deaths involving fentanyl analogs tested positive for two or more analogs or fentanyl, or both. Specifically, 30.9%, 51.1%, and 97.3% of deaths involving carfentanil, furanylfentanyl, and acetylfentanyl, respectively, tested positive for fentanyl or additional fentanyl analogs. Forensic investigations found evidence of injection drug use in 46.8% and 42.1% of overdose deaths involving fentanyl and fentanyl analogs, respectively. Approximately one in five deaths involving fentanyl and fentanyl analogs had no evidence of injection drug use but did have evidence of other routes of administration. Among these deaths, snorting (52.4% fentanyl and 68.8% fentanyl analogs) and ingestion (38.2% fentanyl and 29.7% fentanyl analogs) were most common. Although rare, transdermal administration was found among deaths involving fentanyl (1.2%), likely indicating pharmaceutical fentanyl (Table 2). More than one third of deaths had no evidence of route of administration."

Julie K. O’Donnell, PhD; John Halpin, MD; Christine L. Mattson, PhD; Bruce A. Goldberger, PhD; R. Matthew Gladden, PhD. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016. Morbidity and Mortality Weekly Report. Vol. 66. Centers for Disease Control. October 27, 2017.

6. Alcohol as a Factor in Overdose Deaths Attributed to Other Drugs in the US

"In 2014, alcohols, including ethanol and isopropyl alcohol, were involved in 15% of all drug overdose deaths and 17% of the drug overdose deaths that mentioned involvement of at least one specific drug. Table E shows the frequency of alcohol involvement among drug overdose deaths involving specific drugs.

"• Alcohol involvement was mentioned in 12%–22% of the drug overdose deaths involving fentanyl, heroin, hydrocodone, morphine, oxycodone, alprazolam, diazepam, or cocaine.

"• Alcohol involvement was mentioned in less than 10% of the drug overdose deaths involving methadone and methamphetamine."

Warner M, Trinidad JP, Bastian BA, et al. Drugs most frequently involved in drug overdose deaths: United States, 2010–2014. National vital statistics reports; vol 65 no 10. Hyattsville, MD: National Center for Health Statistics. 2016, pp. 5-6.

7. Worldwide Growth in Novel Psychoactive Substances

"Between 2008 and 2015, a total of 644 NPS had been reported by 102 countries and territories to the UNODC early warning advisory on NPS. The emergence of NPS was reported for the first time in 2015 in Kyrgyzstan and Mauritius. In 2015, the early warning advisory also registered the emergence of NPS in previous years in Belarus, Serbia, South Africa and Tajikistan. The majority of countries and territories that reported the emergence of NPS up to December 2015 were from Europe (41), followed by Asia (30), Africa (16), the Americas (13) and Oceania (2).
"The NPS market continues to be characterized by a large number of new substances being reported. Although data collection for 2015 is still in progress, 75 new substances have been reported to UNODC for the first time, compared with a total of only 66 in 2014. Between 2012 and 2014, most substances reported for the first time belonged to the group of synthetic cannabinoids. The data reported for 2015 so far show a different pattern: first, 20 synthetic cathinones (a group of substances with stimulant effects similar to cocaine or methamphetamine) were reported for the first time — almost as many as synthetic cannabinoids (21); and second, 21 'other substances' (substances not belonging to any of the major groups identified in previous years) were reported for the first time, including synthetic opioids (e.g. fentanyl derivatives) and sedatives (e.g. benzodiazepines).
"A growing number of NPS are reported every year by a large number of countries and territories throughout the world. NPS that have an established presence in the market include ketamine (reported by 62 countries and territories), khat (reported by 56), JWH-018 (reported by 50), mephedrone (reported by 49) and methylone (reported by 47).227 Other NPS are transient in nature and are only reported by a small number of countries and territories for a couple of years."

United Nations Office on Drugs and Crime, World Drug Report 2016 (United Nations publication, Sales No. E.16.XI.7), p. 56.

8. Rise in Opiate Prescriptions in US

"Even though opioids have been controlled in the United States with regulations and restrictions, opioid utilization has been increasing at an unprecedented pace (1-10). Manchikanti et al (1), in an evaluation of opioid usage over a period of 10 years, showed an overall increase of 149% in retail sales of opioids from 1997 to 2007 in the United States, with an increase of 1,293% for methadone, 866% for oxycodone, and 525% for fentanyl. Similarly, the increase in therapeutic opioid use in the United States in milligrams per person from 1997 to 2007 increased 402% overall, with the highest increase in methadone of 1,124% mg/person and oxycodone of 899% mg/person."

Christo,Paul J.; Manchikanti, Laxmaiah; Ruan, Xiulu; Bottros, Michael; Hansen, Hans; Solanki, Daneshvari R.; Jordan, Arthur E.; and Colson, James , "Urine Drug Testing In Chronic Pain," Pain Physician (Paducah, KY: American Society of Interventional Pain Physicians, March/April 2011), Vol. 14, Issue 2, p. 124.