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Synthetic Opioid Overdose Data

Synthetic opioids are a class of drugs that are designed to provide pain relief, mimicking naturally occurring opioids such as codeine and morphine. They tend to be highly potent, which means only a small amount of the drug is required to produce a given effect. They include drugs like tramadol and fentanyl. Methadone is also a synthetic opioid; however, deaths involving this drug are tracked separately from deaths involving other synthetic opioids, particularly in National Vital Statistics System data.

Although synthetic opioids are manufactured by pharmaceutical companies, they are also manufactured illegally in clandestine labs and distributed through the illicit drug market. Deaths involving pharmaceutical and illicit synthetic opioids cannot be distinguished in National Vital Statistics System data.

What is Fentanyl?

Fentanyl is a synthetic (man-made) opioid 50 times more potent than heroin and 100 times more potent than morphine. There are two types of fentanyl:

  • Pharmaceutical fentanyl is primarily prescribed to manage severe pain, such as with cancer and end-of-life palliative care.
  • Non-pharmaceutical fentanyl is frequently referred to as illicitly manufactured fentanyl (IMF). IMF is often mixed with heroin and/or cocaine or pressed into counterfeit pills—with or without the user’s knowledge.

Overdose Deaths Involving Synthetic Opioids

Death rates involving synthetic opioids (other than methadone), which include drugs such as tramadol and fentanyl, doubled from 2015 to 2016.

  • In 2016, more than 19,000 deaths involving synthetic opioids (other than methadone) occurred in the United States, which is more deaths than from any other type of opioid.
  • Also in 2016, the largest increase in synthetic opioid overdose death rates was in persons aged 25-44, specifically males aged 25-44.
  • Deaths from synthetic opioids significantly increased in 21 states, with rates at least doubling in 10 states, from 2015 to 2016. New Hampshire, West Virginia, and Massachusetts had the highest death rates from synthetic opioids.1

Synthetic opioid overdose death rates (other than methadone) increased across all demographics, regions, and numerous states. State reports have indicated that increases in synthetic opioid-involved deaths have been associated with the number of drug submissions obtained by law enforcement that test positive for fentanyl but not with fentanyl prescribing rates. These reports indicate that increases in synthetic opioid-involved deaths are being driven by increases in fentanyl-involved overdose deaths, and the source of the fentanyl is more likely to be illicitly manufactured than pharmaceutical.2,3,4

There are also fentanyl analogs, such as acetylfentanyl, furanylfentanyl, and carfentanil, which are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Recent surveillance has also identified other emerging synthetic opioids, like U-47700.5 Estimates of the potency of fentanyl analogs vary from less potent than fentanyl to much more potent than fentanyl, but there is some uncertainty because potency of illicitly manufactured fentanyl analogs has not been evaluated in humans. Carfentanil, the most potent fentanyl analog detected in the U.S., is estimated to be 10,000 times more potent than morphine. 5,6

  • Large central metro—Counties in metropolitan statistical areas of 1 million or more population that:
    • Contain the entire population of the largest principal city
    • Have their entire population contained in the largest principal city
    • Contain at least 250,000 inhabitants of any principal city
  • Large fringe metro—Counties of 1 million or more population that did not qualify as large central metro counties.
  • Medium metro—Counties of populations of 250,000 to 999,999.
  • Small metro—Counties of populations less than 250,000.
  • Micropolitan—Counties in micropolitan statistical areas that have a population of at least 10,000 but less than 50,000.
  • Noncore—Nonmetropolitan counties that did not qualify as micropolitan.


Categories of 2013 NCHS Urban-Rural Classification Scheme for Counties (


Age-adjusted death rates for synthetic opioids are plotted above by urbanization classification of residence for 2015 to 2016. Rates increased significantly for all areas – large central metro (141.7%), large fringe metro (110.3%), and medium metro (80.0%), small metro (88.0%), micropolitan (66.7%), and noncore (57.7%) areas. The synthetic opioid overdose death rate also increased in the United States overall—a statistically significant 100.0% increase from 2015 to 2016, with a total of 19,413 deaths in 2016. Deaths are classified using the International Classification of Diseases, Tenth Revision (ICD–10). Drug overdose deaths are identified using underlying cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14. Drug overdose deaths, as defined, that have synthetic opioids other than methadone (T40.4) as a contributing cause. Age-adjusted death rates were calculated using the direct method and the 2000 standard population.1


  1. Seth P, Scholl L, Rudd RA, Bacon S. Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants – United States, 2015-2016. MMWR Morb Mortal Wkly Rep. March 2018.67(12);349–358.
  2. Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions and increases in synthetic opioid-Involved overdose deaths – 27 states, 2013-2014. Morb Mortal Wkly Rep. 2016;65(33):837-43.
  3. Peterson AB, Gladden RM, Delcher C, Spies E, Garcia-Williams A, Wang Y, et al. Increases in fentanyl-related overdose deaths – Florida and Ohio, 2013-2015. Morb Mortal Wkly Rep. 2016;65(33):844-9.
  4. O’Donnell JK, Gladden RM, Seth P. Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region — United States, 2006–2015. MMWR Morb Mortal Wkly Rep 2017;66:897–903.
  5. O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016. MMWR Morb Mortal Wkly Rep 2017;66:1197–1202.
  6. O’Donnell J, Gladden RM, Mattson CL, Kariisa M. Notes from the Field: Overdose Deaths with Carfentanil and Other Fentanyl Analogs Detected – 10 States, July 2016-June 2017. MMWR Morb Mortal Wkly Rep. July 2018. 67(27);767–768.