"• The rate of drug overdose deaths involving synthetic opioids other than methadone, which include drugs such as fentanyl, fentanyl analogs, and tramadol, increased from 0.3 per 100,000 in 1999 to 1.0 in 2013, 1.8 in 2014, 3.1 in 2015, 6.2 in 2016, and 9.0 in 2017 (Figure 4). The rate increased on average by 8% per year from 1999 through 2013 and by 71% per year from 2013 through 2017.

"• The rate of drug overdose deaths involving heroin increased from 0.7 in 1999 to 1.0 in 2008 to 4.9 in 2016. The rate in 2017 was the same as in 2016 (4.9).

According to the Centers for Disease Control, using data available for analysis on September 5, 2018, there were a reported 70,652 deaths attributed to drug overdose in the US for the year ending December 2017. Some deaths were still under investigation. The CDC projects that the total for 2017 will be 72,222.

"Since 2012, a total of 28 new fentanils have been identified on Europe’s drug market. This includes eight substances that were reported for the first time in 2016 and 10 during 2017. During this period, there has also been a large increase in seizures reported by customs at international borders and police at street-level (Figure 4) (see also ‘Reducing the risk of occupational exposure to fentanils’, page 11). While the picture differs widely across Europe, 23 countries have reported detections of one or more of these substances (Figure 5) (2).

"Alongside their legitimate uses as medicines and in research, the fentanils also have a long history of illicit use as replacements for heroin and other controlled opioids. Between 1979 and 1988, more than 10 fentanils that had been made in illicit laboratories were detected on the drug market in the United States (Henderson, 1991). The first was alpha-methylfentanyl, followed by substances such as 3-methylfentanyl and 4-fluorofentanyl. Typically, they were sold as heroin or ‘synthetic heroin’.

"With a total of 38 different opioids reported, the number of synthetic opioids has grown rapidly in Europe since the first substance was reported in 2009. In fact, most of these substances have been reported for the first time during the past two years, with 9 reported in 2016 and 13 during 2017.

According to the US 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.

"• In 2017, there were 70,237 drug overdose deaths in the United States.

"• The age-adjusted rate of drug overdose deaths in 2017 (21.7 per 100,000) was 9.6% higher than the rate in 2016 (19.8).

"• Adults aged 25–34, 35–44, and 45–54 had higher rates of drug overdose deaths in 2017 than those aged 15–24, 55–64, and 65 and over.

"• West Virginia (57.8 per 100,000), Ohio (46.3), Pennsylvania (44.3), and the District of Columbia (44.0) had the highest age-adjusted drug overdose death rates in 2017.

"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.

"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).

"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.