"• 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.

"We contribute nationally representative evidence to help answer each of these questions, including wholesale pricing data from a proprietary drug sales database spanning January 2006 to February 2017. We find that all formulations of naloxone increased in price since 2006 except for Narcan Nasal Spray. These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 MG Evzio auto-injector.

"The US Drug Enforcement Administration introduced a schedule change for hydrocodone combination products in October 2014. During the period of our study, October 2013 to July 2016, the percentage of total drug sales represented by prescription opioids in the US doubled from 6.7% to 13.7%, which corresponds to a yearly increase of 4 percentage points in market share. It is not possible to determine the location of buyers from cryptomarket data. We cannot know, for example, if a drug shipped from a vendor in Europe was purchased by a US customer.

"Vulnerability to Opioid Overdose

"Of the 1,000,453 opioid recipients (81.7%) with at least 6 months of follow-up, 51.1% were female, and the median age was 17 years (interquartile range, 16-18 years). Among these adolescents, the estimated cumulative incidence of LTOT [Long Term Opioid Therapy] after first opioid receipt was 1.1 (95% CI, 1.1-1.2) per 1000 recipients within 1 year, 3.0 (95% CI, 2.8-3.1) per 1000 recipients within 3 years, 8.2 (95% CI, 7.8-8.6) per 1000 recipients within 6 years, and 16.1 (95% CI, 14.2-18.0) per 1000 recipients within 10 years.

"In this nationwide study of commercially insured adolescents, LTOT [Long Term Opioid Therapy] was relatively uncommon. The estimated incidence of LTOT receipt was 3.0 per 1000 adolescents within 3 years of filling an initial opioid prescription. Although adolescents with a wide range of preexisting mental health conditions and treatments were modestly more likely than adolescents without those conditions or treatments to receive an initial opioid, the former had substantially higher rates of subsequent transitioning to LTOT.

"Over the 15-year study period, 335,123 opioid-related deaths in the United States met our inclusion criteria, with an increase of 345% from 9489 in 2001 (33.3 deaths per million population) to 42,245 in 2016 (130.7 deaths per million population). By 2016, men accounted for 67.5% of all opioid-related deaths (n = 28,496), and the median (interquartile range) age at death was 40 (30-52) years.

According to the United Nations Office on Drugs and Crime:

In the United States in 2015 (the most recent year for which data are available), the retail price of black tar heroin ranged from $20 to $300 per gram; the retail price of South American heroin ranged from $25 to $400 per gram; and the retail price of southwest Asian heroin ranged from $120 to $300 per gram.

In Canada in 2014 (the most recent year for which data are available), the retail price of opium ranged from $43 to $55.90 per gram; and the retail price of heroin ranged from $154.80 to $300.90 per gram.

According to the United Nations Office on Drugs and Crime:

In the United States in 2015 (the most recent year for which data are available), the wholesale price of black tar heroin ranged from $12,000 to $100,000 per kilogram; the wholesale price of South American heroin ranged from $10,000 to $100,000 per kilogram and the price of southwest Asian heroin ranged from $50,000 to $85,000 per kilogram.

In Mexico in 2015 (the most recent year for which data are available), the wholesale price of heroin was $35,000 per kilogram.