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.

"First, factors related to death investigation might affect rate estimates involving specific drugs. At autopsy, the substances tested for, and circumstances under which tests are performed to determine which drugs are present, might vary by jurisdiction and over time. Second, the percentage of deaths with specific drugs identified on the death certificate varies by jurisdiction and over time. Nationally, 19% (in 2014) and 17% (in 2015) of drug overdose death certificates did not include the specific types of drugs involved.

"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."

"A key factor underlying the recent increases in rates of heroin use and overdose may be the low cost and high purity of heroin.^45,46 The price in retail purchases has been lower than $600 per pure gram every year since 2001, with costs of $465 in 2012 and $552 in 2002, as compared with $1237 in 1992 and $2690 in 1982.⁴⁵ A recent study showed that each $100 decrease in the price per pure gram of heroin resulted in a 2.9% increase in the number of hospitalizations for heroin overdose.⁴⁶"

"In 2016, a total of 67,265 persons died of drug-induced causes in the United States (Tables 5, 6, 8, and I–1). This category includes deaths from poisoning and medical conditions caused by use of legal or illegal drugs, as well as deaths from poisoning due to medically prescribed and other drugs. It excludes deaths indirectly related to drug use, as well as newborn deaths due to the mother's drug use. (For a list of drug-induced causes, see Technical Notes.)

Cannabis and Mortality: "In summary, this study showed little, if any, effect of marijuana use on non-AIDS mortality in men and on total mortality in women. The increased risk of AIDS mortality in male marijuana users probably did not reflect a causal relationship, but most likely represented uncontrolled confounding by male homosexual behavior. The risk of mortality associated with marijuana use was lower than that associated with tobacco cigarette smoking."

Estimated Annual Number of Deaths Caused by Tobacco Use in the US: "The 2014 Surgeon General's report estimates that cigarette smoking causes more than 480,000 deaths each year in the United States.¹ This widely cited estimate of the mortality burden of smoking may be an underestimate, because it considers deaths only from the 21 diseases that have been formally established as caused by smoking (12 types of cancer, 6 categories of cardiovascular disease, diabetes, chronic obstructive pulmonary disease [COPD], and pneumonia including influenza).

Increasing Involvement Of Benzodiazepines In Opioid Overdose Mortality In The US, 2011: "In 2011, 5,188 opioid-analgesic poisoning deaths also involved benzodiazepines (sedatives used to treat anxiety, insomnia, and seizures), up from 527 such deaths in 1999 (Figure 3). From 2006 through 2011, the number of opioid-analgesic poisoning deaths involving benzodiazepines increased 14% on average each year, while the number of opioid-analgesic poisoning deaths not involving benzodiazepines did not change significantly."

"Naloxone distribution to heroin users would be expected to reduce mortality and be cost-effective even under markedly conservative assumptions of use, effectiveness, and cost. Although the absence of randomized trial data on naloxone distribution and reliance on epidemiologic data increase the uncertainty of results, there are few or no scenarios in which naloxone would not be expected to increase QALYs [Quality-Adjusted Life-Years] at a cost much less than the standard threshold for cost-effective health care interventions.