The Future of the United States Overdose Crisis: Challenges and Opportunities

Centennial Issue

Policy Points:

  • People are dying at record numbers from overdose in the United States.
  • Concerted action has led to a number of successes, including reduced inappropriate opioid prescribing and increased availability of opioid use disorder treatment and harm-reduction efforts, yet ongoing challenges include criminalization of drug use and regulatory and stigma barriers to expansion of treatment and harm-reduction services.
  • Priorities for action include investing in evidence-based and compassionate policies and programs that address sources of opioid demand, decriminalizing drug use and drug paraphernalia, enacting policies to make medication for opioid use disorder more accessible, and promoting drug checking and safe drug supply.

Substance use and overdose are major drivers of morbidity and mortality in the United States. In 2020, a national survey of households estimated that 14.5% of individuals 12 years of age and older had a substance use disorder in the past year.1 Opioid use disorder (OUD) is estimated to affect at least 1% of the US population, but assessments that adjust for underreporting in national surveys indicate the true prevalence may be nearly fivefold greater.2 OUD is particularly concerning because of the associated high risk of overdose, which is caused by respiratory depression that can occur at high doses of opioids. In the last year, ending in October of 2021, over 100,000 US deaths were caused by an overdose, of which 75% involved opioids. Overdose remains the leading cause of injury death among all age groups and the leading cause of all deaths among adults 25–44 years old.3

The overdose epidemic, which collided with the COVID-19 pandemic in 2020, has been escalating over two decades. The nature of the crisis has evolved over time, including which regions and sociodemographic groups have been most impacted, as well as the types of drugs involved.4 In the early 2000s, overdose deaths were primarily driven by rising availability of prescribed pain medications instigated by increases in pharmaceutical opioid marketing to the medical field; in the early 2010s, increased prevalence of OUD, along with a new potent supply of illicit heroin, led to increases in overdoses driven primarily by heroin; by 2013, an influx of potent synthetic opioids, including illicitly manufactured fentanyl and related analogues, began infiltrating the illicit market and drove up overdose death rates. Since 2015, overdoses have increasingly involved a combination of opioids (mostly fentanyl) with illicit stimulants such as cocaine and methamphetamine. And although earlier phases of the crisis saw sharp rises in overdose death rates among White and American Indian/Alaska Native individuals, later phases have been associated with rapidly rising death rates among Black and Hispanic individuals and sustained increases among American Indian/Alaska Native individuals.5,6

As the overdose crisis continues to escalate, we must reflect on past challenges and lessons learned so that we may develop fruitful strategies to address this epidemic in the future. In this paper, we summarize past successes, ongoing challenges, and potential solutions to address substance use and overdose in the context of primary, secondary, and tertiary prevention efforts.We then discuss implications for broader policy, training, and leadership in the field that could address current and future substance use crises in the United States and beyond.


  1. Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results from the 2020 National Survey on Drug Use and Health. HHS Publication No. PEP20-07-01-001, NSDUH Series H-55. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration; 2020.
  2. Keyes K, Rutherford C, Hamilton A, et al. What is the prevalence of and trend in opioid use disorder in the United States from 2010 to 2019? Using multiplier approaches to estimate prevalence for an unknown population size. Drug Alcohol Depend Rep. 2022;3:100052.
  3. WISQARS Data Visualization: 10 Leading Causes of Death, United States 2020, Both Sexes, All Ages, All Races. CDC National Center for Injury Prevention and Control. 2022. Accessed March 27, 2022.
  4. Cerdá M, Krawczyk N, Hamilton L, Rudolph KE, Friedman SR, Keyes KM. A critical review of the social and behavioral contributions to the overdose epidemic. Annu Rev Public Health. 2021;42(1):95-114.
  5. Friedman J, Beletsky L, Jordan A. Surging racial disparities in the U.S. overdose crisis. Am J Psychiatry. 2022;179(2):166-169.
  6. Hedegaard H, Miniño A, Spencer MR, Warner M. Drug overdose deaths in the United States, 1999–2020. NCHS Data Brief. 2021;(426):1-8.

Cerdá M,Krawczyk N, Keyes K. The Future of the United States Overdose Crisis: Challenges and Opportunities. Milbank Q. 2023;101(S1): 478-506.