The Evolving Overdose Crisis: United States Needs Robust Policy Change to Address the Fourth Wave

After a year-over-year increase since 2018, the United States saw a small dip in overdose deaths in 2023. Despite this slight reduction in fatal overdoses, driven primarily by fewer deaths caused by opioids, deaths from stimulants like amphetamines and cocaine increased, and some communities across the country suffered significantly more overdoses than in 2022.¹ Specifically, fatal overdose rates among non-Hispanic Black, Native Hawaiian, and other Pacific Islander populations rose dramatically during this time period.¹ In addition, newer substances like nitazenes, xylazine, and novel fentanyl analogs are rapidly entering the drug supply across the country, with each region of the United States experiencing these changes differently.^2,3

Rather than view the small overall reduction in overdoses as a sign that the crisis is abating, many experts believe we have entered the fourth “wave” of the 21st century overdose crisis.⁴ This wave is marked by polysubstance use—specifically, the use of both fentanyl and stimulants. In this issue, Diekhans et al. (p. 555) describe a study that analyzed drug residue and paraphernalia found at the scenes of fentanyl-involved fatal overdoses in San Francisco, California, in 2022. Their findings add to a growing body of evidence supporting an evolving drug supply, an increase in stimulant-involved fatal overdoses, and a shift among some people who use drugs toward different modes of use beyond injection.

THE CHANGING DRUG SUPPLY

The US drug supply is heterogeneous. Previous research highlights how fentanyl and xylazine first emerged on the East Coast before making their way west.^2,5 For example, we conduct research in Philadelphia, Pennsylvania, a city where new trends in the drug supply often emerge. The city’s opioid supply shifted almost completely from heroin to fentanyl by 2015. Newer substances in the local supply include medetomidine—similar to but more potent than xylazine—and the sedative etomidate, and 99% of the street opioid supply contained xylazine in the first half of 2023.^6,7 By contrast, Diekhans et al. found xylazine in only 10% of their study’s included cases in San Francisco and a stimulant supply of methamphetamine and cocaine. In their study, methamphetamine was typically found alone, whereas cocaine was detected more frequently alongside fentanyl.

These trends and differences have important implications for public health responses. The United States has not systematically invested in scaled-up drug checking, obscuring the data needed to implement public health interventions. These data are critical on two fronts: to aggregate results to better understand a comprehensive picture of the composition of a locality’s drug supply and to provide real-time data to people who use drugs about the drugs they are buying and using so they can make more informed decisions about their use.

In addition to supporting the assertion that the overdose crisis is now in its fourth wave, the findings from Diekhans et al. also underscore how our policy responses to the constantly evolving crisis are often a step behind. Information about the drug supply notwithstanding, drug use patterns are driven at least in part by the unregulated supply of drugs even when some information about the supply is known. The authors note that more than half of overdose decedents in their included cases test positive for at least one stimulant in addition to fentanyl. This is a noteworthy hallmark of the fourth wave of the overdose crisis and mirrors trends of polysubstance use and overdoses seen across the country.¹

Likewise, some preliminary data from our research in Philadelphia indicate that more people are using stimulants to counter the sedating impacts of xylazine. Increased stimulant use is especially pronounced among unhoused people who use drugs, a population more structurally vulnerable to both violence while sedated and fatal overdoses. Polysubstance use of stimulants and opioids requires a different treatment approach than that for solely opioids.⁴ For example, there is no gold-standard medication treatment of stimulant-use disorders as there is for opioid use disorder. Research about effective treatment of polysubstance use lags that of opioids alone, and current regulations inhibit the accessibility of an evidence-based behavioral treatment of stimulant use disorder.⁴ As long as the drug supply continues to be unregulated, drug-related morbidity and mortality will remain elevated, and their patterns will shift ahead of our ability to have robust public health and treatment responses.

SHIFTS IN ROUTES OF ADMINISTRATION

Finally, this study adds to the body of evidence reporting a shift toward smoking and snorting among many people who use drugs, which may offer some (although in many cases not sufficient) protection from overdose and skin and soft tissue infections.^8,9 People who choose smoking or snorting instead of injecting report making the change in an attempt to mitigate risks in the face of an increasingly unpredictable drug supply and, in some cases, because the drug supply has already led to wounds and scarring that have made injection more difficult.⁸

Given this shift, it is imperative that harm reduction programs are able to offer appropriate supplies, and providing alternatives to injection—like pipes and other smoking and snorting equipment—may increase participant engagement with the litany of services these programs provide, including overdose prevention resources such as naloxone distribution.¹⁰ Unfortunately, safer smoking supplies are notoriously difficult for many programs to obtain given a ban on using federal funds to cover distribution,¹¹ and harm reduction programs have faced increasing scrutiny and pushback despite strong evidence that they provide a litany of vital services including overdose reversal, wound care, and opioid use disorder treatment.¹² While the findings of this study and many others highlight the need for expanded harm reduction services, these programs and other evidence-based substance use disorder interventions are increasingly under attack.¹²

As highlighted recently by this journal, the impacts of the overdose crisis are far reaching; more than 1.4 million US children have lost a family member.¹³ Despite headlines celebrating a small dip in fatal overdoses, the yearly death toll remains shockingly and unacceptably high. Until we take pragmatic action, which should include all evidence-based approaches including overdose prevention sites, expanding available medications for opioid use disorder, investing in effective treatments for stimulant and polysubstance use disorders, and exploring options for a safer supply of substances, we will not be able to make substantial progress in stemming the overdose crisis and improving the health outcomes of people who use drugs.