Fentanyl Deaths Seen in Emergency Departments

One of the consequences of an open Southern Border is the entrance into the U.S. of unprecedented amounts of illicit drugs.  Many of these drugs have been spiked with lethal doses of fentanyl.  Unbeknowst to the drug user, they will consume fentanyl without even knowing it.  This is the source of most accidental deaths secondary to fentanyl.  Fentanyl is the most potent of all narcotics.  On a dose:dose basis fentanyl is 50 times stronger than heroin, and 100 times stronger than morphine.  What this means is that extremely small doses of fentanyl can cause respiratory depression and death.  


The United States (US) overdose crisis has escalated in an exponential fashion for over four decades, yet with a shifting profile of drugs implicated in each successive ‘wave’ of the crisis. The first wave of the overdose crisis is typically argued to have begun in the late 1990s or early 2000s with the rise of deaths involving prescription opioids, the second wave beginning in 2010 driven by a shift to heroin, and the third wave beginning in 2013 driven by illicit fentanyl analogues. Recently, scholars have argued that the ‘fourth wave’ of the US overdose crisis has begun, in recognition of rapidly rising polysubstance overdose deaths involving illicitly manufactured fentanyls, with stimulants playing a key role. Recent studies have highlighted an increasing rate of polysubstance overdose deaths involving fentanyls and stimulants, disproportionately affecting racial/ethnic minority communities. A wide range of polysubstance formulations have been noted in drug checking and overdose mortality data, with myriad substances implicated across numerous drug classes. However, more evidence is needed about exact geographic, temporal, race/ethnicity and demographic trends, as well as which emerging polysubstance formulations are most commonly involved in fatalities.


The percent of US overdose deaths involving both fentanyl and stimulants increased from 0.6% (n = 235) in 2010 to 32.3% (34 429) in 2021, with the sharpest rise starting in 2015. In 2010, fentanyl was most commonly found alongside prescription opioids, benzodiazepines, and alcohol. In the Northeast this shifted to heroin-fentanyl co-involvement in the mid-2010s, and nearly universally to cocaine-fentanyl co-involvement by 2021. Universally in the West, and in the majority of states in the South and Midwest, methamphetamine-fentanyl co-involvement predominated by 2021. The proportion of stimulant involvement in fentanyl-involved overdose deaths rose in virtually every state 2015–2021. Intersectional group analysis reveals particularly high rates for older Black and African American individuals living in the West.


The rise of illicitly manufactured fentanyls has ushered in an overdose crisis in the United States of unprecedented magnitude. This has created conditions that have promoted a number of other shifts in the illicit drug supply, leading to rising polysubstance overdose deaths—the so-called ‘fourth wave’ of the crisis, especially involving stimulants and fentanyl co-use starting in 2015. Mixtures of fentanyl analogues and drugs of various drug classes, such as stimulants, benzodiazepines, tranquilizers and other opioids have been noted in distinct geographies.

In 2010, fentanyl was most commonly found alongside prescription medication (opioids and benzodiazepines) and alcohol (i.e. largely products produced in legal markets). Over the past decade this has shifted first to heroin-fentanyl combinations in specific states, and then universally to illicit stimulants. The fraction of all overdose deaths involving both fentanyl and stimulants grew rapidly between 2010 and 2021 and is on track to represent the single largest component of the overdose crisis in the near future. However, this has occurred in a distinct fashion based on geography and time. The northeastern states saw a period of heroin-fentanyl co-involvement, which was also found in some parts of the Midwest and South, but was completely absent from the western states (which transitioned rapidly from black tar heroin to fentanyl with methamphetamine co-involvement). By 2021, cocaine predominated in the Northeast and methamphetamine had become the most common drug found alongside fentanyls in the rest of the country.

There are now two basic archetypes of states in the United States with respect to overdose death rates: (a) states where fentanyl and cocaine co-use predominates; and (b) states where fentanyl and methamphetamine co-use predominates, with surprising little overlap between these two groups. This may reflect the combination of very low-cost, high-purity methamphetamine outcompeting cocaine and other stimulants at the national level, in addition to an enduring, well-entrenched illicit cocaine market in the Northeast and other pockets of the country.

The rise of deaths involving cocaine and methamphetamine must be understood in the context of a shifting illicit opioid drug market increasingly dominated by illicit fentanyls. Recent ethnographic and qualitative research suggests that fentanyls have created conditions that make polysubstance use more sought-after and commonplace. For instance, many individuals report that mixing a small amount of methamphetamine into injected doses of fentanyl subjectively prolongs the onset of withdrawal symptoms, increases euphoria, decreases overdose risk and improves energy levels. These perceived advantages may be particularly important given the short duration of fentanyls, requiring individuals to inject far more frequently than heroin, and the heightened overdose risk from each injection. 

Similar findings have been reported in qualitative studies of the veterinary tranquilizer, xylazine, and other drugs commonly added to fentanyls, suggesting possible structural similarities across various emerging polysubstance patterns. Given the increased risk of negative health outcomes such as overdose not fully responsive to naloxone often requiring additional life-saving measures such as airway management.

A critical consideration is the growing prevalence of counterfeit pills, which resemble psychoactive pharmaceuticals such as oxycodone or alprazolam, but contain illicit fentanyls, often mixed with other illicit substances such as stimulants, benzodiazepines, xylazine and other opioids. In recent years, counterfeit pills have grown to represent over a quarter of all illicit fentanyl seizures. Counterfeit pills have the potential to transform overdose risk as they may expand the markets for illicit synthetic drugs to subpopulations, such as adolescents, who may be less likely to consume powder fentanyl products . In the ongoing surveillance of the US overdose crisis, tracking deaths involving counterfeit pills versus other formulations represents an important dimension that is currently difficult within the existing data landscape.


By 2021 stimulants were the most common drug class found in fentanyl-involved overdoses in every state in the US. The rise of deaths involving cocaine and methamphetamine must be understood in the context of a drug market dominated by illicit fentanyls, which have made polysubstance use more sought-after and commonplace. The widespread concurrent use of fentanyl and stimulants, as well as other polysubstance formulations, presents novel health risks and public health challenges.

The information above was gleaned from a soon to be published study by Drs. Friedman and Shover. Addiction. 1-9, 2023

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