Riding the Deadly Tide: Fentanyl and Stimulants Lead the Fourth Wave in U.S. Overdose Crisis

A new study reveals a 50-fold rise in US fentanylFentanyl is a synthetic opioid drug that is similar to morphine but is 50 to 100 times more potent. It is used to treat severe pain, such as pain from cancer or surgery, and is typically administered via injection or transdermal patch. Fentanyl can also be used recreationally, and its use has been linked to a significant increase in opioid overdose deaths in recent years. Due to its high potency, fentanyl can be dangerous even in small doses, and its use should be closely monitored by a healthcare provider.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>fentanyl-stimulant overdoses since 2010, marking a challenging ‘fourth wave’ in the opioid crisis, with racial disparities and regional variances in drug combinations.

New research published in the scientific journal Addiction has found that the proportion of US overdose deaths involving both fentanyl and stimulants has increased more than 50-fold since 2010, from 0.6% (235 deaths) in 2010 to 32.3% (34,429 deaths) in 2021.  By 2021, stimulants (such as cocaine and methamphetamine) had become the most common drug class found in fentanyl-involved overdoses in every US state.  This rise in fentanyl/stimulant fatalities constitutes the ‘fourth wave’ in the US’s long-running opioid overdose crisis –the death toll of which, continues to rise precipitously.

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“We’re now seeing that the use of fentanyl together with stimulants is rapidly becoming the dominant force in the US overdose crisis,” says lead author Dr. Joseph Friedman, of the University of California, Los Angeles.  “Fentanyl has ushered in a polysubstance overdose crisis, meaning that people are mixing fentanyl with other drugs, like stimulants, but also countless other synthetic substances. This poses many health risks and new challenges for healthcare providers. We have data and medical expertise about treating opioid use disorders, but comparatively little experience with the combination of opioids and stimulants together, or opioids mixed with other drugs. This makes it hard to stabilize people medically who are withdrawing from polysubstance use.”

A simplified schema of the four waves of the US overdose mortality crisis. Waves 1 and 2 include deaths involving commonly prescribed opioids, and heroin, respectively, but excluding fentanyl co-involved deaths. Wave 3 and Wave 4 show fentanyl deaths not involving, and involving, stimulants respectively as distinct trends. Data from CDC WONDER. Credit: Friedman and Shover, 2023, doi: 10.1111/add.16318

People consuming multiple substances may also be at increased risk of overdose, and many substances being mixed with fentanyl are not responsive to naloxone, the antidote to an opioid overdose.

Demographic Disparities

The authors also found that fentanyl/stimulant overdose deaths disproportionately affect racial/ethnic minority communities in the US, including Black and African American people and Native American people. For instance, in 2021, the prevalence of stimulant involvement in fentanyl overdose deaths was 73% among 65 to 74-year-old Non-Hispanic Black or African-American women living in the western US and 69% among 55 to 65-year-old Black or African-American men living in the same area.  The rate among the general US population in 2021 was 49%.

Geographical Drug Preferences

There are also geographical patterns to fentanyl/stimulant use.  In the northeast US, fentanyl tends to be combined with cocaine; in the southern and western US, it appears most commonly with methamphetamine.  Friedman says, “We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the US, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted the complete takeover by methamphetamine seen elsewhere in the country.”

The analysis illustrates how the US opioid crisis began with an increase in deaths from prescription opioids (wave 1) in the early 2000s and heroin (wave 2) in 2010.  Around 2013, an increase in fentanyl overdoses signaled the third wave.  The fourth wave – fentanyl overdoses with stimulants – began in 2015 and continues to grow.

Reference: “Charting the fourth wave: Geographic, temporal, race/ethnicity and demographic trends in polysubstance fentanyl overdose deaths in the United States, 2010–2021” by Joseph Friedman and Chelsea L. Shover, 13 September 2023, Addiction.
DOI: 10.1111/add.16318

The research was supported in part by the National Institute on Drug Abuse of the National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>National Institutes of Health under award number K01DA050771. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.