Healthcare, opioid epidemic and drug abuse concept with the map of USA filled with oxycodone and hydrocodone pharmaceutical pills on the American flag

(© Victor Moussa -

LOS ANGELES — Fentanyl, an extremely potent synthetic opioid, is roughly 100 times more powerful than morphine and 50 times stronger than heroin. While technically approved by the U.S. Food and Drug Administration (FDA) to treat pain and serve as an anesthetic under the right medical conditions, fentanyl’s recent emergence as a street drug has exasperated and worsened the ongoing opioid crisis in the United States. Now, researchers from the University of California-Los Angeles report U.S. overdose deaths involving both fentanyl and stimulants have increased by more than 50-fold over the past 13 years.

In 2010, health officials tied 235 deaths (0.6%) to a mixture of fentanyl and stimulants. In 2021, that number rose to 34,429 deaths (32.2%).

In fact, by 2021, stimulants like cocaine and methamphetamine became the most common types of drugs found in fentanyl-involved overdoses across every single U.S. state. This troubling rise in deaths tied to fentanyl and stimulants represents the fourth wave of America’s long-running opioid overdose crisis, researchers explain.

The opioid crisis in the United States has persisted now for roughly two decades, taking the lives of over half a million Americans along the way. The astounding staying power and longevity of the crisis are startling to consider at first, but it’s key to understand that opioid-related overdoses have come in a series of distinct waves since around the turn of the 21st century.

Opioids, medicine bottle with pills
(© Kimberly Boyles –

Starting in the early 2000s, researchers noted a spike in deaths in connection to prescription opioids (wave 1). By 2010, the number of fatal overdoses tied to heroin was skyrocketing (wave 2). By 2013, fentanyl overdoses began to dominate reported drug fatalities (wave 3). Just a few years later (2015), deaths attributed to fentanyl overdoses with stimulants began to appear more and more, with this trend continuing to grow today (wave 4).

“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 Joseph Friedman, an addiction researcher at the David Geffen School of Medicine at UCLA, in a media release. “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.”

Of course, it’s key to mention that anyone who consumes multiple substances in a short period may be at an increased risk of overdose. Even worse, many substances known to be mixed with fentanyl are not responsive to naloxone, considered the antidote to an opioid overdose.

Researchers also note that fentanyl/stimulant overdose deaths appear to disproportionately occur among racial and ethnic minority communities in the United States (African Americans, Native Americans). For example, in 2021 the rate of stimulant involvement in fentanyl overdose deaths was 73 percent for 65 to 74-year-old non-Hispanic Black or African American women living in the western United States. That same prevalence was 69 percent among 55 to 65-year-old Black or African-American men living in the same place. In 2021, prevalence in the entire U.S. population was 49 percent.

Geographical patterns also appear relevant to this topic. In the northeastern United States, fentanyl is typically combined with cocaine, whereas in the southern and western U.S., it is more commonly mixed with a form of methamphetamine.

“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,” Friedman concludes.

The study is published in the journal Addiction.

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