Fentanyl-Laced Stimulants Fuel Opioid Crisis' Fourth Wave

Megan Brooks

September 15, 2023

Drug overdose deaths in the US involving both fentanyl and stimulants have increased more than 50-fold since 2010 and accounted for 32% of US fatal overdoses in 2021, new research shows.

The rise in fentanyl-stimulant fatalities constitutes the "fourth wave" in the long-running opioid overdose crisis, which began with an increase in deaths from prescription opioids in the early 2000s (wave 1) and heroin (wave 2) in 2010.

Around 2013, an increase in fentanyl overdoses signaled the third wave. This was followed in 2015 by sharply rising polysubstance overdose deaths involving illicitly manufactured fentanyls.

The use of fentanyl together with stimulants is "rapidly becoming the dominant force in the US overdose crisis," lead author Joseph Friedman, PhD, MPH, from UCLA's Center for Social Medicine and Humanities, Los Angeles, said in a news 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," said Friedman.

The study was published online September 14 in the journal Addiction.

"Alarming" Data

The researchers analyzed national death certificate data for all people who died from drug overdose in the US from 2010 to 2021.

The percentage of overdose deaths in that 12-year span involving both fentanyl and stimulants jumped from 0.6% (235 deaths) in 2010 to 32.3% (34,429 deaths) in 2021, they report.

"This reflects intentional co-use (for example, using fentanyl and methamphetamine together) and unintentionally using fentanyl and stimulants," senior investigator Chelsea L. Shover, PhD, with UCLA, told Medscape Medical News.

Shover said it's hard to tell from the data how much is intentional and how much is unintentional, but based on other research she's done, she would attribute most to intentional co-use.

Fentanyl/stimulant overdose deaths disproportionately affect racial/ethnic minority communities in the US, including Black and African American people and Native American people, the data show.

And there are "notable" geographic patterns to fentanyl/stimulant use. In the Northeast US, fentanyl tends to be combined with cocaine, while in the southern and western US, it appears most commonly with methamphetamine.

Rapidly Shifting Trends

"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 said in the release.

The authors note that the landscape of polysubstance overdose has been evolving in a "highly rapid manner. Therefore, even the most current results may simply represent snapshots of shifting dynamics that will soon change."

The numbers in this report are "alarming," Nora Volkow, MD, director of the National Institute on Drug Abuse, who wasn't involved in the study, told Medscape Medical News.

"What's very concerning is that [overdose deaths] are not going down as we emerge from the pandemic period as I was expecting," Volkow said.

"Another alarming trend," said Volkow, is the increasing black-market sale of counterfeit prescription pills that are laced with illicit fentanyls and often mixed with other illicit substances such as stimulants, benzodiazepines, xylazine, and other opioids.

Volkow said studies like this are "important" to stay on top of shifting trends and what drugs are coming into the country because they are constantly changing.

"What was true, for example, even 3 years ago, may not be very relevant now, particularly when you consider the tremendous heterogeneity across the United States," said Volkow.

The study was funded by the UCLA Medical Scientist Training Program (National Institute of General Medical Sciences training grant) and the National Institute on Drug Abuse. Friedman, Shover and Volkow report no relevant financial relationships.

Addiction. Published online September 14, 2023. Full text

For more Medscape Psychiatry news, join us on Twitter and Facebook


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.