Unprecedented Spike in Fentanyl-Infused Stimulant Fatalities Marks the 4th Wave of the U.S. Overdose Crisis

The latest trend marks the fourth wave in the ongoing overdose crisis in the United States. This crisis originally began with prescription opioid-related deaths in the early 2000s and has continued to evolve with the involvement of various drugs. A recent study led by UCLA reveals a startling increase of over 50 times in the proportion of overdose deaths in the US involving both fentanyl and stimulants since 2010. In 2010, only 0.6% (235 deaths) of overdose cases were attributed to this combination, but by 2021, it had risen to a staggering 32.3% (34,429 deaths). By 2021, stimulants such as cocaine and methamphetamine had become the most prevalent drug class associated with fentanyl-related overdoses in every US state. This alarming surge in fentanyl and stimulant-related fatalities represents the ‘fourth wave’ in the ongoing opioid overdose crisis, with the death toll continuing to rise sharply.

Lead author Joseph Friedman, an addiction researcher at the David Geffen School of Medicine at UCLA, noted, “We’re now witnessing the rapid emergence of fentanyl combined with stimulants as the dominant force in the US overdose crisis. Fentanyl has introduced a complex challenge of polysubstance overdose, where individuals are combining fentanyl with not only stimulants but also numerous other synthetic substances. This presents significant health risks and new complexities for healthcare providers. While we have data and medical expertise in treating opioid use disorders, we have comparatively limited experience in dealing with the combination of opioids and stimulants or opioids mixed with other substances. This makes it difficult to provide effective medical stabilization for individuals withdrawing from polysubstance use.”

The study’s findings were published in the peer-reviewed journal Addiction on September 13.

The timeline of the opioid crisis in the US can be divided into four waves. It began with a surge in deaths related to prescription opioids in the early 2000s (wave 1) and heroin in 2010 (wave 2). Around 2013, an increase in fentanyl-related overdoses marked the third wave. The fourth wave, characterized by fentanyl overdoses in conjunction with stimulants, commenced in 2015 and continues to escalate.

Complicating matters further is the heightened risk of overdose among individuals consuming multiple substances. Additionally, many of the substances mixed with fentanyl do not respond to naloxone, the antidote used for opioid overdoses.

The study also revealed demographic and geographical disparities in fentanyl/stimulant overdose deaths. These deaths disproportionately affect racial and ethnic minority communities, including Black and African American populations and Native American communities. For instance, in 2021, stimulant involvement in fentanyl overdose deaths was as high as 73% among Non-Hispanic Black or African-American women aged 65 to 74 in the western US and 69% among Black or African-American men aged 55 to 65 in the same region, compared to the national average of 49%.

Geographical patterns were observed as well, with fentanyl commonly combined with cocaine in the northeastern US, while in the southern and western US, it was most frequently associated with methamphetamine. This pattern is believed to reflect the increased availability and preference for low-cost, high-purity methamphetamine across the country, as well as regional differences in illicit cocaine use.

The study received funding from the UCLA Medical Scientist Training Program and the National Institute on Drug Abuse at the National Institutes of Health. The authors emphasize that the views expressed in the study are solely their responsibility and do not necessarily represent the official views of the National Institutes of Health.

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