The trend marks the fourth wave in the United States’ overdose crisis, which began with deaths from prescription opioids in the early 2000s and has since continued with other drugs.
New research led by UCLA has found that the proportion of overdose deaths in the United States 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 class of drugs found in fentanyl-related overdoses in all US states. This increase in fentanyl /stimulant deaths constitutes the “fourth wave” of the prolonged opioid overdose crisis in the United States, whose death toll continues to skyrocket.
"We are now seeing that the use of fentanyl along with stimulants is rapidly becoming the dominant force in the overdose crisis in the United States," said lead author Joseph Friedman, an additional investigator at the David Geffen School of Medicine at UCLA. “Fentanyl has caused a multi-substance overdose crisis, meaning people mix fentanyl with other drugs , such as stimulants, but also with many other synthetic substances. This poses many health risks and new challenges for healthcare providers. We have data and medical experience on the treatment of opioid use disorders, but comparatively little experience with combining opioids and stimulants together, or with opioids mixed with other drugs. “This makes it difficult to medically stabilize people who are quitting polysubstance use.”
The findings are published in the peer-reviewed journal Addiction .
The analysis illustrates how the opioid crisis in the United States began with a rise in deaths from prescription opioids (wave 1) in the early 2000s and from heroin (wave 2) in 2010. Around 2013, a rise in Fentanyl overdose marked the third wave. The fourth wave (fentanyl overdose with stimulants) began in 2015 and continues to grow.
Figure : Four waves of overdose mortality. A simplified outline of the four waves of the overdose mortality crisis in the United States. Waves 1 and 2 are represented by deaths related to commonly prescribed opioids and heroin, respectively, but excluding fentanyl-related deaths. Fentanyl-related deaths are excluded here for illustrative purposes because the precipitous increase in fentanyl-related deaths starting in 2013 has had the effect of increasing death rates from a large number of other substances used in conjunction with fentanyls, despite the fact that fentanyls represent the main cause. factor in waves 3 and 4. Here, we can see that the waves driven by prescription opioids and heroin reach inflection points and begin to decline in 2010 and 2015 respectively, after removing the inflationary effects of the co-involvement of fentanyl. Waves 3 and 4 are separated by showing non-stimulant and stimulant-involving fentanyl deaths, respectively, as distinct trends, revealing the brief ~2-year lag between the two waves. Data were obtained from the Centers for Disease Control and Prevention’s extensive online database for epidemiologic research.
To further complicate matters, people who use polysubstances may also be at higher risk of overdose, and many substances mixed with fentanyl do not respond to naloxone , the antidote to an opioid overdose.
The authors also found that fentanyl/stimulant overdose deaths disproportionately affect racial/ethnic minority communities in the US, including Blacks, African Americans, and Native Americans. For example, in 2021, the prevalence of stimulant involvement in fentanyl overdose deaths was 73% among non-Hispanic black or African American women aged 65 to 74 years living in the Western US and 69% among women aged 55 to 65 years. The rate among the general US population in 2021 was 49%.
There are also geographic patterns in fentanyl/stimulant use . In the northeastern United States, fentanyl tends to be combined with cocaine ; in the southern and western US, it appears most commonly with methamphetamine .
“We suspect that this pattern reflects the increasing availability and preference for low-cost, high-purity methamphetamine throughout the United States, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted complete meth takeover has been seen in other parts of the country,” Friedman said.
Conclusions We provide a detailed overview of the fourth wave of the overdose crisis in the United States, characterized by a sharp increase in polysubstance overdose deaths related to illicitly manufactured fentanyls. The co-involvement of stimulants and fentanyl is quickly becoming the most important component of the crisis, with a distinct pattern seen over time and across geography and sociodemographic groups. The regional pattern of cocaine-fentanyl in the Northeast and methamphetamine-fentanyl in the rest of the country is particularly notable. The widespread simultaneous use of fentanyl and stimulants, as well as other polysubstance formulations, presents numerous novel health risks and public health challenges. Going forward, continued and nuanced surveillance is needed to track this rapidly changing phenomenon. |
Final message
In 2021, stimulants were the most common class of drug found in fentanyl-related overdoses in every US state. The increase in cocaine and methamphetamine-related deaths must be understood in the context of a dominated drug market by illicit fentanyls, which have made the consumption of polysubstances more sought after and common. The widespread simultaneous use of fentanyl and stimulants, as well as other polysubstance formulations , presents new health risks and challenges to public health.
The study was funded by the UCLA Medical Scientist Training Program (National Institute of General Medical Sciences training grant GM008042) and the National Institute on Drug Abuse of the National Institutes of Health (K01DA050771). The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
