Deadly Fourth Wave: Fentanyl and Stimulant Overdoses Surge in America

A fentanyl-stimulant overdose wave claimed more than 34,000 lives in 2021, a study finds, highlighting the need for more available evidence-based treatments for substance use disorders.

The proportion of overdose deaths involving both fentanyl and stimulants has increased from 0.6% (235 deaths) in 2010 to 32.3% (34,429 deaths) in 2021 in the United States according to a new study published in the journal Addiction.

By 2021, stimulants, such as cocaine and methamphetamine, had become the most common drug class in overdoses involving fentanyl in every U.S. state, constituting the "fourth wave" in the opioid overdose crisis.

Researchers say that people mix fentanyl not only with other drugs, like stimulants but also 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.

- Lead author Joseph Friedman of the University of California, Los Angeles

Mixing fentanyl with multiple substances may increase the risk of overdose because they are not responsive to naloxone, the antidote to an opioid overdose.

Chelsea Shover, the study's co-author and assistant professor-in-residence at the UCLA School of Medicine, emphasizes that naloxone still works on fentanyl, even if it is mixed with other drugs.

"Always give naloxone for suspected overdose, but the presence of other drugs might mean the person requires other supportive care like oxygen. Naloxone administered in time can make the difference between life and death. Opioids generally cause death by respiratory depression. Stimulants like cocaine or methamphetamine cause death in different ways, often by exacerbating underlying conditions like heart disease," she told Healthnews.

Shover says that overdoses involving stimulants and opioids also underline the need to address other health problems that people who use both may have.

Minorities are most affected by drug overdoses

The study shows that deaths caused by fentanyl-stimulant overdose wave disproportionately affect racial/ethnic minority communities, such as 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 U.S. and 69% among 55 to 65-year-old Black or African-American men living in the same area. In comparison, the rate among the general U.S. population in 2021 was 49%.

The study also reveals geographical patterns in the use of both fentanyl and stimulants. In the Northeast, for example, fentanyl is often combined with cocaine, whereas in the southern and western U.S., it tends to be mixed with methamphetamine.

"We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the U.S., 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 adds.

The first wave of the U.S. opioid overdose crisis began with increased deaths from prescription opioids in the early 2000s, whereas rising deaths from heroin overdose in 2010 marked the second wave. Around 2013, an increase in fentanyl overdoses caused the third wave. Fentanyl-stimulant overdose wave, known as the fourth wave, began in 2015 and continues to grow.

Shover says the study results highlight the importance of making evidence-based treatment for substance use disorders more available across the U.S.

"That includes medication for opioid use disorder and contingency management for stimulant use disorder. It's also important to find ways to provide better treatment for people with co-occurring substance use disorders," she said.

Fentanyl is a synthetic opioid that is up to 50 times stronger than heroin and 100 times stronger than morphine, according to the Centers for Disease Control and Prevention (CDC).

Pharmaceutical fentanyl is prescribed by doctors to treat severe pain, such as after surgery or advanced-stage cancer. However, most recent overdose cases are linked to fentanyl which is made and distributed illegally.