Polysubstance involvement in youth opioid overdoses increases with age

Most research suggests that opioid overdoses involving multiple substances in the United States typically occur among people aged 25–54. However, a new study led by Boston University School of Public Health (BUSPH) and Mass General Brigham for Children indicates that polysubstance-involved opioid overdoses are also prevalent among youth.

Published in the journal Pediatrics, the study examined trends in overdose mortality and found that among youth, opioid overdoses more commonly involved multiple substances than opioids alone, starting at age 21. Polysubstance-involved overdose deaths occurred among youth as young as 15 years old, and rose steadily with age. The findings also demonstrated that fentanyl and other synthetic opioids were involved in more than 93% of overdose deaths, while stimulants such as methamphetamine and cocaine were the primary contributors to polysubstance-involved deaths.

“These findings indicate that overdose fatalities among youth under 25 are unfortunately mirroring trends seen in the general adult population, indicating the youth overdose crisis has entered a fourth wave,” says study lead and corresponding author Connor Buchholz, Ph.D. student in health services and policy research at BUSPH.

This latest wave of the decades-long opioid epidemic centers on the combined use of stimulants and synthetic opioids, and follows previous waves driven by prescription opioids in the 1990s, heroin in 2010, and fentanyl and other synthetic opioids since 2013.

In 2023, 48.5 million people aged 12 or older had had a substance-use disorder in the previous year, and drug overdose deaths more than doubled among adolescents from 2018 to 2022. As drug overdose deaths in the U.S. remain alarmingly high despite a decline in 2024 from 2023, the new findings underscore the need for tailored treatment strategies among youth to address rising overdoses involving synthetic opioids combined with stimulants.

The study analyzed federal overdose mortality data for youth aged 15–24 from 2020 to 2023, comparing opioid overdoses involving multiple substances with opioid-only fatalities. Polysubstance use drove nearly half of the 23,000 youth opioid overdose deaths during this period. Stimulants were involved in 65% of polysubstance opioid overdose deaths and 33% of all opioid overdose fatalities.

Among the approximately 23,000 opioid overdose deaths that occurred in youth during this period, polysubstance-involved overdoses contributed to 25% of opioid overdose deaths among 15-year-olds, 40% among 18-year-olds, nearly 53% of these deaths among 21-year-olds, and 58% among 24-year-olds. Other than opioids, stimulants were the most common substance involved in overdose deaths, and were used in approximately 12% of opioid overdose deaths among 15-year-olds, 21% among 18-year-olds, 34% among 21-year-olds, and 41% among 24-year-olds.

Although the study did not directly analyze the specific factors that are driving age-related increases in polysubstance-involved overdose deaths, the researchers point to several likely factors: wider availability of illicit drugs, rising potency of drugs, and worsening mental health challenges.

“Despite a reduction in opioid prescriptions, youth remain at risk of unintentionally encountering counterfeit pills that resemble medications such as oxycodone, benzodiazepines, and other prescription drugs, which can be contaminated with fentanyl,” Buchholz says.

Rising rates of mental health conditions may also be driving youth to turn to substances as a way to cope with difficult emotions,” he adds.

“Rates of attention-deficit/hyperactivity disorder [ADHD] have increased in recent years, and symptoms of ADHD and other mental health conditions were likely exacerbated during the COVID-19 pandemic.”

The forthcoming funding cuts to Medicaid under the recently passed federal tax and spending bill may further complicate this crisis by reducing access to medications for opioid use disorder (OUD), including buprenorphine, methadone, and naltrexone.

“Medicaid is a primary source of coverage for youth with OUD, and many youth and their families rely on this lifesaving treatment, which has been proven to substantially reduce the risk of opioid overdose,” says study senior author Dr. Scott Hadland, chief of the Division of Adolescent and Young Adult Medicine at Mass General Brigham for Children/Harvard Medical School.

“Early intervention, particularly among youth, is critical to preventing overdoses, avoiding serious long-term health consequences, and reducing the risk of decades-long addiction.” The budget cuts will also reduce funding for programs that provide the overdose-reversal medication Narcan (naloxone) to first responders, which could jeopardize recent progress in combating the opioid crisis, he adds.

Despite these challenges, clinicians can continue to promote substance-use recovery by promoting nonstigmatizing and developmentally appropriate care, Buchholz says, citing treatment guidelines from U.S. medical organizations for youth with OUD and stimulant use disorders (StUD).

“To mitigate overdose risk, comprehensive education on overdose prevention, including the administration of Narcan, should be widely implemented for all clinicians treating youth with OUD,” Buchholz says. For youth with StUD, “recommended treatments include off-label medication use, contingency management, and behavioral therapies.”