Fentanyl-related overdose deaths have declined sharply in the United States, but rising use of illicit stimulants is creating new risks and clinical challenges, according to Millennium Health’s latest Signals Report.
The report, released in February 2026, highlights what researchers describe as a rapidly evolving drug landscape. While fentanyl detection and fentanyl-involved deaths have decreased in recent years, the use of methamphetamine and cocaine continues to rise across the country, often alongside opioids.
One of the report’s most notable findings: In 2025, 85% of individuals who tested positive for fentanyl also tested positive for at least one illicit stimulant, the highest proportion recorded in Millennium Health’s datasets. The data indicate fentanyl is now rarely detected in isolation among people with substance use disorders.
The increases were observed nationwide, with significant regional variation. Fentanyl-methamphetamine co-use rose 40.7% in the South between 2024 and 2025, while fentanyl-cocaine co-use increased 19.3% in the Northeast.
Researchers also found that, for the first time, every state analyzed showed methamphetamine or cocaine detected more frequently than heroin or prescription opioids among people using fentanyl. The shift reflects changing patterns of polysubstance use that have become a defining feature of the overdose crisis.
The findings arrive amid sustained national declines in overdose deaths, driven largely by reductions in fentanyl-related fatalities. However, the report cautions that rising stimulant use presents a distinct and growing challenge for clinicians and public health systems.
Unlike opioid use disorder, stimulant use disorder has no Food and Drug Administration-approved medications. Treatment typically relies on behavioral interventions, including contingency management, which researchers consider effective but difficult to implement broadly due to cost and reimbursement barriers.
The report also points to continued volatility in fentanyl detection. Urine drug testing data showed declines beginning in 2023, followed by a rebound in late 2024 and early 2025, a pattern Millennium Health said mirrors provisional overdose mortality data. A temporary increase in heroin and other opioid detections during 2024 may signal disruptions in fentanyl supply, the researchers noted.
Millennium Health’s analysis is based on more than 1.69 million de-identified urine drug test specimens collected from over 530,000 patients between 2016 and late 2025. The laboratory said its testing data can provide earlier indications of emerging drug trends than mortality statistics, which often lag due to reporting delays.
While fentanyl remains the leading driver of overdose deaths, the report emphasizes that stimulants are playing an increasingly prominent role in both fatal and nonfatal drug-related harms, including psychiatric complications and long-term health consequences.
The findings, researchers said, underscore the need for continued monitoring and adaptation as drug use patterns shift.
“The drug use landscape remains highly dynamic,” the report concludes, warning that increases in stimulant use — with and without fentanyl — could place additional strain on treatment systems and harm-reduction efforts.
