The United States may be entering a “fifth wave” of its overdose crisis, with stimulants like methamphetamine and cocaine increasingly replacing opioids as the primary driver of overdose deaths. Data from 2016 to 2025 shows a dramatic shift in drug use patterns among people with substance use disorder.
The Stimulant Surge
A report by Millennium Health, based on analysis of 1.69 million urine drug samples from 530,000 adults across all 50 states, found that stimulants have surpassed opioids as the leading cause of overdose death. From 2016 to 2025, the co-involvement of stimulants in fentanyl overdose deaths increased 164 percent. More significantly, the detection of methamphetamine and cocaine alone rose 4.5 percent and 13.5 percent respectively from 2024 to 2025. About 85 percent of those who tested positive for fentanyl also tested positive for an illicit stimulant—the highest proportion ever recorded by Millennium.
Regional differences in stimulant use are significant. Methamphetamine use is highest in the West at around 15 percent in both years, while the South recorded the highest use of cocaine alone, increasing from 7.2 percent of samples to 9.2 percent nationally.
Debate Over Wave Status
Experts disagree on whether the nation has entered a distinct fifth wave. Lori Ann Post, who tracks overdose data through Northwestern University’s Opioid Pulse dashboard, calls it “totally new” and “historic” that stimulants surpassed opioids as the underlying cause of death on U.S. death certificates in June 2025. Brian Hurley, immediate past president of the American Society of Addiction Medicine, contends the nation remains in the fourth wave but acknowledges stimulants may eventually overtake opioids nationally.
Treatment Gap
A critical challenge is the absence of effective treatment options. While fentanyl harm reduction has benefited from increased naloxone availability and medications for opioid use disorder, no approved medications exist for stimulant dependence. Contingency management, in which patients are rewarded for positive behaviors, is recognized as the most effective treatment for stimulant use disorder but remains underused. CDC data from the first six months of 2025 showed stimulants alone accounted for 26.2 percent of overdose deaths, with 14 percent from methamphetamine alone and 10 percent from cocaine alone.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.medscape.com/viewarticle/us-entering-fifth-wave-overdose-crisis-2026a10007my