Author: Alicia Ault
The use of stimulants , typically in conjunction with opioids, has risen steadily since at least 2015, but several new reports indicate a potential shift away from opioids toward stimulant use alone.
From 2016-2025, the co-involvement of stimulants in fentanyl overdose deaths increased 164%, according to a new report by Millennium Health, a San Diego-based specialty lab that conducts urine drug test screens.
This continues a trend previously reported by Medscape Medical News, which documented a “fourth wave” of the opioid epidemic that was marked by an increase in use of stimulants combined with opioids, most commonly fentanyl.
But the new report, based on more than 1 million samples taken from half a million adults from 2016 to 2025, showed a potentially even bigger transition toward stimulant use alone, primarily methamphetamine and cocaine.
Experts say the data, combined with similar reports, could signal a “fifth wave’ of the nation’s overdose crisis.
Continued Rise in Stimulant Use
The eight annual Signals Report from Millennium documents illicit drug trends based on analysis of 1.69 million urine drug samples from 530,000 adults with substance use disorder in all 50 US states.
While the data suggest a significant drop in fentanyl use in 2025, about 85% of those who tested positive for fentanyl also tested positive for an illicit stimulant — the highest proportion ever recorded by Millennium. Researchers also found a sharp rise in stimulant use not only in conjunction with fentanyl but also more strikingly in the absence of any opioid.
The detection of methamphetamine and cocaine alone in urine specimens rose by 4.5% and 13.5%, respectively from 2024 to 2025. The prevalence of methamphetamine use was nearly double that of cocaine use nationally.
But the type of stimulant used differed by region.
Methamphetamine use was highest in the West, at around 15% in both years. And the South recorded the highest use of cocaine-alone.
Cocaine-positive specimens increased 13.5% nationally, with the biggest growth in the South — from 7.2% of samples to 9.2%. Just under 4% of samples in the West were positive for cocaine only compared with 7.5% in the Northeast and 6.6% in the Midwest.
Stimulant use “remains a significant — and still growing — concern with major public health implications and clinicians may not be fully equipped with the tools they need,” the report authors wrote.
A ‘Fifth Wave?’
Lori Ann Post, PhD, who tracks drug overdose data through The Opioid Pulse dashboard at Northwestern University Feinberg School of Medicine in Chicago, has also documented the shift toward stimulant use.
Stimulants surpassed opioids as the underlying cause of death on US death certificates in June 2025, said Post, director of the Buehler Center for Health Policy and Economics.
“That’s totally new,” Post told Medscape Medical News. “That is historic.”
Post believes the nation is now entering a “fifth wave” of the overdose crisis, one that is “dominated by stimulants, not by polysubstance” use, she said.
But Brian Hurley, MD, immediate past president of the American Society of Addiction Medicine (ASAM), disagrees.
“We’re still in the fourth wave,” he told Medscape Medical News. But if the rate of opioid overdose deaths continues a downward trajectory, “we might actually see stimulants overtake opioids,” said Hurley.
However, that is not yet true nationally yet or in Los Angeles, where he practices, he said. In that city, fentanyl-involved overdoses have declined by one third, but overdoses that also include stimulants (mostly methamphetamine) have only dropped by about 20%, he said.
Lack of Treatment an Issue
Some of the fentanyl harm reduction has come from increased availability of naloxone for acute overdoses and better access to medications to treat opioid use disorder, he said.
“We’re not seeing that same deployment of effective treatment for stimulant use disorder,” Hurley noted.
In 2023, ASAM and the American Academy of Addiction Psychiatry (AAAP) jointly issued a Clinical Practice Guideline on the management of stimulant use disorder.
One of those strategies is contingency management, in which patients are rewarded for positive behaviors.
But there are no approved medications for stimulant dependence, although the ASAM-AAAP guideline recommended consideration of off-label use of some therapies, such as bupropion and naltrexone.
Stimulant users tend to die from cumulative effects of the drugs, such as pulmonary hypertension, strokes and heart attacks, said Hurley.
CDC Data Confirms but Is Lagging
The CDC has also taken note of the increasing percentage of deaths involving stimulants combined with other substances or stimulants alone.
In an August 2025 report in the Morbidity and Mortality Weekly, agency researchers noted that from January 2021 to June 2024, 59% of deaths overall involved stimulants.
During those 3 years, 15.9% (50,000) deaths involved stimulants and no opioids. The individuals who died from stimulants alone were older (with two thirds older than age 45) and more frequently had a history of cardiovascular disease.
Contingency management “is the most effective treatment for stimulant use disorder but remains underused,” the CDC analysts wrote.
More recent CDC data, from the first 6 months of 2025, showed a continuing increase in stimulant-alone deaths. From January to June last year, 26.2% of overdose deaths involved stimulants alone, according to preliminary data posted to the State Unintentional Drug Overdose Reporting System dashboard. Some 14% were from methamphetamine alone and 10% from cocaine alone.
In 2025, the CDC reported 8951 deaths from methamphetamine and 7519 from cocaine. Combined, that is more than the 15,914 reported deaths from opioids.
Post said her Opioid Pulse dashboard shows that stimulants will continue to overtake opioids in terms of overdose deaths.
The dashboard, which uses metrics to try to send out early warnings, aims to address the 4- to 4.5-month lag in CDC reporting.
“By the time deaths appear in official data, the conditions driving them may already have shifted,” she and her co-researchers wrote in their latest brief.