Historic decline in U.S. overdose deaths threatened by changing street drug supply

A forensic chemist with the Drug Enforcement Administration holds vials of fentanyl pills at a DEA research laboratory in this file photo. Fentanyl deaths are plunging in the U.S, but the recovery is threatened by a new "synthetic soup" of toxic street drugs. Mark Schiefelbein/AP/AP

Mark Schiefelbein/AP/AP

Earlier this year, Naida Rutherford, the coroner in Richland County, South Carolina, was helping investigate what appeared to be a mysterious overdose. The case had many of the hallmarks of a typical fentanyl death.

"Every sort of physical manifestation, like the foam coming from the mouth and nose, as if they had an overdose," Rutherford said. "Their blood tested negative for any substance, which was very odd."

Her team was stumped, so Rutherford expanded the testing, looking for new compounds. "That's where we found the cychlorphine," she told NPR, referring to one of the incredibly potent synthetic opioids spreading fast in the U.S. street drug supply.

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"This is the first time we've seen it in South Carolina, which is very scary because none of us knew to test for it."

Experts say the U.S. addiction crisis is evolving fast, in ways that appear both hopeful and incredibly dangerous. The peril comes from a street drug supply that chemists now describe as a "synthetic soup."

Where once most drug users mostly consumed plant-based substances such as cocaine and heroin, drug gangs and cartels have shifted to producing and selling synthetic substances made from industrial chemicals.

Fentanyl and methamphetamines have been around for years. Now, illicit chemists are adulterating batches of street drugs with a fast-changing and often baffling mix of compounds, ranging from Novocaine to a stabilizer used in plastics manufacturing called BTPMS.

"Why those in particular are being put into the drug supply is a bit of a medical mystery at this point," said Nabarun Dasgupta, a researcher who studies street drugs and overdose patterns at the University of North Carolina.

"We're encountering something we've never seen before"

"Once a month or every other month, we're encountering something that we've never seen before, and we don't have indications of it being seen in the United States before," said Ed Sisco, a research chemist with a federal agency that tracks and tests street drugs called the National Institute of Standards and Technology.

The list of new chemical substances is dizzying. There are dangerously powerful sedatives like medetomidine, which can damage the human heart, and xylazine, sometimes known as tranq, which often causes devastating flesh lesions. Public health officials say new types of synthetic opioids, including cychlorphine and nitazenes, are often more potent than fentanyl.

According to Sisco, street drug users now have no way of knowing what they're putting in their bodies. "Substances that are in the supply are constantly changing and the other thing we see is the amount [and potency] of the substances is constantly changing," he said.

That variability makes it impossible for even experienced street drug users to protect themselves from toxic batches and potentially lethal doses. These unpredictable drug "cocktails" are also often resistant to standard medical treatments, like Narcan and naloxone, used to reverse opioid overdoses.

Medetomidine, in particular, is far more complicated to treat after an overdose or when a person goes into withdrawal from the drug, often requiring extensive and costly hospital care.

"The problem with medetomidine is that the withdrawal from it is life-threatening if you quit cold-turkey," said Dasgupta. "That is not the case with fentanyl or xylazine."

This month, the Centers for Disease Control and Prevention issued a health alert warning of the spread of medetomidine. State attorneys general in South Carolina and other states have warned of the spread of cychlorphine.

Drug deaths still dropping

The good news, researchers say, is that so far the spread of these industrial, toxic chemicals in the street drug supply hasn't derailed what amounts to a historic, sustained drop in the number of people dying from fatal overdoses.

As of October 2025, the most recent month where preliminary data is available from CDC, roughly 71,542 people had died in the U.S. over a 12-month period.

That's down dramatically from the 12-month peak of nearly 113,000 drug deaths recorded in August 2023.

"This is unprecedented and historic, for the longest consecutive months of decline," said Lori Ann Post, a researcher at Northwestern University whose new paper in the American Journal of Public Health tracks the steady improvement. "That is awesome."

Most researchers credit a mix of factors for the recovery, from less potent illicit fentanyl on the streets to better health and addiction care.

According to Post, deaths from opioids — including pain pills, heroin, fentanyl and other synthetic opioids — declined so rapidly in the U.S. that for the first time in decades overdoses from stimulants like cocaine and methamphetamines now kill more people than opioids.

"Opioids went way down. We have better interventions to treat opioid use disorder, we have reversal agents like Narcan [also known as naloxone] to undo an overdose," she said.

"This is what we've been waiting for, to turn the tide," said Dasgupta, at the University of North Carolina. He pointed to the stunning drop in mortality for young people across the U.S., citing a particularly hopeful development in the state of Maine.

"It's remarkable that no one in Maine under age 25 has died [from a drug overdose] in nearly 12 months. Zero is a meaningful number," Dasgupta said.

But every expert interviewed for this story said the situation in U.S. communities remains perilous as chemicals in the street drug supply become more potent and unpredictable.

Post and Dasgupta pointed to a crisis in Baltimore, Md., last summer when dozens of people were rushed to the hospital for overdoses after being exposed to a new variety of illicit benzodiazepines. Fortunately, in that case, everyone survived, but the potential for injury or death from drug poisoning remains high.

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One mystery that street drug researchers are trying to unravel is why drug cartels and dealers would create an illegal marketplace so dangerous for customers, often selling batches of street drugs so heavily laced with chemicals that they make people sick rather than producing the euphoric high that buyers crave.

According to Dasgupta, gangs that are mixing synthetic street drugs are increasingly "turning to [chemicals] that aren't desirable."

He believes this spread of heavily adulterated fentanyl, and other drugs, could actually be contributing to the drop in overdose deaths as more people opt out of risky drug use.

"People who have been using for a long time are saying, that's enough, that's not what I signed up for," Dasgupta said.