As efforts to fight the fentanyl trade ramp up, new synthetic opioids that are less detectable and sometimes stronger than the notorious drug are cropping up with greater frequency in the American market.
Multiple “analogues,” or variations, of opioids known as nitazenes have now been detected across more than a dozen states. Some are on par in potency with fentanyl, which has taken the lives of hundreds of thousands of drug users in just the last five years, compounding the already dire, decades-long opioid crisis in the country. Others, which are less prevalent but have been detected in the U.S., are exponentially more potent.
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And nitazenes’ presence in the market—as well as their involvement in overdose deaths—is likely being underreported, because the technology needed to identify them isn’t widely used in autopsies, posing unique problems for their detection.
Their emergence is being seen by scientists who track the spread of opioids around the country as a harbinger of a much different, more variable landscape of drugs about which comparatively little is known.
“We’re at this really unique inflection point where a lot of the fentanyl supply is contracting,” Dr. Nabarun Dasgupta, a scientist at the University of North Carolina’s Gillings School of Global Public Health who has been tracking nitazenes and other novel drugs within the U.S., tells TIME.
In the coming months and years, Dasgupta suggests, other drugs—potentially including nitazene analogues, as well as certain sedatives his lab has also detected in the drug supply—may become more prominent in the market and fill gaps fentanyl is leaving.
The sheer volume of fentanyl circulating into and within the country means a major shift in the opioid supply is not immediately imminent, according to experts.
But cracking down on one drug has led to the rise of another before, including in the case of fentanyl itself. And it’s possible the apparent increase in nitazenes across the country happening at the same time fentanyl’s presence is waning marks the beginning of a similar trend—though it may take years to establish, if it ever does.
“Fentanyl largely replaced heroin,” says Joseph J. Palamar, a professor at New York University who specializes in drug use epidemiology. “And I wonder, could nitazines replace fentanyl?”
What we see, and what we don’t
Dr. Dasgupta’s lab analyzes drug samples from over 40 states provided by roughly 200 public health agencies, clinics, hospitals, and health departments to provide up-to-date metrics on what drugs are circulating in American markets.
He has detected nitazenes in 15 states so far. Protonitazene and metonitazene, analogues of the drug that are similar in strength to fentanyl, are the most common on the East Coast. But data from Tennessee, which Dasgupta describes as a known “bellwether for synthetic opioids,” has shown the greatest concentration of the drugs in the U.S.
Alex Krotulski has done work similar to Dasgupta’s as the program manager for NPS Discovery, the Center for Forensic Science Research and Education’s drug early warning system, which monitors thousands of drug samples from around the country to rapidly identify emerging trends. The system has seen an increasing number of deaths from nitazenes in recent years.
Although nitazene-related deaths in Europe have garnered more attention, Krotulski says his research has yielded data indicating a far greater concentration of such deaths in North America.
“In general, the United States and Canada really bear the majority of nitazene consumption around the world,” he says. “Anyone who has intimate knowledge of the nitazene supply would know, or should know, that nitazenes in the U.S. and Canada are far above in terms of prevalence anywhere else.”
Krotulski notes that the U.S. lacks a “uniform way of tracking drugs,” and that the absence of this infrastructure suggests the country’s numbers are deflated.
That also makes it extremely difficult to predict how the drug supply is going to change, even as data is showing an influx of nitazenes analogues and other drugs.
The Centers for Disease Control and Prevention (CDC) categorizes synthetic opioid-related deaths without specifying if an overdose is attributed to nitazenes or a combination of both nitazenes and another drug, such as fentanyl. Meanwhile, the CDC’s State Unintentional Drug Overdose Reporting System (SUDORS) does not provide real-time data or differentiate lesser-known and widespread substances like nitazenes, which makes the intentional tracking of less common, yet emerging, drugs all the more important.
President Donald Trump’s budget request for Fiscal Year 2026 sought to eliminate “duplicative, DEI, or simply unnecessary programs” within the CDC, among which it listed the National Center for Injury Prevention and Control (NCIPC), a branch of the health agency that tracks opioid use and subsequently implements safety nets and new surveillance methods. SUDORS works out of the NCIPC, and Dasgupta warns that the center’s elimination would likely stymie the system’s ability to adapt to and detect novel drugs in the market. Trump’s budget request would slash the overall budget of the CDC by $3.6 billion. It’s not yet clear to what extent the requested cuts will be made, however: Congress is currently in the process of weighing government funding measures ahead of a Sept. 30 deadline.
In any case, Krotulski says, “I don’t think there’s ever going to be an accurate picture of what drug emergence looks like in the United States. We have a very underrepresented picture of what’s going on.”
‘A period of hyper-change’
Dr. Dasgupta attributes the emergence of the new drugs being detected in the market, in part, to enforcement pressure from the government.
The U.S. has been fighting for years across both Democratic and Republican Administrations to stop the spread of fentanyl and the devastation the drug has wrought across the country.
In his second term, Trump has redoubled his efforts to crack down on fentanyl trafficking by targeting cartels and seeking to ramp up fentanyl seizures and constrict the flow of people and products across the U.S.’s southern border.
In July, Trump signed the HALT Fentanyl Act into law, which classifies fentanyl as a Schedule I drug under the Controlled Substances Act and increases the punishment for traffickers.
“Today, we strike a righteous blow to the drug dealers, narcotic traffickers and criminal cartels that we’ve all been hearing so much about for so many years,” Trump said just before signing the bill in July. “We take a historic step toward justice for every family touched by the fentanyl scourge.”
This kind of effort to combat one drug ultimately leading another to emerge would not be without precedent. Dasgupta cited the “Iron Law of Prohibition,” which holds that drug markets begin to favor new products that are easier to trade, and potentially more potent, when law enforcement on a more common product intensifies. This dynamic was seen roughly ten years ago when heroin was largely replaced by fentanyl, which now dominates its predecessor in the U.S. market, Dasgupta explains.
That transition process happens gradually, however, and the U.S.’s detection infrastructure—as well as the ways nitazenes are moving within the country’s drug market—make it difficult to document.
“There is no one consistent supply chain across all 50 states,” says Sheila Vakharia, a national expert on harm reduction and policy. She explained how regional and urban supply chains interact within their own bubbles across the country, evolving at different rates and slowly introducing new substances like nitazenes into the market.
“What we see when these new drugs take hold, is that they start off in one market, one region, and they start to saturate that geographic area, starting usually with a city, but then kind of spreading to the rural areas surrounding it,” Vakharia explains to TIME.
Palamar, the NYU drug use epidemiology professor, suggests it’s possible that now “nitazenes, oftentimes more potent than fentanyl, could come creeping into the supply and replace fentanyl.”
Palamar is also the Deputy Director of the NIDA-funded National Drug Early Warning System (NDEWS), which provides timely data on emerging substance use trends. He says NDEWS’s research has found that fentanyl is harder to find, more expensive and weaker, according to recent data.
But he says he doesn’t know the extent to which nitazenes are coming in to fill the gap, because “oftentimes the nitazenes are co-present with fentanyl in the supply,” meaning they might be mixed in with other drugs without the knowledge of the user.
Krotulski, the NPS program manager, notes that while the mixing of nitazenes with other drugs has been documented in low numbers, the fentanyl and nitazene supplies are by no means directly linked.
Fentanyl mostly comes to the U.S. through Mexico, while nitazenes are primarily produced in China. They “merge and overlap at times,” he says, but the two don’t directly influence each other because their supply chains for the most part operate on their own.
“It is possible that if fentanyl decreases that nitazenes could increase, but that doesn’t have to necessarily be the case,” he tells TIME.
By all accounts, the increasing—and likely underrepresented—presence of nitazenes in the U.S. does not come close to rivaling the fentanyl trade at this point.
But their emergence is indicative of a market that is undergoing a period of unpredictable shifts and diversification and that is, once again, being changed into something new and unknown.
“Fundamentally, an unregulated drug supply is going to always be changing,” Dasgupta says. “And we’re just at kind of a period of hyper-change that we’ve never seen before.”