A new class of synthetic drugs is quietly embedding itself into the United States illicit drug supply, and the numbers tell a deeply troubling story. Nitazene synthetic opioids, a group of compounds with no approved medical use, surged from just 43 recorded detections in 2019 to 1,905 in 2024, according to data from the US Drug Enforcement Administration’s National Forensic Laboratory Information System (NFLIS). That is a more than 44-fold increase in five years.

What Are Nitazene Synthetic Opioids?

Pharmaceutical researchers first synthesised nitazene synthetic opioids in the 1950s while exploring alternatives to morphine. Companies shelved them almost immediately because of extreme potency and poor safety profiles. Some analogues, such as isotonitazene, carry in vitro potencies up to 500 times greater than morphine.

For decades, nitazenes remained little more than a footnote in pharmacology. Around 2019, they began appearing in the US illicit drug supply in earnest.

Overseas industrial laboratories typically manufacture these substances. Suppliers, often based in China, sell them through online marketplaces. Distributors then press them into counterfeit tablets or mix them into heroin and fentanyl powders. Users rarely know what they are taking.

The Rise and Plateau of the Synthetic Opioid Crisis

Research published in the journal Addiction in early 2026 offers the most comprehensive national picture of nitazene detections to date. Researchers from Virginia Commonwealth University, Columbia University, NYU and the Center for Forensic Science Research and Education (CFSRE) drew on two major forensic data sources across all 50 US states and the District of Columbia between 2019 and 2024.

Their findings paint a picture of a crisis that erupted rapidly and has since settled into a persistent presence.

NFLIS nitazene reports grew more than sevenfold per year between 2019 and 2021. Growth slowed after 2021, but detections did not fall. Researchers describe this plateau as evidence that the synthetic opioid crisis now includes nitazenes as a stable, entrenched component rather than a passing trend.

The CFSRE’s NPS Discovery programme, which tracks novel psychoactive substances through biospecimen testing, identified 361 unique nitazene-positive biospecimens over the same period. That figure climbed from 11 in 2019 to 113 in 2024, growing at roughly 45% per year with no sign of levelling off.

The Analogue Shift: A Moving Target

One of the most striking patterns in the data is how quickly the dominant nitazene analogue has changed.

In 2019, isotonitazene accounted for nearly 98% of all nitazene detections. By 2024, its share had fallen to just 2.3%. That sharp decline closely tracked its scheduling under the Controlled Substances Act, with temporary placement in 2020 and a permanent Schedule I listing in 2021.

Rather than reducing the overall scale of the synthetic opioid crisis, scheduling appeared to accelerate a pivot toward new compounds. Metonitazene rose quickly to dominate detections from 2021 onward, accounting for nearly 46% of all NFLIS nitazene reports across the study period. Regulators temporarily scheduled it in 2022 and permanently in 2023, and its share of detections began to dip in 2024.

Protonitazene has since emerged as a growing concern. Regulators temporarily scheduled it in 2022 and permanently in 2024, yet detections kept climbing. By 2024, protonitazene accounted for 30% of all NFLIS nitazene reports, up from just under 2% in 2021. Unlike isotonitazene and metonitazene, protonitazene shows little sign of responding to regulatory pressure so far.

Across the full study period, the number of distinct nitazene analogues in NFLIS grew from just two in 2019 to 18 in 2024, with 21 individual compounds detected in total.

Nitazene Synthetic Opioids: A Crisis Concentrated in Specific States

The geography of detections is far from uniform. More than half of all NFLIS reports across the six-year study period came from just three states: Ohio (37.6%), Florida (10.6%) and Tennessee (6.7%).

Ohio has been at the epicentre. Isotonitazene peaked there in 2021 with 264 reports. Metonitazene also peaked in Ohio in 2021, reaching 368 reports. Protonitazene then climbed to 263 reports in Ohio by 2024.

Florida recorded high concentrations of protonitazene and N-pyrrolidino etonitazene. Researchers point to maritime entry points as a possible factor behind those patterns. Tennessee was among the first states to document clusters of nitazene-related fatalities.

The Midwest consistently led nationally, accounting for 53.1% of all nitazene reports, followed by the South at 33.8% and the Northeast at 11.0%. The Northeast saw a sharp acceleration from 2022 onward, with reports climbing from near zero in 2019 to 362 by 2024. The Western US remained comparatively less affected at just 2.1% of national detections, though its numbers are rising steadily.

Five states recorded no nitazene reports at all across the study period: New Mexico, Hawaii, Montana, Oklahoma and South Dakota.

Almost Never Found Alone

Perhaps the most urgent finding for clinicians and harm reduction workers concerns the near-universal pattern of polysubstance involvement.

Of the 361 nitazene-positive biospecimens identified through NPS Discovery, 98.3% contained at least one other substance. Each biospecimen tested positive for 7.6 additional compounds on average. Nearly a third contained 10 or more.

Fentanyl topped the list of co-detected substances, appearing in 54.6% of all nitazene-positive biospecimens. For metonitazene-positive samples, that figure rose to 59.3%. Fentanyl-related compounds such as 4-ANPP and norfentanyl also appeared frequently.

Methamphetamine showed up alongside nitazenes in 31.6% of biospecimens. Cocaine appeared in 29.9%. The veterinary sedative xylazine, already a growing concern in the fentanyl supply, turned up in 23.8% of nitazene-positive cases and in nearly 29% of those specifically involving metonitazene.

This level of polysubstance involvement complicates both clinical treatment and overdose response. Naloxone, the standard opioid reversal agent, may require multiple doses when facing a nitazene exposure. Add stimulants, sedatives or other opioids into the mix, and the result is an unpredictable and potentially fatal combination.

How the Synthetic Opioid Crisis Is Spreading Globally

The synthetic opioid crisis extends well beyond US borders. A 2025 report from the European Union Drugs Agency (EUDA) identified 22 distinct nitazene analogues across 21 European countries between 2019 and 2024. The Baltic states have been especially hard hit. In Estonia, nitazenes contributed to 42% of overdose deaths in 2023. England recorded 179 nitazene-involved overdose deaths between 2023 and 2024. Scotland saw 76 such deaths in 2024 alone, more than three times the 2023 figure.

Norwegian data showed that over 90% of nitazene-related deaths involved other novel psychoactive substances, closely mirroring what US researchers found.

The authors of the Addiction study argue that this global spread underlines the need for coordinated international surveillance. Closer collaboration between US agencies and the EU Early Warning System, along with timely cross-border data sharing, would help detect new compounds before they reach critical mass.

What Needs to Happen Now

Researchers are clear: tackling nitazene synthetic opioids requires more than scheduling individual compounds. They call for expanded toxicology testing across jurisdictions, standardised laboratory protocols, and investment in drug checking programmes capable of identifying a broad and rapidly evolving range of substances.

Nitazene test strips show promise as a point-of-care tool. Laboratory evaluations found that current strips detect between 24 and 28 of roughly 33 to 36 nitazene analogues. Compounds lacking the 5-nitro group, known as desnitazenes, remain undetectable by current strips. False positives in the presence of caffeine, a common adulterant, also remain a concern at concentrations above 300 micrograms per millilitre.

Wastewater surveillance offers another population-level option. The EU already uses this approach to monitor nitazene trends at scale, and the first detection of protonitazene in wastewater has already been recorded. Interest in applying the same methods across the US is growing.

CDC SUDORS data make the stakes plain: fatalities linked to nitazene synthetic opioids jumped from 27 in 2020 to 320 in 2023, a more than tenfold increase in just three years. New analogues keep appearing, polysubstance combinations keep shifting, and current testing tools remain incomplete.

Knowing what is in the drug supply, and acting on that knowledge with urgency, has never mattered more.

Source: dbrecoveryresources