This Week’s Focus: Nitazenes

Nitazene analogs—high-potency synthetic opioids—are increasingly implicated in overdose deaths across the United States. In 2023, metonitazene and isotonitazene were most frequently detected as reported by the CDC. Labs use novel approaches to discover these analogs in toxicology specimens and drug materials, but they can often be missed due to their low concentrations or novelty, which evades routine toxicological screening. When detected they are often found with fentanyl or benzodiazepines.

This week’s NDEWS Briefing features NDEWS original analyses from biospatial.io, and recent US and global findings on nitazene pharmacology, postmortem detection, and public health responses. New data from wastewater, casework, and forensic studies underscores the need for improved surveillance, analytical capacity, and clinical preparedness.

In this week’s report, NDEWS highlights observations from biospatial.io detailing EMS encounters for nitazene-related overdoses in the US from January 2023 to April 2025. The data shows that most counties were located in the southeastern region. Of the total 18,449 EMS encounters, 18,332 (99.4%) were in response to nonfatal overdoses, while 117 (0.6%) were reported as being in response to fatal overdoses involving nitazenes.

Complementing these data, the University of North Carolina at Chapel Hill's  (UNC) Street Drug Analysis Lab has detected nitazenes in 135 samples as of April 30, 2025. Analyzed samples were submitted from 14 states, including Georgia, Wisconsin, and South Carolina—aligning with the biospatial summary highlighted in this NDEWS Special Report. Protonitazene and metonitazene were the most frequently identified compounds by the UNC Street Drug Analysis Lab . All nitazene detections were in powder form; none were in counterfeit pills.

To view the entire Special Report from our Weekly Briefing, click here.
Click here to learn more about NDEWS Hotspot Alerts

New data from the CDC’s State Unintentional Drug Overdose Reporting System (SUDORS) reveal that 320 overdose deaths across 38 jurisdictions in 2023 involved nitazene analogs—potent synthetic opioids that often surpass fentanyl in strength. As shown in this national map, nitazene-involved deaths were most concentrated in Ohio, Pennsylvania, and Illinois, but occurred across a wide geographic range. The most commonly implicated compounds were metonitazene and isotonitazene. While international cases have made headlines, the US currently bears the highest documented burden of nitazene-related mortality, underscoring the urgent need for expanded drug surveillance, toxicology capacity, and harm reduction strategies.
Read the report here.

A recently published analysis by the United Nations Office on Drugs and Crime (UNODC) Early Warning Advisory highlights the global spread of nitazene-class synthetic opioids, with 26 different nitazenes identified across 30 countries by early 2025. Between 2019 and 2024, 292 toxicology cases involving nitazenes were reported to UNODC, the majority (82%) being fatal overdoses. Protonitazene, metonitazene, and isotonitazene were the most commonly detected nitazenes in toxicology cases. Six nitazenes have been placed under international control, and four additional nitazenes have been recommended for scheduling by the World Health Organization following their 2024 review.
Read the report here.

A recent April 2025 intelligence bulletin from Houston High Intensity Drug Trafficking Area (HIDTA) highlights increasing detections of nitazenes—particularly N-pyrrolidino protonitazene—in counterfeit M30, oxycodone, and alprazolam tablets across Southeast Texas. First identified in the region in late 2023, these synthetic opioids are reportedly linked to overdose clusters and sought by some users due to their extreme potency and ability to evade routine toxicology screens. The bulletin notes that forensic labs and public health agencies are expanding nitazene testing and surveillance in response.
Read the report here.

A recently published study in Environmental Science and Pollution Research by Keller et al. validated a highly sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method using solid-phase extraction (SPE) to detect nitazene analogs and xylazine in Australian wastewater. Among 180 samples collected from 60 sites, five nitazenes were detected at low frequencies (2–6%), while xylazine appeared in 26% of samples at concentrations up to 207 nanograms per liter (ng/L). The method’s ability to detect trace levels and distinguish nitazene isomers using LC–MS/MS and SPE offers an important early warning system for emerging synthetic opioids. This article in The Guardian highlighted the public health urgency, which linked these findings to rising overdose deaths across Australia.
Read the study here.

A recently published comment in The Lancet Public Health by Holland et al. discusses the emergence of nitazenes as a potential driver of a “second wave” in the UK’s drug-related death crisis. Nitazenes, synthetic opioids hundreds of times more potent than heroin, have been increasingly detected in substances sold as opioids and benzodiazepines. The UK National Crime Agency identified 54 deaths involving nitazenes over a six-month period, though the true scale is likely underestimated.
Read the comment here.

A recently published study in the Journal of Pharmaceutical and Biomedical Analysis by Wachełko et al. developed and validated a UHPLC-MS/MS method for detecting 26 benzimidazole opioids (nitazene analogs) in biological samples. Using PFP and C18 stationary phases and multiple reaction monitoring (MRM), the method achieved exceptionally low limits of quantification (10 pg/mL for most compounds) and successfully separated challenging isomeric pairs. The study also revealed fragmentation patterns for each analog, aiding rapid identification of novel nitazenes.
Read the study here.

A recently published study in Rapid Communications in Mass Spectrometry by Liu et al. characterized mass spectrometry fragmentation patterns of nitazene analogs to improve rapid structure identification. Using ultra high-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS) with electron-activated dissociation (EAD), the researchers analyzed 11 nitazene compounds and revealed key fragmentation pathways. They developed a flowchart-based method for predicting novel nitazene structures, which was successfully applied to identify three new analogs—butonitazene, N,N-dimethylamino etonitazene, and ethylene etonitazene—in seized herbal blends.
Read the study here.

A recently published review in Neuropharmacology by Vandeputte and Stove provides a detailed overview of nitazene synthetic opioids, highlighting their rapid emergence since 2019. The authors identify 22 distinct nitazene analogs now circulating globally, many of which are more potent than fentanyl at activating the μ-opioid receptor. The review discusses their chemical structures, structure-activity relationships, detection challenges, and increasing role in overdose deaths. It also stresses the urgent need for improved harm reduction, forensic detection, and regulatory strategies, especially as nitazenes infiltrate traditional heroin markets in the wake of global opioid supply disruptions.
Read the review here.

A recently published scoping review in Journal of Medical Toxicology by Berger et al. examined 19 cases of nitazene overdose involving metonitazene, isotonitazene, protonitazene, and etonitazene. Median naloxone doses ranged from 1 mg (protonitazene) to 6 mg (metonitazene), with 59% of cases requiring multiple doses. Mean hospital stays varied widely, from 20 hours (protonitazene) to 360 hours (metonitazene). The review highlights limited testing capacity, frequent co-ingestion with other substances, and the urgent need for better clinical protocols to manage nitazene-related overdoses.
Read the review here.

A recently published study in Addiction by Bade et al. conducted the largest international wastewater surveillance effort to date targeting nitazenes, a class of highly potent synthetic opioids. Over two New Year periods (2022–2024), 683 samples were collected across 68 sites in 22 countries, revealing the presence of protonitazene and etonitazepyne in US and Australian wastewater. Notably, a spike in protonitazene in Australia on December 30, 2023, suggested possible direct disposal, later followed by reports of local overdoses involving the compound. 
Read the study here.

A recent media article in The Conversation highlights the growing global threat of nitazenes and synthetic opioids, noting their increasing prevalence in the UK and Europe. Since 2021, nitazenes—such as isotonitazene—have been linked to hundreds of deaths in the UK, often found fortifying low-purity heroin or counterfeit pills. Nitazenes, with potencies comparable to or greater than fentanyl, are cheaply synthesized, widely advertised online, and smuggled into Europe primarily from China. Despite current relatively low levels of nitazene use compared to heroin, experts warn that market instability, such as reduced Afghan heroin supply, could accelerate their adoption, posing major challenges for public health and law enforcement.
Read the article here.

You are invited to attend the NDEWS Summit at the College on Problems of Drug Dependence (CPDD) 87th Annual Scientific Meeting on Saturday, June 14th (06/14/2025) from 4:00 pm - 6:00 pm CT in Bayside Ballroom AB, 4th floor. The Summit will be open to all CPDD meeting attendees. 

We hope to see you there!

NDEWS Posters and Presentations at CPDD

In June, the NDEWS team will be traveling to attend the 87th College on Problems of Drug Dependence (CPDD) Annual Meeting in New Orleans, Louisiana. Along with posters, the NDEWS team will be presenting a late-breaking abstract, an oral presentation and two invited symposia. We invite you to join us for these presentations. Please find the presentation information below:

Sunday, June 15
3:30 pm - 4:45 pm CT Late-Breaking Abstract
Anesthetics (“-Caines”) Adulterate the Illicit Fentanyl Supply: A National Drug Early Warning System (NDEWS) Alert
Joseph Palamar, Joshua DeBord, Alex Krotulski, Bruce Goldberger

5:00 pm - 6:30 pm CT Poster Session 1 (Napoleon Ballroom CD, 3rd Floor)
Trends in Nonfatal Fentanyl Poisonings Involving Stimulants in the United States, 2015–2023
Nicole Fitzgerald, Joshua Black, Linda Cottler, Silvia Martins, Joseph Palamar

Monday, June 16
10:45 am - 12:15 pm CT Invited Symposium
Found in Translation: Coordinated Preclinical, Human Laboratory and Epidemiological Approaches to Understanding Polydrug Use
William Stoops, Lori Knackstedt, Linda Cottler, Christa Corley

3:30 pm - 4:30 pm CT Oral Session: Sex Matters: Translational Evaluations of Sex-Specific Factors in Substance Use
Sex Differences in Problematic Substance Use, Mental Health, and Social Determinants of Health among Middle-Aged and Older Adults in the All of Us Research Program
Vijaya Seegulam, Bia Whipp, Liva LaMontagne, Linda Cottler

5:45 pm - 7:15 pm Poster Session 2 (Napoleon Ballroom CD, 3rd Floor)
Natural Language Processing Analysis of 7-Hydroxymitragynine Reddit Discussion
Daniel Van Zant, Kirsten Smith, Oliver Grundmann, Catherine Striley, Elan Barenholtz, Christopher McCurdy, Linda Cottler

Tuesday, June 17
3:45 pm- 4:45 pm CT Oral Presentation at Mini Symposium: Prevalence and Characteristics of Recreational Ketamine Use among Nightclub Attendees and College Students in the New York Tristate Area.
The Current Landscape of Medical and Recreational Ketamine Use
Shahar Almog, Meredith Berry, Joseph Palamar 

5:30 pm - 7:00 pm CT Poster Session 3 (Napoleon Ballroom CD, 3rd Floor)
Reported Use of Recreational and Medical Cannabis, Delta-8, and Delta-10: Findings from NDEWS Sentinel Sites and Hotspots (2022–2023)
Tamara Millay, Vijaya Seegulam, Monica Bhargavi Kodali, Linda Cottler

Wednesday, June 18
2:00 pm - 3:30 pm CT Poster Session 4 (Napoleon Ballroom CD, 3rd Floor)
Alcohol Polysubstance Use among past 30-Day Opioid Users in Northern Florida: A Model for Back Translational Research
Christian Conger, Linda Cottler

📅 Date: Thursday, May 8, 2025

🕑 Time: 2:30 pm ET

📍 Location: Online

Learn more here.

📅 Dates: May 29 - May 30, 2025

📍Location: UF Academic and Research Center at Lake Nona, Orlando, FL

Learn more here.

📅 Dates: June 2 - 4, 2025

📍 Location: University of Puget Sound, Tacoma, WA

Learn more here.

📅 Date: Thursday, June 12, 2025

🕑 Time: 12:00 pm ET

📍 Location: Online

Learn more here.

📅 Date: Friday, June 20, 2025

📍 Location: New Orleans

Learn more here.

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If you miss or want to learn more about NDEWS Original Content, you can find our archived content on the NDEWS website:

     • NDEWS Hotspot Alerts using substance-related EMS data
     • NDEWS Rapid Street Reporting (RSR) survey data reports
     • NDEWS Web Monitoring Team Reddit Alerts
     • NDEWS Sentinel Site Reports
     • Previous issues of the NDEWS Weekly Briefings

The Weekly Briefing is a newsletter published each week by the National Drug Early Warning System (NDEWS) Coordinating Center, which is funded by the National Institute on Drug Abuse (U01DA051126) to the University of Florida (MPI: Cottler (contact), Co-Is: Goldberger, Nixon, Striley), New York University (MPI: Palamar), and Florida Atlantic University (Co-I: Barenholtz). Any item may be reproduced provided the source is acknowledged.