This Week’s Focus: NDEWS shows downward trend in Nitazene non-fatal overdoses with a growing negative sentiment

In this week’s Briefing, our focus turns to nitazenes, a synthetic opioid that has been detected in the illicit drug market. Nitazenes are known for their high-potency, which in some cases can be greater than that of fentanyl.

Recent findings from our latest NDEWS Special Report and Web Monitoring Report show a decline in non-fatal nitazene-related overdoses along with a growing negative sentiment for nitazenes among Reddit commentors online.

Labs use novel approaches to discover these nitazene 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. We will be monitoring this situation, and we welcome your input.

Out of 1,996 EMS encounters for nonfatal nitazene-related overdoses from January 1, 2024 to October 31, 2025, the data shows that nearly all counties with nonfatal nitazene-related overdoses were located in the Southeast region of the US.

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Why are we reporting on this?
Although discussion of nitazenes has decreased, it still continues as one of the most highly discussed class of substances across monitored substance use subreddits.

What are Nitazenes?
Nitazenes, also known as benzimidazole opioids, are a class of synthetic opioids that were first developed in the 1950s but have re-emerged in recent years as novel psychoactive substances. Reddit commentors report that these compounds act as mu-opioid receptor agonists, with potencies ranging from dozens to over one thousand times that of morphine, depending on the specific variant. Commonly discussed variants include protonitazene, metonitazene, isotonitazene, and newer N-pyrrolidino derivatives (such as metonitazepyne and protonitazepyne) and N-desethyl variants.

Public Health Impacts:
Multiple Reddit discussants report experiencing severe withdrawal symptoms from nitazenes, with some describing withdrawal as more intense than that from fentanyl or heroin. A consistent pattern across reports indicates rapid tolerance development, with discussants mentioning escalating doses over relatively short periods of use. Discussants frequently express concern about the extreme potency of these substances and the difficulty in achieving accurate dosing, particularly with compounds active in the sub-milligram range. Several commenters report unintentional exposure through contaminated drug supplies, including pressed pharmaceutical pills and other substances testing positive for nitazenes.

How is it Being Discussed?
Reddit discussions reveal a community generally aware of the serious risks associated with nitazenes, with experienced people who use nitazenes frequently warning newcomers about the dangers of these compounds. Discussants actively share harm reduction strategies, including volumetric dosing techniques, the use of test strips, and recommendations to avoid certain variants known for caustic properties. Some commenters describe attempting to use nitazenes as a substitute for fentanyl, citing economic factors or supply issues, though others strongly discourage this practice. Following the March 2025 UN scheduling action and various national bans, discussants mention difficulty obtaining certain variants and the emergence of new unscheduled alternatives. Multiple Reddit commentors report struggling with tapering and cessation, sharing experiences and seeking advice on managing withdrawal. Routes of administration are frequently discussed, with users comparing oral, intranasal, intravenous, and vaporized administration, often noting different potency profiles depending on route of administration.

Drug Terms:
Protonitazene, Metonitazene, Isotonitazene, N-pyrrolidino protonitazene (protonitazepyne), N-pyrrolidino metonitazene (metonitazepyne), N-desethyl isotonitazene, N-desethyl etonitazene, N-desethyl protonitazene, N-desethyl metonitazene, Etonitazene, Etonitazepyne, Butonitazene

Previous Reports:
April 5, 2024

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In the recently published 2025 World Drug Report from the United Nations Office on Drug and Crime (UNODC), the key findings reported that synthetic opioids, most notably nitazenes, have been emerging in some countries. The report notes that by 2024, more new nitazenes than new fentanyl analogues were being reported by Member States to the UNODC. In 2024, the most frequently identified nitazenes in forensic institutes worldwide were protonitazene, followed by N-pyrrolidino protonitazene, N-desethyl isotonitazene, and metonitazene. Read the key findings here.

Full United Nations Office on Drug and Crime 2025 World Drug Report

A recently published case study in the European Journal of Public Health by Abel-Ollo et al. examined the timeline of the nitazene epidemic in Estonia. The study employed a multifaceted approach to determine the prevalence and health consequences of nitazene use nationwide. The data conveyed that drug-related deaths in Estonia more than doubled since 2022, 39 to 80 cases, and exceeded over 100 cases in 2023. The study also notes an increased utilization of harm reduction services since 2022, with first responders facing growing challenges linked to the emergence of nitazenes. Read the article here.

A recently published study in the Journal of Forensic Sciences by Tishion et al. evaluated the metabolites of isotonitazene (ITZ) and metonitazene (MTZ) in postmortem cases. The study analyzed 27 cases, identifying N-desethyl isotonitazene (N-DI) as the most prevalent ITZ metabolite and N-desethyl metonitazene (N-DM) as the most common MTZ metabolite. The study also noted that fentanyl was the most prevalent co-detected substance. The findings suggest that N-DI and N-DM are suitable biomarkers for detecting nitazenes and highlight the need for their inclusion in routine testing protocols. Read the article here.

A recently published article in Nature by Basu discussed the emergence of nitazenes as a growing concern in the United States. The research highlighted that nitazenes have been increasingly detected in toxicology reports, particularly among individuals who use synthetic cannabinoids. The study found that the presence of nitazenes was associated with a higher risk of overdose and adverse health outcomes. Read the article here.

A recently published study in the Journal of American Society for Mass Spectrometry by Zhang et al. explored the fragmentation pathways of 17 nitazenes. The findings reveal that electron-activated dissociation techniques generate (EAD) more detailed fragmentation profiles than collision-induced dissociation (CID), aiding in the identification and characterization of small molecules. The study also identifies a novel nitazene in a seized sample, highlighting the value of CID and EAD in forensic toxicology workflows.Read the article here.

A recently published study in the Annals of Emergency Medicine by Roberts et al. examined the clinical experiences of confirmed nitazene opioid exposures. The study identified 27 laboratory-confirmed exposures in New South Wales, Australia, from June 2018 to March 2025. The most common route of exposure was vaping, and acute poisoning typically presented with sedation and hypoventilation. Naloxone was effective in reversing the effects, though repeat dosing was necessary in 45% of cases. The study highlighted the importance of ongoing monitoring to detect the reemergence of addiction and the need for public education and community access to naloxone to mitigate the harm posed by nitazene opioids. Read the full study here.

A recently published short communication in Drug Testing and Analysis by Kriikku et al. discusses fluetonitazepyne and isotonitazepyne as the latest additions to the group of nitazenes. The study reported five deaths in Finland where fluetonitazepyne was detected in post-mortem femoral blood at concentrations ranging from 0.4 to 9.5 μg/L, with a median of 1.7 μg/L. Isotonitazepyne was found in one case at a concentration of 1.4 μg/L. Other psychoactive substances were present in all cases. The study highlighted the importance of early recognition and communication of emerging substances to manage the public health threat posed by these potent opioids. Read the full study here.

A recently published study in Environmental Science & Technology by Subedi et al. highlights the utility of wastewater-based epidemiology (WBE) for detecting new psychoactive substances (NPS) at rest areas and commercial weigh stations along interstate highways. The study analyzed 547 samples collected over a 12-month period along Kentucky's interstate highways. The results from the study found several NPS, including first-time detections of metonitazene and p-fluorofentanyl. The authors determined from the results that the potential of WBE are an effective regional early warning system for NPS. Read the full article here.

A recently published articled in WIRED discussed the rise in overdose deaths linked to nitazenes across the US, Europe and Australia. The article states that the demographic most affected includes young adults and individuals with a history of substance use disorder. The author suggests that the increased potency of nitazenes poses a higher risk of overdose and death, even with small amounts, and underscores the need for enhanced monitoring, prevention and treatment strategies to address the evolving landscape of opioid misuse. Read the full article here.

Are you committed to advancing the science of substance use and public health? The University of Florida’s NIDA-funded T32 Training Program offers predoctoral and postdoctoral scholars an exceptional opportunity to launch impactful research careers focused on NDEWS!

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The NDEWS Weekly Briefing curates emerging data and findings from across the Early Warning Network, which includes three core components: our Scientific Advisory Group (SAG), comprised of national experts and federal partners; our Sentinel Site Directors (SSDs), who lead local surveillance in key geographic regions; and our Community-Based Health Experts, who provide on-the-ground insights from populations most impacted by drug trends. Together, these contributors generate timely, multidisciplinary and impactful information, ranging from peer-reviewed research findings to local surveillance data. These contributions inform public health and research communities.

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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:

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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), NYU Langone Health (MPI: Palamar), and Florida Atlantic University (Co-I: Barenholtz). Any item may be reproduced provided the source is acknowledged.