While fentanyl has dominated the opioid crisis, a new, older class of synthetic opioids is emerging in Colorado’s Front Range. Have you ever heard of nitazines?
If not, you should be aware, as Colorado’s Department of Public Health and Environment has documented nitazene‑involved deaths across multiple Front Range counties, with at least 13 deaths between August 2021 and October 2023 [1].
State and local officials emphasize that nitazenes appear in powdered opioids and counterfeit tablets and that people may think they are buying “just” fentanyl, heroin, or pain pills.
In Boulder County, two overdose deaths involved nitazenes. One case was with etonitazene (a new analog or variant), highlighting that local supply is changing and chemists are modifying the base structure of a nitazene, adding some things onto it to create different analogs to stay ahead of the DEA.
Although still rare, nitazenes represent a significant escalation in the opioid crisis due to their extreme potency, their ability to evade detection, and the unique clinical challenges they pose to first responders and medical examiners. Unfortunately, their presence is expected to increase.
In this article, I explain what they are, their presence in Colorado, their risks, challenges in potency and detection, and the role of naloxone and harm reduction strategies.
What Are Nitazines?
Nitazenes are a class of synthetic opioids that can have potencies of up to 500 (or more) times that of heroin. They can be readily manufactured in illicit labs at low cost.
These potent synthetic opioids were originally synthesized in the 1950s and 60s for use in humans for pain management, but their development was halted due to extreme potency. They have never been approved for medical use. But around 2019, they reappeared in the illicit drug market.
Nitazenes are 2‑benzylbenzimidazole opioids. They act as full mu‑opioid receptor agonists, similar to heroin and fentanyl, but some analogs (e.g., N‑desethyl isotonitazene, etonitazene) show substantially higher potency than fentanyl.
Small changes in their chemical side chains can markedly change potency, leading to many different analogs in the illicit market. This makes it very difficult to track and keep up with the variations of this very deadly drug.
They are structurally different from fentanyl and morphine; as such, they don’t show up on standard toxicology or field test kits.
Nitazene Deaths in Colorado
The Colorado Department of Public Health and Environment says the state has had 13 deaths related to nitazenes since 2021, between August 2021 and October 2023, all occurring along the Front Range (Larimer to El Paso counties) [2].
In Denver, there were five deaths tied to a nitazene compound in 2022, but none in 2023, according to the city’s Office of the Medical Examiner.
In El Paso County, there have been four deaths related to the synthetic opioid from late 2022 through December 2024, according to Coroner Dr. Leon Kelly. [3]
In Boulder County, in the latter half of 2023, two men, 20 years old and 22 years old, died of overdoses on nitazene or its variants. One victim, a student, purchased what he thought was Xanax from the dark web, and a unique nitazene analog was detected that had never been seen before in the U.S. [4].
Users rarely seek out nitazenes; they are usually adulterants found in counterfeit oxycodone, alprazolam, heroin, fentanyl, methamphetamine, illicit benzodiazepines, counterfeit pills, or other substances.
Potency and Overdose Risk
While fentanyl is roughly 50x more potent than heroin, animal studies suggest several nitazenes can be 7–30+ times more potent than fentanyl, with variations like etonitazene being up to 500x more potent than heroin [5].
Because these drugs are so potent, the margin between a therapeutic dose and a lethal dose is terrifyingly small.
In practice, post‑mortem concentrations in humans appear similar to fentanyl, but studies show severe toxicity, frequent respiratory arrest, and prolonged effects for some variations, such as metonitazene and etonitazene. Animal studies suggest nitazenes may cause prolonged respiratory depression requiring extended monitoring
Nitazenes are usually not taken intentionally; they are often used to adulterate heroin, fentanyl, counterfeit pills, or other drugs, so people frequently do not know they are exposed.
We don’t know the full scope of nitrazine’s impact due to difficulties in detection, which causes forensic challenges. Nitazenes are missed in standard drug testing panels. The Boulder County Coroner only identified the drug by sending samples to a specialized forensic research lab.
A 2026 report in the UK shows that nitazenes degrade rapidly in post-mortem blood samples, meaning death counts may be underestimated by as much as one-third [6].
Naloxone: Does It Work?
Nitazenes are still opioids, and naloxone (Narcan), as a competitive opioid antagonist, does work. Multiple clinical and pharmacologic reviews state that naloxone can reverse nitazene‑induced respiratory depression.
However, studies show that patients with nitazene overdoses more often require multiple or higher‑than‑usual (1.2 mg vs the standard 0.4 mg) naloxone doses. Some patients require continuous infusions and extended observation or hospitalization. (e.g., hundreds of hours for metonitazene in one review), indicating prolonged or recurrent toxicity [7].
Always call 911, administer Narcan immediately, and be prepared to use a second dose.
Harm‑reduction Recommendations
For people who use drugs, work in frontline programs, and clinicians in Colorado:
- Expect contamination: Assume that illicit opioids (powders and pills) may contain nitazenes, even if sold as fentanyl, heroin, or oxycodone. Colorado Public Health officials stress that the unregulated market means users can never be sure what is in their substance.
- Emphasize testing and safer use: Promote fentanyl test strips where legal (though they don’t detect all nitazenes) and emerging nitazene‑capable drug checking. Use with others present, start with a very small amount, and avoid mixing with other CNS depressants [8].
- Plan for higher naloxone needs: Encourage carrying multiple doses; in clinical settings, be ready for repeat dosing, airway support, and extended monitoring after reversal. [9]
- Integrate OUD care: Given their high potency, nitazenes reinforce the need for rapid access to medications for opioid use disorder (buprenorphine, methadone, XR‑naltrexone) and linkage from emergency departments or outreach settings.
- Law Enforcement: The DEA has recently emergency scheduled several nitazene analogs, but chemists constantly create new variants to stay ahead of the law.
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Sources
[1] Colorado Consortium for Prescription Drug Abuse Prevention. nd. Nitazene links.
[2] Breen C. 2023. What are nitazenes? What to know about the drug that can be 10 times as potent as fentanyl. CBS News. Dec. 21, 2023.
[3] Prentzel O. 2024. Rare street drug that could be more potent than fentanyl surfaces in Boulder County. The Colorado Sun. Jan 5, 2024.
[4] Abeyta M. 2023. Nitazenes, opioids “more potent than fentanyl,” related to 2 recent Colorado deaths. CBS News. Dec. 29, 2023.
[5] Tsai, M. et al. (2023). The in vitro functional profiles of fentanyl and nitazene analogs at the μ-opioid receptor – high efficacy is dangerous regardless of signaling bias. bioRxiv : the preprint server for biology, 2023.11.10.
[6] Kings College London. 2026. UK’s growing synthetic opioid problem: Nitazene deaths could be underestimated by a third. Eurekalert.org.
[7] Berger J., et al. 2025. Naloxone Dosing and Hospitalization for Nitazene Overdose: A Scoping Review. J Med Toxicol. 2025 Apr; 21(2):276-283.
[8] Schwarz, E., et al. (2025). Nitazenes: An Old Drug Class Causing New Problems. Missouri medicine, 122(4), 329–333.
[9] Amaducci A, et al. Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients. JAMA Netw Open. 2023; 6(8)