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Nitazenes: A Dangerous Class of Synthetic Opioids

By: Kailyn Tomilin MPH

Background

Nitazenes are a class of synthetic opioids that pose serious risk to health and have caused a significant number of deaths1. One notable characteristic of nitazenes is their potency, which is over tenfold the potency of fentanyl and hundredfold the potency of morphine2. While their re-emergence has become an increasing concern in recent years, nitazenes are older opioid analgesic drugs originally developed in the 1950’s but never approved for market use1. Due to the inexpensive manufacturing and availability, they are a popular street drug1. Nitazenes are sometimes referred to by nicknames such as “Iso” or “Tony”1.

 

Some of the drugs included in the nitazene subgroup including etonitazene, isotonitazene, clonitazene, and several additional nitazene analogs are listed as Schedule I substances under the Controlled Substances Act2. However, an increased popularity of synthetic opioids among PWUD and a lack of scheduling for several drug compounds increases the risk of overdose.

Effects

Nitazenes, chemically known as 2-benzylbenzimidazoles opioids, act on the mu-opioid receptors similarly to drugs like heroin and fentanyl3. Due to their potency and street appeal, nitazenes are often compared to fentanyl, however they differ structurally2. People may use nitazenes for the short-term effects of relaxation, pain relief and mood enhancement3. However, there are many negative effects associated with nitazene use including nausea, slowed breathing, fever, and sweating. Like other opioids, long-term use of nitazines can lead to dependence and increased tolerance3. Nitazene overdose can cause adverse health effects including respiratory issues, seizures, brain damage and other serious complications4. Research has shown that prolonged respiratory depression is one of the major side effects associated with nitazene use, which typically lasts longer than the respiratory effects of fentanyl3.

 

The most common route of administration is injection, though other routes can include smoking, snorting, and ingestion5.

Treatment

The re-emergence of nitazene drugs has led to increased overdose deaths in recent years. The Centers for Disease Control and Prevention’s Mortality and Morbidity Weekly Report (MMWR) data showed an increase in the number of nitazene-involved deaths between 2019 and 2021 in Tennessee5. In 2019, there were no deaths linked to nitazenes, however, that number jumped to 10 deaths in 2020, and rose again to 42 deaths in 2021—a fourfold increase in just one year5. According to the DEA’s National Forensic Laboratory Information System, there have been over 4,300 reports of benzimidazole opioids in the U.S. since 20192. The actual number of nitazene-involved deaths is thought to be underestimated due to a low frequency of testing5.

 

To treat a suspected nitazene overdose, the CDC recommends administering naloxone5. Due to the high potency of the drug, longer periods of observation may be necessary in the event of additional naloxone dosing5.

Resources

To learn more about opioids and other drugs, you can access articles and educational materials on the MATTERS website. Resources can be found at https://mattersnetwork.org/edu/ and https://mattersnetwork.org/news/. Order free harm reduction supplies, including naloxone, on our website or mobile app.

References

  1. Pergolizzi J Jr, Raffa R, LeQuang JAK, Breve F, Varrassi G. Old Drugs and New Challenges: A Narrative Review of Nitazenes. Cureus. 2023;15(6):e40736. Published 2023 Jun 21. doi:10.7759/cureus.40736
  2. Drug Enforcement Agency. (n.d.). Isotonitazene. https://www.deadiversion.usdoj.gov/drug_chem_info/isotonitazene.pdf
  3. Malcolm NJ, Palkovic B, Sprague DJ, et al. Mu-opioid receptor selective superagonists produce prolonged respiratory depression. iScience. 2023;26(7):107121. Published 2023 Jun 13. doi:10.1016/j.isci.2023.107121
  4. Kozell LB, Eshleman AJ, Wolfrum KM, et al. Pharmacologic Characterization of Substituted Nitazenes at μκ, and Δ Opioid Receptors Suggests High Potential for Toxicity. J Pharmacol Exp Ther. 2024;389(2):219-228. Published 2024 Apr 18. doi:10.1124/jpet.123.002052
  5. Centers for Disease Control and Prevention. (2022, September 15). Notes from the field: Nitazene-related deaths – Tennessee, 2019–2021. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/volumes/71/wr/mm7137a5.htm