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  • Writer's pictureDr. Harold Pierre

Nitazenes Opioid Street Drugs, 43 Times More Potent Than Fentanyl

Urgent Warning: Nitazenes, the New Street Opioid Drug Deadlier Than Fentanyl


The New Threat in the Opioid Crisis


The opioid epidemic has reached a new level of danger with the rise of nitazene, a synthetic opioid class that surpasses even fentanyl in potency. This piece focuses on nitazene, a name increasingly associated with significant risks in drug misuse and public health concerns. It's crucial to grasp the seriousness of this issue. Often concealed within the illicit drug trade, nitazene presents a unique problem. Its deadly strength, a lack of testing to identify it in urine drug tests, coupled with the lack of awareness among drug consumers, amplifies its threat.


As we navigate through this comprehensive exploration, we will compare nitazene to fentanyl, illustrating the alarming increase in potency and the consequent risks. We will examine the insidious rise of nitazenes in the illicit drug market, its clinical and public health implications, and the available treatment options for addiction. Our discussion is not just an academic exercise; it is an urgent warning and a call to action for awareness, preparedness, and response to this new and deadly wave in the ongoing opioid epidemic.


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Comparing Nitazenes and Fentanyl: Understanding the Increased Potency


The opioid crisis has been dominated by the devastating impact of fentanyl for years, but the arrival of nitazene marks a concerning escalation. To comprehend the severity of nitazene’s threat, it's crucial to compare it with fentanyl, previously considered one of the most potent opioids in the illicit drug market.


Nitazenes, a group of synthetic opioids, has been found to be significantly more potent than fentanyl. This increased potency is not merely a numerical difference; it translates into a higher risk of overdose and fatalities. Unlike fentanyl, which itself is 50 to 100 times more potent than morphine, nitazene compounds can be several times more potent than fentanyl, leading to an alarming increase in overdose deaths. The lethality of Nitazenes lies in its ability to depress respiratory functions at lower doses than fentanyl, making it deadlier even in minuscule quantities.


The danger of nitazenes is compounded by its clandestine presence in the drug supply. Often, users are unaware that it is added in what they believe to be heroin or fentanyl, leading to accidental overdoses. The unpredictability of its potency, coupled with the lack of public awareness, contributes to the rising nitazene-related deaths.


The Emergence of Nitazenes in the Illicit Drug Market


The emergence of nitazenes in the illegal drug market marks a troubling evolution in the opioid epidemic. Their introduction signifies more than just a surge in potency; it represents a transformation in the production and distribution of synthetic opioids. The black market is moving away from fentanyl.


Originally developed for medicinal purposes in the 1950s, nitazenes belong to the wider class of benzimidazole opioids. They were never approved for medical use due to their extreme potency and high potential for abuse. They are classified as Schedule I drugs by the Drug Enforcement Administration (DEA), meaning that they have no medical use.


Nevertheless, starting around 2019 these compounds have carved out a niche in the illegal drug arena. The relatively simple and cost-effective production process of nitazenes makes them appealing to illicit drug producers who aim to enhance the strength of their offerings.

There are 5 common nitazenes found in street drugs:


  • Isotonitazene (ISO): Initially identified in illicit drugs in 2019, ISO remains a major concern due to its extreme potency, estimated to be 20-50 times more potent than fentanyl. It's often mixed into other drugs like heroin and cocaine to increase their potency, leading to unsuspecting overdoses.

  • Metonitazene: This nitazene gained notoriety in 2020, 2021, and 2022, particularly in Tennessee, where it surpassed isotonitazene as the most common cause of nitazene-involved deaths. While not as potent as other nitazenes, its potency is still 100 times that of morphine.

  • Etazene: This nitazene, while less frequently detected than others, has been linked to overdose deaths in the United States and Europe. Its potency is comparable to ISO, making it highly dangerous.

  • N-phenethyl-4-piperidinol (NPP): Though not as widely reported as others, NPP has emerged as a nitazene of concern in recent years. Its potency is comparable to fentanyl, and its presence in illicit drugs has been linked to overdose deaths.

  • Etonitazene: Estimated to be 1,000 to 1,500 times more potent than morphine in animal studies. This means it is significantly stronger than fentanyl and also carries a much higher risk of overdose and fatalities.


Nitazenes are often mixed with other substances like heroin or sold as fentanyl, unbeknownst to users. This deceptive practice dramatically increases the risk of overdose, as even seasoned opioid users may not be prepared for its extreme potency.


As nitazenes continues to permeate the illicit drug market, understanding its origins, production, and distribution becomes vital. This knowledge is crucial not only for Drug Enforcement Administration (DEA) in their efforts to curb the spread but also for public health initiatives aimed at educating potential users about the dangers of this new and deadly opioid.


Clinical and Public Health Implications of Nitazenes Use


The emergence of nitazenes in the opioid crisis presents significant challenges for both clinical practice and public health. Its potent nature and unpredictable presence in the drug supply have far-reaching implications, necessitating a multifaceted response from healthcare providers, emergency responders, and public health officials.


From a clinical standpoint, the treatment of nitazenes overdose poses unique challenges. Due to its higher potency compared to fentanyl, traditional methods of overdose reversal, Narcan (naloxone), may be less effective. This situation often requires multiple doses of naloxone, the standard treatment for opioid overdose, and sometimes more advanced medical interventions. Healthcare providers must stay vigilant and prepared for these complex cases.


For public health authorities, the rise of nitazenes exacerbates the already critical opioid epidemic. The increased risk of overdose and death necessitates enhanced surveillance and reporting systems to track the prevalence and impact of nitazenes. Public health campaigns must also adapt, focusing on raising awareness about the specific dangers of nitazenes, promoting harm reduction strategies, and providing accurate information to those at risk.


The broader implications of nitazenes use extend to societal concerns such as increased healthcare costs, the burden on emergency services, and the tragic toll on families and communities. These factors underscore the urgent need for a coordinated response that includes not only medical treatment and law enforcement but also education, community engagement, and policy initiatives aimed at addressing the root causes of opioid abuse and addiction.


Treatment Options for Nitazenes Addiction


Addressing Nitazenes addiction requires a nuanced and multifaceted approach, given the drug's extreme potency and the complexities of opioid addiction treatment. As with other opioids, the journey to recovery from Nitazenes addiction involves a combination of medical, psychological, and social support strategies.


Treating opioid addiction, especially when it involves Nitazenes, relies heavily on Medically-Assisted Treatment (MAT). This approach typically employs Federal Drug Administration-approved medications like methadone, buprenorphine, and naltrexone. These drugs aim to stabilize brain chemistry, counteract the euphoric effects of opioids, reduce cravings, and avert withdrawal symptoms. Combined with extensive counseling and behavioral therapies, this comprehensive strategy is vital for successful treatment and sustainable recovery.


Desperate. Sad man. Man experiencing difficulties in life copy

Nevertheless, the extraordinary potency of nitazenes introduces extra complexities. Due to its high potency, buprenorphine, methadone and possibly naltrexone doses may need to be significantly higher than the standard of care. Also, while the half-life of ISO in rats is 1 hour, there aren't well defined data in humans. Thus, transitioning to a buprenorphine based MAT may be challenging. Treatment plans should be meticulously supervised and customized to each individual's requirements. In certain scenarios, increased dosages or extended medication periods might be essential for effectively managing withdrawal symptoms and curbing cravings.


Beyond medical treatment, successful recovery from nitazenes addiction also involves addressing the psychological and social aspects of addiction. This includes ongoing counseling, support groups, and therapy sessions that address the root causes of addiction, coping strategies, and relapse prevention. Social support systems, including family involvement and community resources, play a critical role in providing a supportive environment for recovery.


Conclusion: The Urgent Need for Awareness and Action


The emergence of nitazenes as a drug of abuse carries significant clinical and public health consequences. This situation demands a ramp-up in medical readiness, refinement of addiction treatment protocols, and intensified public health initiatives that emphasize education and harm reduction. It's crucial for healthcare professionals, emergency responders, and public health officials to be well-equipped with the appropriate tools and knowledge to effectively confront this growing challenge.


Furthermore, combating nitazenes addiction requires a multifaceted approach extending beyond the realm of healthcare. This includes broad policy measures, law enforcement actions to cut off the supply of these drugs, and community-driven programs aimed at prevention, treatment, and recovery. Educating the public and raising awareness are key in curtailing the proliferation of nitazenes, thus lowering the incidence of overdoses and fatalities.


Pergolizzi Jr, J., Raffa, R., LeQuang, J. K., Breve, F., & Varrassi, G. (2023). Old drugs and new challenges: A narrative review of nitazenes. Cureus, 13(6). https://doi.org/10.7759/cureus.40736


Walton, S. E., Krotulski, A. J., Glatfelter, G. C., Walther, D., Logan, B. K., & Baumann, M. H. (2023). Plasma pharmacokinetics and pharmacodynamic effects of the 2-benzylbenzimidazole synthetic opioid, isotonitazene, in male rats. Psychopharmacology (Berl), 240(1), 185-198. https://doi.org/10.1007/s00213-022-06292-5


Tsai, M. H. M., Chen, L., Baumann, M. H., Canals, M., Javitch, J. A., Lane, J. R., & Shi, L. (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. https://doi.org/10.1101/2023.11.10.566672


About the author: 

Dr. Harold Pierre is a board-certified anesthesiologist and addiction medicine specialist with over 20 years of experience. He is certified by the American Board of Anesthesiology and the American Board of Preventive Medicine.



This website is provided for educational and informational purposes only and does not constitute providing medical advice or professional services. The information provided should not be used for diagnosing or treating a health problem or disease, and those seeking personal medical advice should consult with a licensed physician or another qualified medical professional. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.







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