September 22, 2023

New Group of Synthetic Opioids Nitazenes Stronger Than Fentanyl and Connected to Overdose Fatalities

Table of Contents

Table of Contents

Contributors & Editors

Julie Miller

Addiction & Mental Health Writer

Last Update on September 22, 2023

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A recent study has highlighted the emergence of Nitazenes, a potent class of synthetic opioids potentially more powerful than the notorious Fentanyl.

As the opioid crisis in the U.S. continues to escalate, these new players in the illicit drug market pose an even greater risk.

With the capability to bypass existing Fentanyl regulations, the rise of Nitazenes underscores the urgency for public awareness and swift action.

This article delves into the details of the study and the implications of this emerging threat.


New Group of Synthetic Opioids Nitazenes Stronger Than Fentanyl and Connected to Overdose Fatalities


Research Indicates Emerging Synthetic Opioids Could Surpass Fentanyl in Potency

Recently discovered synthetic opioids might be more potent than Fentanyl, known to be 1,000 times stronger than Morphine.

They might necessitate multiple Naloxone (Narcan) doses to counteract an overdose, according to a recent study.1

During a 2020 press event, U.S. Attorney McGregor W. Scott showcased a Fentanyl sample camouflaged as Oxycodone, emphasizing the risks of Fentanyl and potential prevention measures.

Although Nitazenes resemble Fentanyl, they differ structurally.

The recent research in JAMA Network Open revealed that most patients who overdosed on Nitazenes required two or more Naloxone (Narcan) doses, unlike Fentanyl overdose victims who typically needed just one.2

The research team, spanning from the Icahn School of Medicine to Pennsylvania’s Lehigh Valley Health Network, stressed the importance for healthcare professionals to anticipate potential multiple Naloxone doses for Nitazene overdoses due to its increasing prevalence.

It’s believed that over 150 individuals succumb daily to overdoses linked to synthetic opioids.

Fentanyl plays a role in almost two-thirds of all such fatalities in the U.S., possessing a potency that’s 50 times greater than Heroin and 100 times that of Morphine.

However, Nitazenes, a new synthetic opioid subclass, could be even more dangerous, potentially leading to higher cardiac arrest rates during overdoses.

The research analyzed data from 537 adults brought to the emergency department for potential overdoses between 2020 and 2022 and underwent lab tests.

Out of these, 11 were confirmed to have taken only Fentanyl, while nine had exclusively ingested Nitazenes, including substances like Brorphine, Isotonitazene, Metonitazene, or N-Piperidinyl Etonitazene.

The study revealed that of those who overdosed on Nitazenes, 66.6% needed at least two doses of Naloxone, while only 36.4% of the 11 individuals who overdosed on Fentanyl required the same treatment.

Out of the 11 patients who overdosed on Fentanyl, CPR was administered to four.

In contrast, every individual who overdosed on the Nitazene variant, Metonitazene, received CPR.

Emergency intubation was necessary for half of the Metonitazene overdose cases, a stark comparison to the 27.3% for fentanyl-only overdoses.

Those overdosing on Metonitazene also demonstrated higher cardiac arrest and death rates.

Dr. Alex Manini, a contributor to the study, emphasized the urgency of enhancing harm-reduction policies in light of the dangerous synthetic opioids’ rise in the illicit drug market.

The study indicates that synthetic opioids like Fentanyl and Nitazenes are increasingly identified in overdose cases.

Joe Friedman from UCLA, not a participant in the study but familiar with the U.S. opioid crisis, stressed the importance of understanding these emerging drugs’ potential implications.

Sheila Vakharia from the nonprofit Drug Policy Alliance emphasized the uncertainty faced by users purchasing from the underground market, often misinformed about the substances they consume.

Newer opioids like Nitazenes have infiltrated the drug supply as suppliers seek alternatives to avoid stricter Fentanyl penalties.

Vakharia highlighted that Nitazenes’ popularity varies regionally, with notable increases in areas like Tennessee and Ohio.

Ohio Attorney General Dave Yost previously warned of Nitazenes as a rising synthetic opioid threat, urging the public and law enforcement to be vigilant.



Common Types of Nitazenes

Nitazenes belong to a class of synthetic opioids that have gained attention due to their high potency.3

Here are some common types of Nitazenes:

Opioid Name Properties Risks & Impact
Isotonitazene It is a highly potent opioid, reportedly 5 to 7 times as potent as Fentanyl. Isotonitazene has been associated with numerous overdose deaths and detected in illicit drug supplies.
Metonitazene It is a potent opioid agonist, exhibiting similar effects to other opioids. Due to its high potency, Metonitazene poses a significant risk of overdose and adverse effects.
Clonitazene It acts as an agonist at the mu-opioid receptor, producing pain relief and sedation effects. Clonitazene has been abused and misused, contributing to the ongoing opioid crisis.


It is important to note that the availability and prevalence of specific Nitazenes may vary over time and across different regions.

The emergence of new Nitazenes or variations on existing compounds is an ongoing concern and requires continuous monitoring by law enforcement agencies and healthcare professionals.

Using Nitazenes carries a high risk of addiction, overdose, and severe health consequences.

These potent substances contribute to the dire opioid crisis, necessitating comprehensive prevention, education, and treatment efforts.


Fentanyl vs Nitazenes

Fentanyl and Nitazenes are both synthetic opioids with powerful pain-relieving properties.
However, there are some differences between the two.

Aspect Fentanyl Nitazenes
Potency Fentanyl is highly potent, up to 50 times stronger than Heroin and 100 times stronger than Morphine. Nitazenes can be even more potent than fentanyl. According to a narrative review by NCBI, some Nitazenes are up to 1000-fold more potent than morphine.
Structural Differences Fentanyl has a unique structural identity. Nitazenes belong to the benzimidazole class of opioids. They are not structurally related to Fentanyl, meaning their chemical structures and interactions with brain receptors differ.
Illicit Drug Market Fentanyl has a significant presence in the illicit drug market. Nitazenes are emerging challenges in the illicit drug markets of North America and Europe. Their presence is increasing, albeit still relatively lower than Fentanyl.
Health Risks Fentanyl poses significant health risks, including overdose and addiction. Its synthetic nature makes it highly potent, leading to a higher overdose risk than other opioids. Nitazenes also present considerable health dangers, like overdose and addiction. Due to their potency and structure, they can be especially hazardous.


How Will This Impact The Opioid Crisis?

In the shadowy realms of the illicit drug market, particularly in North America and Europe, Nitazenes are steadily gaining traction.

Despite their current lower prevalence compared to Fentanyl, their emergence signifies the introduction of another perilous opioid in an already critical situation.

The Opioid Crisis has seen a surge in overdose deaths, predominantly due to Fentanyl.

The arrival of Nitazenes, with their superior strength, suggests that fatalities might climb even higher.

This is further compounded by the possibility that the heightened potency of Nitazenes could make it harder to counteract overdoses with conventional Naloxone doses.

This dynamic also introduces added challenges for substance abuse treatment programs and healthcare providers.

The advent of hyper-potent opioids such as Nitazenes necessitates innovative harm reduction, prevention, and intervention approaches.

Therefore, it is imperative for stakeholders, including healthcare professionals, law enforcement, and policymakers, to escalate their vigilance.

Initiatives must encompass increased public education, augmented access to treatment services, fortified law enforcement protocols, and the adoption of harm reduction techniques.

The ramifications of nitazenes in the opioid crisis underscore the need for continuous surveillance, extensive research, and combined efforts to safeguard public health.


Treatment Challenges and Strategies

Dealing with the opioid crisis is difficult due to the complexity of addiction patterns, socioeconomic factors, and constantly changing drug misuse.

Introducing more potent opioids such as Fentanyl and Nitazenes adds to the challenge as they require unique medical and therapeutic approaches due to their potency.4

To counter the deep-seated opioid crisis, a holistic approach is vital, emphasizing prevention, therapeutic measures, and minimizing harm.

This involves enhancing the availability of scientifically-backed addiction treatments, promoting Naloxone distribution to counteract overdoses, introducing medication-driven treatment schemes, and bolstering public consciousness about opioid misuse’s dangerous nature.

These strategies should also address the broader societal and systemic issues contributing to the crisis.

By fully comprehending the magnitude of the crisis, spotlighting the influential role of Fentanyl, and being vigilant about emerging threats like Nitazenes, collective efforts can be geared towards alleviating the profound effects and preserving lives.

If you or a loved one is struggling with addiction, we’re here to support you!

At Cornerstone Healing Center in Scottsdale, AZ, we pride ourselves on our holistic approach to healing, emphasizing inner well-being for enduring recovery.



[1] Emerging group of synthetic opioids may be more potent than fentanyl, study warns

[2] Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients

[3] Old Drugs and New Challenges: A Narrative Review of Nitazenes

[4] New Synthetic Opioids: Clinical Considerations and Dangers

Published: 9/22/2023

Contributor: Julie Miller

Editor: Susana Spiegel

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Author & Reviewers

julie miller recovery writer and author
Julie is a recovery advocate, with over two years sober. She is a recovery speaker who believes people can change for the better. Her mission is to write factual, helpful information about addiction, treatment, and recovery. She believes that no one should be left in the dark about the process at any stage of their recovery.
lionel estrada lisac clinical director

Lionel is the Clinical Director of Cornerstone’s treatment facilities in Arizona. He has had over 4 years at Cornerstone. He is personally in recovery and passionate about helping others overcome substance abuse and mental health challenges, he is trained as an EMDR, adopting a trauma-informed approach to treat the underlying issues of conditions.

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