The Recent Surge of Nitazenes
- Arun Gupta, MD
- Sep 27
- 6 min read
Tom O'Connor, Author & Publisher
Reviewed by Arun Gupta, MD, PC, Subject Matter Expert
Our esteemed Subject Matter Expert, Dr. Arun Gupta, is a leading figure in the field of addiction medicine. His extensive experience and research, culminating in the comprehensive guide 'The Preventable Epidemic: A Frontline Doctor's Experience and Recommendations to Resolve America's Opioid Crisis', make him a trusted source in this critical area.
Nitazenes are a class of highly potent synthetic opioids that are often more dangerous than fentanyl. Initially developed in the 1950s as a potential alternative to morphine, they were never approved for medical use due to their high potential for overdose. Beginning around 2019, nitazenes re-emerged on the illicit drug market and have since been linked to hundreds of overdose deaths in the Americas and Europe.
Extreme Potency and Overdose Risk
Some nitazene analogs, such as isotonitazene, are estimated to be hundreds or even thousands of times more potent than morphine and significantly stronger than fentanyl. Their high potency poses an extreme risk of overdose, which can happen with minimal warning due to the tiny dose required to produce an effect.
Nitazenes are a class of highly potent synthetic opioids that have emerged in the illicit drug supply and are a serious public health threat. Initially developed in the 1950s as a potential pain medication, they were never approved for medical use due to their high potential for addiction and overdose.
Dangers and Risks
High potency: Some nitazenes are significantly more potent than heroin and fentanyl, making the risk of a fatal overdose extremely high. For example, the nitazene isotonitazene (ISO) is 250 to 900 times stronger than morphine.
Respiratory depression: Like other opioids, nitazenes depress the central nervous system, which can cause breathing to slow or stop entirely. This is the primary cause of overdose deaths.
One of the most alarming aspects of nitazenes is their frequent inclusion in other illicit drugs, such as heroin, cocaine, counterfeit pills, and methamphetamine. This clandestine practice significantly heightens the risk of an overdose, as users are often unaware of the presence or strength of nitazenes in the drugs they are consuming.
Addiction and withdrawal: Nitazenes are highly addictive. Withdrawal symptoms can be severe and painful, similar to those experienced with other potent opioids.
Overdose requires more naloxone: While the opioid overdose reversal agent naloxone is effective against nitazene overdoses, the high potency often requires multiple, larger doses to reverse the effects. Naloxone works by binding to the same receptors in the brain as opioids, blocking the effects of opioids and reversing the overdose.
Emergence and Regulation
Recent surge: After being largely absent from the illicit market for decades, nitazenes began to reappear around 2019.
The global spread of nitazenes is a cause for concern. Reports of these dangerous substances have increased worldwide, with countries like the United States, Canada, and several in Europe reporting the highest numbers of different nitazene analogues. This underscores the urgent need for international cooperation in combating this threat.
Evolving market: Illicit manufacturers continually create new chemical versions (analogues) of nitazenes to evade drug laws and detection methods, contributing to an expanding list of these dangerous substances. This constant evolution poses a significant challenge to law enforcement and regulatory agencies in their efforts to control the spread of nitazenes.
Legal status: Many nitazenes have been scheduled as controlled substances in the US and other countries.
Key Facts Proving Nitazenes are Dangerous
Decades of research. Pharmaceutical researchers first synthesized Nitazenes in the 1950s as a potential alternative to morphine. However, they were deemed too dangerous for medical use because of their high potency and addiction potential and were never approved. For decades, they remained confined mainly to specialized research, and most medical providers were unaware they existed.
Widespread detection and overdose deaths. Beginning around 2019, nitazenes started to emerge in illicit drug supplies in Europe and North America. Since then, numerous overdose deaths have been linked to these drugs across multiple continents. In the U.S., cases of nitazene-involved overdose deaths have been documented in various states, including Tennessee and Colorado.
Extreme potency. Specific nitazene variants are significantly more potent than fentanyl. For example, some analogs can be 10 to 40 times stronger than fentanyl and hundreds or even thousands of times more powerful than morphine. This extreme potency makes a fatal overdose possible with a minimal amount, potentially less than a grain of salt.
Often hidden in other drugs. A significant danger is that nitazenes are frequently mixed into other illicit drugs, such as fentanyl, heroin, or counterfeit prescription pills. Many users may unknowingly be consuming nitazenes, dramatically increasing their risk of a fatal overdose.
Difficult to detect. Standard toxicology screenings and fentanyl test strips do not typically detect most nitazene analogs. Specialized, advanced laboratory testing is required to identify them, which can make it difficult for medical professionals to know what they are dealing with during an overdose event.
International law enforcement and government warnings. Agencies worldwide are actively warning about the threat of nitazenes. The U.S. Drug Enforcement Administration (DEA) has issued warnings and, in 2020, classified the most prevalent nitazene, isotonitazene (ISO), as a Schedule 1 substance. Authorities in the U.K. and Australia have also issued official alerts about the drug's dangers.
Treatment for Nitazene Overdose
Naloxone (Narcan) can reverse a nitazene overdose, but its effectiveness may be reduced, and special precautions are necessary.
Multiple doses needed: Because of their high potency, nitazene overdoses often require multiple doses of naloxone to reverse.
Prolonged effect: Some nitazenes may have a longer duration of action than fentanyl, potentially requiring more naloxone and a more extended treatment period.
Given the high potency of nitazenes, immediate medical attention is crucial in the event of an overdose. The use of naloxone, in addition to emergency medical services (EMS), is essential and can significantly increase the chances of survival.
Regulation and Surveillance
Responding to the growing threat, law enforcement and health agencies worldwide are taking action against nitazenes.
International control: Several nitazene compounds are being placed under international control.
Scheduling: Many countries have specifically outlawed nitazene compounds. For instance, the U.S. Drug Enforcement Administration (DEA) has classified several nitazenes, such as isotonitazene (ISO), as Schedule I substances.
Genetic (Generical) definitions: Some governments, including the UK and China, have passed legislation that generically defines and bans all compounds derived from the core nitazene structure, which helps to regulate future analogs that may appear.
Limited surveillance: Due to their clandestine nature and recent market introduction, comprehensive data on nitazene use is restricted, although surveillance efforts are improving.
According to Arun Gupta, MD
I wrote about these products in my book, The Preventable Epidemic: A Frontline Doctor's Experience and Recommendations to Resolve America's Opioid Crisis.
More than three years ago, we were unable to identify or isolate these agents clinically. Now we witness it and experience it. Standard drug testing still does not identify these drugs, but they are isolated during autopsy most of the time. Other standard features include that people abusing Nitazenes analogs, isotonitazene, are found in overdose patients, with past or current abuse of fentanyl and xylazine, and a recent change in social status to homelessness. They typically are hepatitis C positive and have a history of multiple overdoses in the past.
The recent HALT passed by the federal government, the bipartisan Legislation, formally titled the HALT All Lethal Trafficking of Fentanyl Act, permanently classifies fentanyl related substances(FRS) as Schedule 1 drugs under the Controlled Substances. This bill passed the US House of Representatives by a vote of 322-104. Signed July 2025.
My concerns are.
Does the HALT act include Nitazenes analogs, like isotonitazene?
THC, marijuana, is also a Class 1 drug in America, but is legal or decriminalized in 34 States, which means that there is a disconnect in the classification of drugs, and the laws are very soft on Class 1 drugs.
Twenty-five years ago, doctors were accused of running pill mills and were responsible for over-prescribing prescription medications like OxyContin, which was responsible for overdose deaths.
Over the past 15 years, Heroin, Fentanyl, Xylazine, Cocaine, Methamphetamine & Nitazenes analogs, like isotonitazene, have been virtually accountable for 100% of the overdose deaths in America in the last 5 years. Death Rates have consistently stayed over 100,000 annually during this period. Why?
We need to treat addiction as any other chronic disease and not a moral failing. We are not making much progress in that space.
We need large institutions to accept, support, and finance MAT (medication-assisted treatment).
We need to change the Medical school curriculum so that ALL doctors are trained in addiction medicine, not just a handful.
We must create mandatory education to reduce STIGMA on the following topics: better vocabulary, empathy, and humanity.
Arun Gupta, MD, PC, Subject Matter Expert, has practiced medicine for 35 years. Throughout decades of treating addiction patients, he has seen firsthand the devastation and heartbreak caused to their families. He recently formed the SOS Foundation, a non-profit focused on resolving the opioid crisis. The foundation's initiatives include [specific initiatives], and it has [specific achievements]. Dr. Gupta is a highly sought-after speaker and an American Society of Addiction Medicine (ASAM) certified Addiction Provider and Certified Medical Review Officer.
If you enjoyed this article,
Please forward this to a friend or colleague who might benefit from it!
Comments