What Is Isotonitazene and Why Is It Dangerous?

Synthetic opioids such as fentanyl and oxycodone have become major drugs of abuse over the last decade. One of the newest drugs to emerge is isotonitazene, which can be deadly for first-time users. It’s part of a growing trend of novel synthetic opioids appearing on the black market and poses a significant challenge for public health and law enforcement agencies.

Read more to learn why some are calling this synthetic pain medication the “new fentanyl.”

What Is Isotonitazene?

Since the late 80’s, the United States has faced a growing opioid crisis, characterized by fatal overdoses in the tens of thousands each year. For most of the last decade, synthetic opioids like fentanyl and oxycodone have been the most dangerous drugs of the crisis.

Since the Chinese ban on fentanyl production in 2019 and increasing US regulation on Oxycodone production, several new opioids have entered the illicit drug market. One of the newer synthetic opioids to emerge is isotonitazene.

First synthesized in the 1950s, isotonitazene comes in both tablet and powder form. Originally, the drug was part of the pharmaceutical industry’s attempt to develop safer opioid medications. Isotonitazene, commonly referred to on the street as “ISO,” belongs to a chemical class of nitro benzimidazoles. In medical settings, this class of compounds is often used for its antimicrobial properties.

More importantly, isotonitazene is the first opioid of this class to be discovered on the black market in recent years. Unfortunately, the differences in the drug’s chemical structure complicates efforts to treat overdoses from fentanyl or other opioids contaminated with ISO.

How Potent is Isotonitazene?

ISO is significantly more potent than more traditional opioids like morphine, and has been associated with the risk of fatal overdose, similar to other opioids. A study in mice found ISO to be significantly more potent than morphine. And according to in vitro pharmacological evidence, it’s 20 times as potent as fentanyl.

Due to its potency, difficulty of detection, and increasing availability, some have labeled isotonitazenethe “new fentanyl.”

Since its appearance in the US in 2019, at least several hundred deaths have been attributed to Isotonatizene. In an effort to deal with this new threat, it has temporarily been made a Schedule I drug by the US Attorney General. This designation will last for two years while new legislation to address it is pending.

Perhaps the worst part: studies show that patients who overdosed on fentanyl mixed with ISO, compared to just fentanyl alone, required more naloxone (Narcan) to be resuscitated. This makes synthetic opioids mixed with ISO more resistant to the actions of first responders.

Isotonitazene in the News

Law enforcement data indicates that isotonitazene is increasingly prevalent in the United States illicit drug market. In April 2019, the United States Customs and Border Protection seized 1.6 grams of isotonitazene in California.

Since then, it has shown up across California, in places such as San Francisco and Santa Rosa. Worldwide, it has continued to increase in prevalence, according to 2024 data from the United Nations Office on Drugs and Crime.

Isotonitazene has been called the new fentanyl due to how potent it is. Some reports have called it 20 to 100 times more potent than fentanyl. While direct comparisons are difficult, it’s  safe to say it’s much more potent than both morphine and oxycodone.

Like other opioids, isotonitazene can cause respiratory depression, where breathing becomes shallow or stops altogether. This is the primary cause of fatal opioid overdoses. The risk is higher with more potent synthetic opioids like isotonitazene.

This high potency, combined with the fact it’s often marketed by dealers as being some other, less potent opioid, means an unsuspecting user runs a high risk of overdose.

What Does the Science Say?

According to a study taken in Milwaukee and Chicago, over a one-and-a-half-year period there were 40 ISO-related deaths – 4% of the total deaths from synthetic opioids as a whole. Since then, ISO has been causing between 40 to 50 deaths a month, with several hundred deaths per year.

While that figure may not seem like a lot, compared to the thousands that die of fentanyl or other opioids, it’s important to keep in mind that Isotonitazene is very new on the scene. As a result, only a few jurisdictions routinely test for it in overdose cases. Therefore, while we can’t know the full extent of ISO’s danger, it’s certainly not “safe” by any means.

It’s also worth noting: when fentanyl first emerged in the early-2010’s, its death count was also in the low hundreds. Then, starting in 2016, it began spiking, and is now at almost 2,000 deaths per year.

Both drugs can also be cut with other, relatively less potent opioids for a cheaper but stronger high. And both can themselves become more potent over time. Thus, the danger of synthetic opioids like ISO should not be underestimated.

And ISO isn’t just being found in just opioids, either – USA Today reported in 2020 that people dying of cocaine overdoses in Illinois and Indiana were found to also have ISO in their system. This is a versatile drug that can show up in any number of substances, including prescription medication.

Finally, ISO is likely not the last synthetic opioid we’ll see. Drug dealers are constantly refining their techniques, coming up with new drugs by slightly tweaking the chemical structure of old ones to avoid detection. Unfortunately, authorities have little way of predicting what will be the next “new fentanyl,” meaning they will continue having to play catch-up with criminals.