New monster opioids make fentanyl look tame

Last month, authorities in Santa Clarita, Calif., charged a 21-year-old man with distributing protonitazene, a kind of super-opioid, resulting in a death. It’s believed to be the first fatal criminal case in the United States involving the drug. The alleged victim, a 22-year-old man, was found dead in his car by his mother after he ingested protonitazene purchased from the Santa Clarita man, according to the U.S. attorney’s office in the central California district.

Protonitazene belongs to a group of synthetic opioids also known as nitazenes that are believed to be several times more powerful than the deadly synthetic opioid fentanyl. But the case sparked little media attention.

Robert Pennal, a retired supervisor with the California Department of Justice’s Bureau of Narcotic Enforcement said the drugs’ obscurity isn’t surprising. “Most … police officers, they have no idea what [a] nitazene is,” he said. And that worries him.

Scientists developed nitazenes during the 1950s, around the time Belgian physician Dr. Paul Janssen synthesized fentanyl. The researchers tinkered with the formula in hopes of creating an opioid with a chemical structure significantly different from morphine to use in managing pain. But it soon became clear the adverse effects and potential for abuse and overdose overwhelmed any beneficial analgesic effect. The drugs were never approved for therapeutic use.

Covert chemists operating underground labs sifted through historical research documenting these early attempts at creating synthetic opioids. “The recipes or synthesis methods are available now in an internet era, and illegal chemists have access to these,” said Jonathan Caulkins, a drug policy researcher and Carnegie Mellon University professor. “They’re very, very cheap to make, and they can be made anywhere.”

Pennal believes it won’t be long before nitazene becomes as ubiquitous as fentanyl. “That’s the next generation of opiates,” he said. The latest Centers for Disease Control and Prevention data show that, overall, fatal drug overdoses in the United States fell almost 17% between July 2023 and July 2024. But in a recent report, the agency warned that synthetic opioids such as nitazenes and fentanyl analogs—opioids in the fentanyl family with a slightly modified chemical structure— could reverse that trend.

Pennal said law enforcement officers aren’t seizing kilograms of nitazenes—yet. But they are finding them in small batches of pills here and there, he told me, as dealers slowly build their sources. Fentanyl distribution followed the same pattern.

In 2014 and 2015, Chinese manufacturers began advertising fentanyl online to North American dealers as a cheap and potent alternative to heroin. It started showing up in illicit prescription pills and had thoroughly infiltrated the street supply by the time the COVID-19 pandemic forced everyone inside—alone with their drug habits. By 2022, total overdose deaths had jumped to 107,941,more people than could fit in the nation’s largest football stadium.

Nitazenes range from slightly less potent than fentanyl to up to 43 times stronger, according to a September 2024 Inter-American Drug Abuse Control Commission report. They’re typically sold as a white or brownish-yellow powder, and have also been identified in pills or mixed with other drugs. Like many first-time fentanyl users, most opioid addicts aren’t aware they’re consuming the drugs.

“If it was a nitazene pill and you thought it was a fentanyl pill, you couldn’t tell the difference,” Pennal said. “Then all of a sudden, you go into respiratory arrest.” Instead of one or two doses of Narcan—the nasal spray version of the anti-overdose drug naloxone—the user would probably need three or four doses, he said. That is, if he or she woke up at all.

Isotonitazene, known as ISO on the streets, is one of the most common nitazenes. It’s more potent than protonitazene and could be up to 20 times stronger than fentanyl. Earlier this year, law enforcement identified the drug in Merced County, Calif., during an undercover operation known as Operation Red Rooster, Pennal said. Undercover agents tracked Honduran traffickers peddling the synthetic opioid, according to Pennal, and he said that intercepted texts show the dealers warned their customer about the drug’s potency.

Despite the danger, Pennal said the novelty of a new, stronger drug appeals to users. “If you say you have something that’s more powerful, [obscenity] they want that,” he said.

As of January 2024, the Drug Enforcement Administration had catalogued 20 different kinds of nitazenes. In a fact sheet released that same month, the agency identified nitazenes as an “emerging threat” and warned the drugs are popping up in samples of fentanyl, heroin, and cocaine.

Europe is reckoning with the growing threat of synthetic opioids, including nitazenes, as the Taliban’s crackdown on the opium trade in Afghanistan squeezes the heroin pipeline. Australian authorities warn that nitazenes have also infiltrated their country’s drug supply. In Sydney, a warning blasted over the loudspeakers brought a music festival to a halt after two people overdosed on pink MDMA pills laced with a nitazene.

Deaths linked to fentanyl analogs are also on the rise, the CDC reported earlier this month. Drugs cut with carfentanil, one of the most potent fentanyl derivatives discovered so far, killed 513 people in the United States between January 2021 and June 2024, and over half of those deaths took place this year. The odorless white powder is used to tranquilize large animals and is 100 times more potent than fentanyl. A 2 milligram dose of the drug—about what fits on the tip of a pencil—can prostrate an average-sized elephant and kill 50 people.

The reason potent synthetic opioids like carfentanil are so dangerous is that it’s “hard to precisely dilute a powder, especially when the proportion of the active ingredient is so small,” Caulkins said. Dealers inadvertently sell some bags that have a higher dose of the drug than others.

Carfentanil has been found in benzodiazepines like Xanax and is often cut with heroin to intensify the high, said Dr. Chris Tuell, clinical director of addiction services at the Lindner Center of HOPE and an assistant professor of clinical psychiatry at the University of Cincinnati College of Medicine. He believes few people seek out the monster opioid, but users inevitably risk exposure when they purchase drugs off the street. The danger of contamination often doesn’t register with a user’s addiction-addled brain, he said.

Hawre Jalal, an associate professor at the University of Ottawa’s school of epidemiology and public health, said deaths caused by fentanyl analogs are likely “severely undercounted” since most coroners and medical examiners lack the equipment to detect the analogs and other novel synthetic opioids in toxicology screenings.

Jalal co-authored research investigating a spike in carfentanil deaths between 2016 and 2017 in five states—Michigan, Florida, Pennsylvania, Kentucky, and especially Ohio. Carfentanil was a factor in 191 fatal overdoses in Cuyahoga County, Ohio, in 2017, the medical examiner’s report shows.

Both Jalal and Caulkins told WORLD that data about the nitazene and fentanyl analog supply chain is limited. A 2021 U.S. Sentencing Commission report noted that while fentanyl was more likely to enter the United States through the U.S.-Mexico border, dealers sentenced for distributing fentanyl analogs more often purchased their supplies on the dark web, frequently from China.

But unauthorized chemists tweak illegal compounds to evade regulations, Jalal said. The DEA’s National Forensic Laboratory Information System has catalogued 118 distinct fentanyls and fentanyl-related substances.

After the spate of deaths in 2016 and 2017, carfentanil largely disappeared for several years. Caulkins with Carnegie Mellon University said it isn’t clear why the fentanyl analog is cropping up again, or why some communities suddenly become hotspots for other synthetic opioids like nitazenes. A supplier may decide to experiment with a specific market, what Caulkins described as “testing the waters,” to see how users respond to a new, more potent product.

Some experts believe the overall decline in fatal overdoses, in part, reflects the efforts of the U.S. and Chinese governments to restrict the fentanyl precursor industry. But even if the two countries successfully curtail precursor production, it’s unlikely the market will ever move away from synthetic opioids, Caulkins said. “They could switch classes, say, to the nitazenes,” he added.

Pennal, the law enforcement consultant in California, believes that’s already happening.

“It’s here,” he said. “They have their supply and they have their trafficking routes all in place.” Still, he added, it could be a few more years before nitazenes infiltrate the illicit drug supply to the same degree as fentanyl.

Controlling the illicit drug supply isn’t enough to stall the deadly progression toward even more lethal drugs, Jalal at the University of Ottawa argued. The opioid epidemic didn’t start with fentanyl and it won’t end with nitazenes, and hyperfixating on the newest, novel drug won’t solve America’s insatiable appetite for mind-altering substances.

“There’s the demand side to it, and there’s also the supply side to it,” Jalal said. “And I think we need to understand both.”