Two deaths in Boulder County, Colorado, in 2023 are the latest in the United States attributed to a powerful class of synthetic opioids called nitazenes. Most healthcare systems cannot detect these substances, so the exact number of overdoses is unknown, but they are known to be involved in more than 200 deaths in Europe and North America since 2019, including 11 in Colorado since 2021. One of The two Boulder County deaths are related to a new formulation called N-Desethyl etonitazene, which was identified by a national laboratory, and is believed to be the first death from this compound.
The Conversation has interviewed Christopher Holstege, professor of emergency medicine and pediatrics at the University of Virginia School of Medicine and director of the Blue Ridge Poison Center, where opioid overdoses are increasing. He explains why nitazenes are so potent and deadly.
What are nitazenes?
Nitazenes are a class of synthetic opioids that encompass more than 20 unique compounds, including isotonitazene, which was first identified in 2019 and is popularly known as ISO. Also includes protonitazene, metonitazene and etonitazene.
Nitazenes are psychoactive substances or “designer drugs” that are not controlled by any law or convention, but pose a significant risk to public health. These drugs have recently appeared as illegal drugs on the streets.
Researchers have relatively little information regarding how the human body reacts to nitazenes, since they have never been subjected to clinical trials. But laboratory tests show that some of them might be hundreds or thousands of times more potent than morphine and 10 to 40 times more potent than fentanyl.
The U.S. Drug Enforcement Administration has classified many formulations of nitazenes as Schedule 1 drugs of the Controlled Substances Act, meaning they have no medical use and pose a high risk of abuse.
When were they first developed?
Nitazenes were initially developed in the 1950s by the pharmaceutical research laboratories of the Swiss chemical company CIBA. This company synthesized numerous substances of this class for use as analgesics.
However, they were never approved by the US Food and Drug Administration for medical use in humans. They were virtually forgotten outside of specialized research circles until they re-emerged as street drugs in 2019.
As law enforcement has cracked down on other drugs, such as fentanyl, illegal labs have used historic pharmacological research to formulate analogues of nitazenes as street drugs.
As of 2019, at least six formulas come from the original patent, but others, like the one detected in Boulder, are completely new. Specialized laboratory testing is required to identify nitazenes in toxicology samples. Fentanyl test strips cannot detect nitazene analogues.
Since they were first detected, these substances have been responsible for 200 drug-related overdose deaths in Europe and the United States. Although they are already identified as illegal drugs in numerous countries, many medical professionals do not even know they exist.
What types of nitazenos circulate on the streets?
Nitazene first appeared in 2019 in the US Midwest as a white, cocaine-like powder. It was later detected on the streets of Washington DC as yellow, brown and white powders. Since 2022, the DEA has found other types of nitazenes in both powder and blue pills.
Nitazenes are also mixed with other street drugs such as heroin and fentanyl and with fake oxycodone pills, without users knowing.
The US Department of Justice has accused several companies in China of sending chemical raw materials to manufacture them to Mexico and the US, where cartels and traffickers mix them and then distribute them on the streets.
What are the symptoms of an overdose?
The toxic effects of nitazene resemble those associated with other classic opioids such as morphine and fentanyl and include reduced pupils and slowing of the respiratory and central nervous systems, which can lead to death.
Because of its potency, symptoms can develop quickly following someone is exposed, causing death before they can receive medical attention.
Does naloxone counteract the effects of overdose?
Naloxone, commonly known as Narcan, is supposedly effective in reversing overdoses due to nitazene, but multiple potent doses may be necessary.
Christopher P. Holstege. Professor of Emergency Medicine and Pediatrics, University of Virginia
This article was originally published in The Conversation.
