The record number of people who died of a drug overdose in the U.S. in 2020 — 91,799, according to the Centers for Disease Control and Prevention’s National Center for Health Statistics — is almost exactly equal to the entire population of Santa Monica, California, a seaside city in Los Angeles County. The overdose deaths were fueled primarily by powerful synthetic opioids, including fentanyl.
Overall, synthetic opioids accounted for more than 60% of all drug fatalities during the year. The age-adjusted rate of overdose deaths in 2020 jumped 31% compared to 2019, according to the CDC.
Now, a new group of synthetic drugs even more powerful than fentanyl — nitazenes — have emerged in the U.S., health authorities say. Starting in 2019, there have been reports of forensic labs detecting the presence of nitazenes in the Southwest, South, Midwest and in some sections of the East.
[READ: 10 Signs of Addiction.]
What Are Nitazenes?
Opioids are a broad class of medications, some of which are found naturally in the opium poppy plant, some of which are manufactured synthetically. For example, prescription opioids — such as oxycodone — are often used as pain relievers; opium is used to manufacture the street drug heroin; physicians at times use the synthetic drug fentanyl to treat pain.
Many prescription opioids are used to treat moderate to severe pain. They work by blocking pain signals between the brain and the body. Opioids can also induce feelings of well-being, relaxation and being high. These feelings can lead to substance misuse and dependency.
Nitazenes are a specific subclass of opioids that work on a particular opioid receptor, says Jamie K. Alan, an associate professor in the department of pharmacology and toxicology at Michigan State University in East Lansing, Michigan.
Opioids work by attaching themselves to opioid receptors on nerve cells, which are located in the brain, spinal cord, gut and other parts of the body, according to the American Society of Anesthesiologists. Once they are attached, the opioids “block pain messages sent from the body through the spinal cord to the brain,” according to the ASA.
Researchers working for a pharmaceutical company who were developing medications for pain as an alternative to morphine originally developed nitazenes from synthetic compounds about 60 years ago, but abandoned them because they had a high potential for overdose, Alan says.
Some types of nitazenes include:
No Legitimate Medical Use
Researchers who developed nitazenes obtained a patent, but nitazenes have never been approved for use by the Food and Drug Administration.
Nitazenes are not used for legitimate medicinal purpose, says Thomas So, senior manager of the Consumer Drug Information Group at FDB (First Databank), which for 40 years has, according to the company, provided drug databases used by the majority of hospitals, physician practices, pharmacies and insurance payers in the U.S.
The Drug Enforcement Administration classifies the 10 currently known nitazenes as Schedule 1 drugs, says Alex J. Krotulski, associate director of the Center for Forensic Science Research & Education in Willow Grove, Pennsylvania. These are drugs for which there is no currently accepted medical use and a high potential for abuse.
Other Schedule 1 drugs include:
The Dangers of Nitazenes
Some forms of nitazenes are 800 times more potent than morphine and 40 times more potent than fentanyl, Krotulski says. Most known nitazenes are less potent than carfentanil, an opioid used in veterinary medicine that’s far more potent than fentanyl.
There’s no standardized or centralized mechanism for tracking deaths from nitazenes or any other new synthetic drugs in the U.S., which makes it difficult to say how many overdose deaths are associated with these drugs, Krotulski says. Based on the 600 or so nitazene cases that researchers at the CFSRE lab and a partnering lab have analyzed, Krotulski estimates there have been between 1,000 and 2,000 deaths associated with nitazene since 2019 across the entire U.S.
Where in the U.S. Have Nitazenes Appeared?
Deaths associated with nitazenes have been reported in Indiana, Illinois, Minnesota and Wisconsin, So says.
Law enforcement authorities have seized nitazenes in the following states as well as:
— New Jersey.
— New York.
How Do People Ingest Nitazenes?
Nitazenes are most commonly available and sold in powder form, but are also available as pills or as a liquid, Krotulski says. It’s likely that many users are injecting what they believe to be heroin or fentanyl, but are ingesting a substance spiked with nitazenes, he says. In powder form, the drugs are often injected but can also be snorted.
“People are not intentionally ingesting nitazenes for the most part,” adds Dr. Ryan Marino, assistant professor of emergency medicine and psychiatry at Case Western School of Medicine in Cleveland. “People are in effect being poisoned when they’re purchasing what they believe is heroin or fentanyl.”
Is There an Effective Treatment for a Nitazene Overdose?
Naloxone, which first responders often use to revive people who have overdosed on heroin or fentanyl, should be effective in treating people suffering from a nitazene overdose, though higher doses may be needed, Marino says.
Naloxone, also known by the brand name Narcan, is a synthetic medication approved by the FDA to quickly reverse an opioid overdose. It’s an opioid antagonist, which means it binds to opioid receptors to reverse and block the effects of other opioids, according to the Substance Abuse and Mental Health Services Administration.
Naloxone is used to treat overdoses of:
The life-saving treatment can be administered a number of ways, including:
— By intranasal spray.
— Injection into the muscle.
— Intravenous injection.
— Injection under the skin.
More research is needed to determine how effective naloxone is in treating nitazene overdoses, Marino says.
Krotulski adds that there is no evidence of naloxone-resistant new synthetic opioids. “The question is always administration, dose and re-dosing the naloxone.”
Are Nitazenes Overtaking Other Opioids?
It doesn’t appear that nitazenes or any other synthetic opioid will replace fentanyl’s ubiquity in the U.S., at least not in the near future, Krotulski says. However, nitazenes have displaced carfentanil and other fentanyl analogue usage. “So while nitazenes are second behind fentanyl among synthetic opioids, they lag far behind the sheer volume of fentanyl in the U.S. right now,” he says.
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Update 05/26/22: This story was previously published at an earlier date and has been updated with new information.