A relatively novel drug potentially 40 times as powerful as fentanyl has emerged as a serious public health threat according to Dr. Gregory McDonald, dean of PCOM’s School of Health Sciences and director of the MS in Forensic Medicine Program.
The drug—nitazene—was developed in the 1950s, but never approved for human use and was never marketed or manufactured for human use, McDonald said. The “recipe” for the drug could be found in academic journals, he explained, but for decades it basically “sat on the shelf”, all but forgotten. That is until recently.
“The illicit manufacturers find these things. They’re not unintelligent people,” McDonald said. “They found that this is a fairly cheap, relatively easy drug to make and it’s very, very potent.”
Part of the benzimidazole opioids class of drugs, nitazenes are sometimes referred to as a “Frankenstein opioid” due to their potency, high risk for abuse and potential lethality. The fact it can be lab-produced makes it particularly attractive to criminals because they can avoid growing, processing and transporting organic substances.
McDonald, who is the chief forensic pathologist at the Montgomery County Coroner’s Office, has conducted thousands of autopsies over the course of his career. He has witnessed first-hand the deadly impact of drugs like xylazine, but only recently investigated his first death involving nitazene. The decedent had also ingested fentanyl.
While seeing a mixture of drugs in overdose cases is not uncommon, McDonald said nitazene represents an alarming escalation of drug potency.
“Fentanyl is more potent than morphine. Morphine is more potent than heroin and then you have this drug that can potentially be more potent than fentanyl,” he explained.
The potency, he added, varies according to which analogue, or variant, of nitazene is used.
“There’s no uniformity,” McDonald said. “You don’t know how potent it is when you’re buying something on the street. You don’t know what you’re getting.”
Like other synthetic opioids including fentanyl, nitazene can cause life-threatening respiratory depression. The more potent analogues may produce effects that cannot be reversed by naloxone (NARCAN®).
The lack of uniformity also presents a problem from a law enforcement perspective. To be categorized by the Drug Enforcement Administration (DEA) as a scheduled drug—a controlled substance that is illegal—you must be able to define the structure of the drug.
According to a January 2024 memo from the Drug and Chemical Evaluation Section of the DEA’s Diversion Control Division, there are 10 forms of nitazenes listed as Schedule I controlled substances. Drug manufacturers can attempt to circumvent this categorization by continuing to develop analogues that are similar in chemical structure to the controlled substance yet different enough to not meet the definition of the scheduled drug.
“From a law enforcement perspective, this can certainly make it challenging to keep up with these labs and be able to ultimately convict (the manufacturers) and shut them down,” McDonald said.
Autopsy findings may indicate a death was likely caused by opioid use, but a toxicology workup is necessary to confirm the presence of nitazene.
“I would not sign a case out until I had that final toxicology report,” McDonald emphasized.
McDonald concedes the number of nitazene deaths is likely larger than the handful of confirmed cases reported in the Philadelphia area to date. Initially, the toxicology labs did not know how to test for it.
“That’s always a challenge—keeping ahead of the pharmacology to be able to test for it,” he said. “So my guess is that this is the tip of the iceberg.”
As a professor in PCOM’s MS in Forensic Medicine program, McDonald is already working to ensure graduates of the program understand the challenges of investigating these types of deaths.
“I talk about the mechanism of action of opioids and the specific type of opioids they are likely to see on the streets,” he said. “I just added this to the lecture because it’s a relatively novel phenomenon.”
His goal, he said, is to make sure his students have a basic understanding of this class of drugs and current trends. He wants them to be prepared should they have to review a toxicology report with findings related to nitazene. He also hopes to convey the threat to public health these drugs pose.
In the process of updating his lecture, McDonald came across an article with a quote he described as “a bit telling and a bit ominous.”
“It said more Americans are dying of opioid overdoses than at any other time in American history,” McDonald recalled. “I totally believe that.”
While the whole opioid crisis is bad, he said, the constant addition of new drugs makes it difficult to keep up in terms of testing for the drugs, treating users and keeping laws up to date.
“It can be a real challenge,” McDonald said. “Add to that the way nitazene is relatively easy and cheap to make—and very potent—those are all really bad combinations for public health.”
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