Entry and Availability of Nitazenes in the Unregulated Drug Market

"During the 1950s, nitazenes were developed by commercial pharmaceutical companies as synthetic opioid candidates and they were described in medical and pharmaceutical literature of the era. Thus, clandestine labs needed only to turn to the historic pharmacological literature to learn about the nitazene family. The European Monitoring Center for Drugs and Drug Addiction was first notified about the presence of isotonitazene in a biological sample obtained in July 2019 [15]. Since that time, isotonitazene has been implicated in over 200 drug-related overdose deaths in Europe and North America [7], but its presence likely is under-detected because many testing facilities are not set up to test for isotonitazene, or any other nitazenes, for that matter [8].

"Metonitazene was first identified in the street drug supply during the COVID-19 pandemic (early 2020) [13]. Metonitazene has been confirmed in 20 authentic forensic autopsies with an average serum concentration level of 6.3 ± 7.5 ng/mL (median 3.8 ng/mL, range 0.5 to 33 ng/mL) and urine concentrations of 15 ± 13 ng/mL (median 11 ng/mL, range 6-46 ng/mL) [13]. In those 20 cases, metonitazene was the sole opioid found in 30% of the decedents, but metonitazene was more often used in combination with other drugs such as fentanyl, benzodiazepines, hallucinogens, and other opioids. Medical examiners listed metonitazene as the drug contributing to the death and the manner of death was determined to be accidental in all cases [13]. A 2021 analysis of unintentional drug overdose deaths that occurred in Knox County, Tennessee, United States, found that 26 of the 218 overdoses (12%) involved metonitazene combined with fentanyl [2].

"Nitazenes are available in powders, counterfeit tablets, or liquids and may be mixed with inert substances and/or combined with other drugs, such as heroin, fentanyl, and benzodiazepines [7]. Their inclusion in other drug products is not detectable by consumers and may not be disclosed to them by sellers. When the new clandestine nitazenes entered the illicit market, they were not scheduled as controlled substances. In December of 2021, the DEA temporarily put numerous nitazenes on its Schedule I [9]. Since there are few validated methods to search for these substances and little is known about the network of clandestine labs and chemists who manufacture these drugs, the geographical distribution of these drugs is not known [7]."