Growth of Nitazenes on the Unregulated Market Predicted in 1975

"Following the core scheduling of fentanyl analogues (first temporarily in 2018 and then permanently in 2023), the illicit recreational drug market started switching to alternatives that were not registered as Schedule I Substances [12]. Interestingly, researchers predicted the misuse of nitazenes as early as 1975 due to the relatively easy manufacturing process and extreme potency [13]. According to the United Nations Office on Drugs and Crime (UNODC), the number of nitazene analogues is now quickly rising, with the European Union Drugs Agency (EUDA) now monitoring 81 new opioids, 16 of which are nitazenes [14, 15]. As of 2024, the UNODC has listed a total of seven of these nitazenes as Schedule I Substances: etonitazene and clonitazene (added in 1961) and butonitazene, protonitazene, etonitazepyne, metonitazene and isotonitazene (all five added between 2021 and 2024) [16]. These last five nitazenes were added in recent years due to the sudden increase in sales and usage of these substances, mostly in North America (United States and Canada), Australia and Europe (United Kingdom, Slovenia, Estonia, Latvia, Belgium and the Netherlands) [14, 17].

"Due to the potency of nitazenes in combination with often unknowing buyers and users of the substances, the UNODC, the World Health Organization (WHO) and the EUDA have warned and alerted agencies and health professionals of the emergence of these substances [14, 17, 18, 19]. The UNODC reports that synthetic opioids account for the largest burden of disease attributed to drug use disorders, as the high potency of these substances, including fentanyl and nitazenes, can cause overdoses with only minimal quantities of drug ingested [14]."