Navigating nitazenes: A pharmacological and toxicological overview of new synthetic opioids with a 2-benzylbenzimidazole core

Abstract

Since the first identification of isotonitazene on the recreational drug market in 2019, new synthetic opioids (NSOs) with a 2-benzylbenzimidazole core (colloquially known as ‘nitazene’ opioids) have increased in prevalence. At the end of 2024, 22 different analogues had been identified in Europe, and worrying trends indicate their increasing presence at the street level. Nitazene analogues originate from a series of research articles from the 1950–60s, but were never marketed as analgesics. Recent pharmacological research has shown that different analogues are highly active, with several being more potent than fentanyl in their ability to activate the μ-opioid receptor and produce opioid effects. This high potency, combined with their unpredictability on the recreational drug market, legal status in some regions, and economic appeal to drug producers, has contributed to a growing number of intoxications and fatalities involving nitazene analogues worldwide. This literature review focuses on the pharmaco-toxicology of nitazene opioids and the characteristics of their emergence on the NSO and broader recreational drug markets from 2019 onwards. Aspects that are covered include (a) a systematic approach to the naming of nitazene analogues, (b) trends, prevalence and identifications on the recreational drug market, (c) structure-activity relationships derived from recent in vitro, in vivo, and in silico research, (d) strategies for detection in biological samples and drug material, and (e) the current legal framework. Finally, innovative approaches to navigate this complex landscape are discussed, together with an outlook for the future.