1950s–1970s: Original development and abandonment
- Mid–late 1950s – Swiss company CIBA AG (now part of Novartis) synthesises etonitazene and related 2‑benzylbenzimidazole opioids (later called nitazenes) as potential analgesics.
- 1957–1960s – Early pharmacology papers show extremely high potency (hundreds to thousands of times more potent than morphine); clinical trials reveal severe respiratory depression and very low therapeutic index.
- Outcome – Nitazenes are never approved or marketed, and remain a largely forgotten “failed opioid” class, known mainly in specialist literature.
1980s–2000s: Isolated illicit appearances
- Late 1960s–1990s – Etonitazene/etodesnitazene appear sporadically in Italy, Germany, Russia as rare street opioids, but do not create a sustained market.
- 1998 – 10 nitazene‑linked deaths reported in Moscow—one of the first documented illicit clusters.
- 2003 – A single case of personal nitazene synthesis reported in Utah, USA.
- These remain exceptions, not the start of the current global wave.
2010s: Fentanyl bans and “rediscovery”
- 2010s – North America’s opioid crisis shifts from prescription opioids to heroin, then to illicit fentanyl and analogues.
- 2019 (China) – China introduces a class-wide ban on fentanyl analogues, making production/export of fentanyls riskier.
- Clandestine chemists begin mining old literature for non‑fentanyl synthetic opioids; nitazenes are “rediscovered” as a high-potency, non‑fentanyl option.
2019–2020: Modern emergence of nitazenes
- July 2019 (Europe) – EMCDDA receives the first notification of isotonitazene in a biological sample, marking its entry into the modern illicit market.
- 2019 (UNODC) – Isotonitazene is first reported to the UNODC Early Warning Advisory; by 2020–2021, multiple new nitazenes are identified.
- 2019–2021 (Canada/US) – Canada records 615 nitazene/brorphine detections (2019–2021), with isotonitazene initially dominant and protonitazene emerging from late 2020.
2020–2022: Global spread
- By 2022 – Nitazenes have been reported in at least 19 countries, including the US, Canada, UK, Latvia, Estonia, Sweden, Germany, and others.
- 2020–2022 – Early deaths and outbreaks involve isotonitazene, metonitazene, and etonitazene, often in counterfeit tablets and adulterated heroin.
2022: Taliban opium ban and the European vulnerability
- April 2022 – Taliban ban opium poppy cultivation; Afghan cultivation collapses by about 95%.
- Afghanistan had supplied ~95% of UK heroin, so this creates a looming supply shock for Europe and the UK.
- As heroin purity drops and prices rise, conditions become favourable for synthetic opioids, including nitazenes, to fill the gap.
2022–2023: UK and Europe begin to see impact
- 2022 – First sustained nitazene detections in the UK and across Europe; isotonitazene and metonitazene appear in heroin and counterfeit pills.
- May 2022 – First known UK xylazine death (often in mixtures with nitazenes), showing the broader trend of complex synthetic adulteration.
- 2023 (UK) – Clusters of deaths in Birmingham/West Midlands when nitazenes are used to “fortify” low‑purity heroin.
2023–2024: Shift towards protonitazene and wider harms
- 2023–2024 – Protonitazene increasingly dominates nitazene detections and deaths in several countries (Canada, UK, parts of Europe).
- June 2023–May 2024 (UK) – 284 deaths linked to nitazenes; protonitazene is the single most common analoguein English deaths, followed by N‑desethyl‑isotonitazene and metonitazene.
- Public health reviews describe nitazenes as “old drugs causing new problems” and warn of their potency, presence in heroin and fake pills, and need for multiple naloxone doses.
2023–2024: Online marketing and Chinese supply
- 2023–2024 – BBC and other investigations expose Chinese suppliers openly advertising nitazenes on SoundCloud and X, shipping powders to the UK disguised as dog food or other goods, with payments via cryptocurrency.
- Texts seized from UK dealers show they were initially reluctant to use nitazenes but were persuaded by Chinese suppliers.
- Nitazenes become a key adulterant in heroin, benzodiazepines, and counterfeit opioid pills across the UK and Baltic states.
2023–2025: Regulation tightens
- Pre‑2024 (UK) – Only etonitazene and clonitazene are explicitly Class A; many newer nitazenes remain unscheduled.
- March 2024 (UK) – Fifteen synthetic opioids (including key nitazenes) made Class A; generic provisions expanded later to cover the whole class.
- 2024–2025 (EU/US) – Multiple nitazenes placed under international control or scheduled nationally; agencies issue alerts on isotonitazene, metonitazene, protonitazene, N‑pyrrolidino‑protonitazene, etc.
2025: China and full class control
- June 2025 (China) – China announces that all nitazenes and 12 other NPS are brought under narcotic control.
- UNODC and European agencies predict this will shift the market rather than end it, likely pushing synthesis towards new nitazenes or entirely different opioid families.
2024–2025: Current global picture
- By early 2024, UNODC has records for 13+ distinct nitazenes reported from Asia, Europe, North America, Oceania, and South America, with 26 named by 2025.
- The World Drug Report 2025 shows nitazenes now present in dozens of countries, with protonitazene the most frequently identified analogue globally and particularly prominent in the UK and Baltic region.
- Reviews in 2024–2025 conclude nitazenes are likely to remain part of the illicit opioid market for the indefinite future, especially as suppliers respond to controls by tweaking chemistry.