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Early identification of the use of potent benzylbenzimidazoles (nitazenes) through wastewater analysis: Two years of data from 22 countries

  • Richard Bade
  • , Dhayaalini Nadarajan
  • , Wayne Hall
  • , Nicola Ceolotto
  • , Jared A. Brown
  • , NPS Consortium
  • , Jennifer Schumann
  • Universitat Jaume I
  • University of South Australia
  • University of Queensland
  • Toxicity Response, Epidemiology and Surveillance, Centre for Alcohol and Other Drugs, NSW Ministry of Health, St Leonards, Australia
  • University of Sydney
  • Victorian Institute of Forensic Medicine, Southbank, Australia
  • Department of Forensic Medicine, Monash University, Southbank, Australia
  • Monash Addiction Research Centre, Frankston, Australia

Research output: Contribution to journal › Article › peer-review

21   Link opens in a new tab Citations (SciVal)

Abstract

Background and Aims
The use of new synthetic opioids, such as the highly potent 2-benzylbenzimidazoles (i.e. nitazene) drugs, is a global health concern because of their increased risk of fatal overdose. In the early 2020s, nitazene analogues were linked to significant numbers of overdoses in the United States. Their reach is now worldwide, with nitazene overdose deaths reported in Europe, Australia and New Zealand. The aim of this study was to measure quantities of nitazenes in wastewater samples collected from 68 locations in 22 countries, covering six continents, to understand and estimate their use.

Methods
Untreated influent wastewater samples were collected over a one-week period that included the New Year period in 2022–2023 and 2023–2024. Samples were collected from 22 countries: Australia, Austria, Belgium, Brazil, Canada, Chile, China, Cyprus, Czechia, France, Germany, Greece, Iceland, Italy, New Zealand, Nigeria, Republic of Korea, Slovenia, Spain, Sweden, United Kingdom and United States. Samples were loaded onto solid-phase extraction cartridges in the country of collection and sent to Australia for elution and analysis using sensitive liquid chromatography–mass spectrometry methods.

Results
A total of 683 individual wastewater samples were analysed across the two years: 339 in 2022–2023 and 344 in 2023–2024. Two nitazene analogues—protonitazene and N-pyrrolidino etonitazene (etonitazepyne)—were found in five separate sites in the United States and Australia. In the 2022–2023 period, protonitazene was found in two sites in the United States. The following year, protonitazene was detected in two further sites in the United States, while both protonitazene and etonitazepyne were found in one site in Australia. Protonitazene mass loads ranged between 0.3 mg/day/1000 people and 100 mg/day/1000 people. Etonitazepyne was also found at mass loads between 0.2–2 mg/day/1000 people).

Conclusions
A very high mass load of protonitazene was calculated, using wastewater analysis, for the day of 30 December 2023 in one site in Australia. Etonitazepyne showed the same trend from a lower base. Wastewater-based nitazene surveillance shows promise as a form of both drug early warning and ongoing monitoring of trends in use, especially as a complementary tool to existing surveillance methods.
Original languageEnglish
Pages (from-to)1739-1746
Number of pages8
JournalAddiction
Volume120
Early online date18 Mar 2025
DOIs
Publication statusPublished - 4 Aug 2025

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgements

We sincerely thank the wastewater treatment plant operators for their help in collecting samples and the support provided by the lab staff who performed the extraction of the samples. We also thank SCIEX for the use of their instrument. The Queensland Alliance for Environmental Health Sciences, The University of Queensland, grate-fully acknowledges the financial support of Queensland Health, Australia. The National Centre for Youth Substance Use Research receives funding from the Commonwealth Department of Health. R.B. is the recipient of an Australian Research Council Discovery Early Career Award (project number DE220100381) funded by the Australian Government. The views expressed in this article are those of the author(s) and not necessarily those of the funding agencies. Open access publishing facilitated by The University of Queensland, as part of the Wiley - The University of Queensland agreement via the Council of Australian University Librarians.

Keywords

  • early warning system
  • etonitazepyne
  • illicit drugs
  • new psychoactive substances
  • protonitazene
  • wastewater-based epidemiology

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