Clin Toxicol (Phila). 2026 Feb 8:1-13. doi: 10.1080/15563650.2025.2601141. Online ahead of print.
ABSTRACT
INTRODUCTION: Nitazenes are potent synthetic opioids. Following reports questioning their post-mortem stability, nitazene-related deaths may have been underestimated in the United Kingdom. We investigated this using a rat model and regional coronial data, and also present national pharmacoepidemiologic trends in nitazene-related deaths.
METHOD: In vivo/ex vivo study: Anaesthetised Wistar rats (n = 12) received intravenous nitazene (metonitazene, N-desethyl isotonitazene, or N-pyrrolidino etonitazene). Rats were euthanised 15 min post-administration if cardiorespiratory arrest had not already occurred (n = 8). Blood and urine were collected, with repeat blood samples taken following cadaver refrigeration (4 °C) for one week. All samples were immediately frozen (-80 °C). Upon defrosting, half were analysed immediately by liquid chromatography tandem mass spectroscopy with half stored at 4 °C for 1 month before analysis.
PHARMACOEPIDEMIOLOGY: Nitazene deaths were extracted from the National Programme on Substance Use Mortality in March 2025 along with all deaths from the Birmingham & Solihull coronial area (2019-2023). Descriptive analyses were conducted along with exponential smoothing models to compare observed and forecasted deaths in Birmingham & Solihull in 2023.
RESULTS: In vivo/ex vivo study: A small fraction of the nitazene detected in the immediate post-mortem blood sample remained in the post-mortem day 7 blood sample that had been refrigerated for 1 month.
PHARMACOEPIDEMIOLOGY: In Birmingham and Solihull, non-nitazene drug deaths rose 33% in 2023 compared to 2019-2022 (predicted n = 107, actual n = 142). By March 2025, 285 deaths with nitazene detections were reported to the National Programme on Substance Use Mortality, with small clusters in 2021 (n = 23) and 2022 (n = 15) before markedly increasing in 2023 (n = 131). Twelve nitazenes were detected with the predominant nitazene shifting over time (2021: isotonitazene; 2022: N-pyrrolidino etonitazene; 2023: N-desethyl isotonitazene). Coroners deemed nitazenes causative in 90% of cases (n = 256/285).
CONCLUSIONS: Nitazene-related deaths have increased in England, Wales, and Northern Ireland, and may have been underestimated due to post-mortem instability. Urgent public health action is required to reduce nitazene-related harms.
PMID:41655595 | DOI:10.1080/15563650.2025.2601141
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