{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T18:05:20Z","timestamp":1775757920531,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}]},{"name":"FCT","award":["UIDP\/00100\/2020"],"award-info":[{"award-number":["UIDP\/00100\/2020"]}]},{"name":"FCT","award":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}]},{"name":"FCT","award":["10.54499\/UIDB\/04585\/2020"],"award-info":[{"award-number":["10.54499\/UIDB\/04585\/2020"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Molecules"],"abstract":"<jats:p>The global unregulated drug supply faces a critical challenge with the emergence of nitazenes, a class of novel synthetic opioids (NSOs) structurally distinct from fentanyl and associated with extreme potency and high risk of fatal overdose. First synthesised in the late 1950s, etonitazene was a target of preclinical research in rats and rhesus monkeys, but it never reached clinical trials due to an unfavourable balance between therapeutic and toxic effects. Nitazenes\u2019 consistent reappearance began in 2019 with isotonitazene, followed by a rapid proliferation of analogues worldwide, many reported to be hundreds to thousands of times more potent than morphine and, in some cases, stronger than fentanyl. This rise is fuelled by their ease of synthesis, low production costs, and evasion of regulatory controls. Nitazenes are frequently mis-sold as counterfeit medications or adulterated into other drugs, resulting in unintentional exposure and overdose, particularly among opioid-na\u00efve users. The primary cause of death is severe and prolonged respiratory depression. Analytical challenges are significant, as traditional screening methods are ineffective, and the low concentration in biological samples requires expensive and highly sensitive liquid chromatography mass spectrometry techniques. This perspective paper highlights critical gaps in detection, clinical management, and regulatory readiness for nitazenes. Urgent efforts are needed to improve surveillance, develop robust analytical methodologies, provide clinical guidance to nitazene intoxications, and strengthen international policy to curb their proliferation.<\/jats:p>","DOI":"10.3390\/molecules30193890","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:31:28Z","timestamp":1758875488000},"page":"3890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nitazenes: The Emergence of a Potent Synthetic Opioid Threat"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2994-3379","authenticated-orcid":false,"given":"Joana R. P.","family":"Pereira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Ci\u00eancias Forenses e Psicol\u00f3gicas Egas Moniz, Quinta da Granja, 2829-511 Caparica, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5188-0453","authenticated-orcid":false,"given":"Alexandre","family":"Quintas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ci\u00eancias Forenses e Psicol\u00f3gicas Egas Moniz, Quinta da Granja, 2829-511 Caparica, Portugal"},{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health & Science, Quinta da Granja, 2829-511 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-1565","authenticated-orcid":false,"given":"Nuno R.","family":"Neng","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Ci\u00eancias Forenses e Psicol\u00f3gicas Egas Moniz, Quinta da Granja, 2829-511 Caparica, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisbon, Portugal"},{"name":"Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health & Science, Quinta da Granja, 2829-511 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref_1","unstructured":"United Nations Office on Drugs and Crime (2025, August 22). 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