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February 2026 - Increasing nitazene and orphine analogues (synthetic opioids) and the implications for the use of test strips

VIENNA, Austria – 25 February 2026: Nitazenes are a class of potent synthetic opioids comprising multiple structural analogues. The earliest reported analogue of this group, isotonitazene, was notified to the UNODC Early Warning Advisory in 2019. Since then, a total of 34 analogues have been notified to UNODC and they have increasingly been detected in seized drug samples and toxicology casework across at least 37 countries (Figure 1).

Figure 1: Emerging nitazene and orphine analogues reported to the UNODC EWA since 2013 (pre-2013 is reporting the year of international control).

Source: United Nations, UNODC Early Warning Advisory on New Psychoactive Substances (EWA), Database (accessed on 17 February 2026).
Note: Clonitazene, etonitazene and bezitramide (orphine analogue) have been under international control since 1961 and 1969, respectively. Since the launch of the UNODC EWA, 34 nitazenes and 10 orphine analogues were reported to UNODC. The years shown in black indicate the first year each substance was reported to the UNDOC EWA. Data collection for 2025 is ongoing.
*These substances are under international control (Single Convention on Narcotic Drugs of 1961/Schedule I). Their chemical names are listed as the names under which they are included in the International Drug Control Conventions.
**These nitazenes were reviewed at the 48th WHO Expert Committee on Drug Dependence (ECDD) meeting in October 2025 and recommended for scheduling (to be added to the Single Convention on Narcotic Drugs of 1961/Schedule I). The chemical names are listed as in  Annex 1: 48th WHO ECDD summary assessments and recommendations.


In response to rising concerns surrounding the increased prevalence of nitazenes in the illicit market; the use of immunoassay testing strips as a harm reduction method in drug checking services and the community has become increasingly common, particularly in countries across Europe, Oceania and North America.

However, research has highlighted limitations in the accuracy of these test strips for the detection of nitazene analogues in street samples. Immunoassay test strips are developed to detect a limited subset of nitazenes, often isotonitazene and/or protonitazene. Due to the structurally diverse nature of nitazenes, this does not ensure cross-reactivity with all analogues, meaning a negative result does not reliably indicate the absence of all nitazene-type opioids. Research has shown that in particular ‘desnitazene’ analogues, such as etodesnitazene (etazene), are often not detected by the test strips [1-4]. Furthermore, substantial variability in limits of detection across different analogues further limits the reliability of these tests for the comprehensive detection of structurally diverse nitazenes [1,2,4]. As the range of nitazene analogues continues to expand, so too does the likelihood that testing strips will fail to detect newer or structurally distinct analogues.

In addition, some commercially available test strips [1] have demonstrated issues relating to cross reactivity with caffeine at higher concentrations, a common adulterant in heroin. As a result, it is common for these test strips to produce a false positive result when testing street samples of heroin.

The situation is further complicated by the rising detection of orphine analogues, often referred to as “orphines” - another class of synthetic opioids that are structurally distinct from both fentanyl and nitazenes. Orphines are not detected by nitazene nor fentanyl test strips [5]. Brorphine was first reported in 2019 and internationally controlled in 2022.[6] Eleven orphine analogues have now been reported to UNODC Early Warning Advisory by 14 countries, with nine of these analogues being reported in 2024 and 2025 (Figure 1). A new structural group for orphine analogues has now been incorporated into the UNODC Early Warning Advisory. Data from North America highlights increased detections of orphines, in particular, N-propionitrile chlorphine (cychlorphine) in drug seizures and fatal overdoses [7-8]. As these compounds appear more frequently in the drug supply, reliance on immunoassay test strips may leave critical gaps in risk detection.

Although immunoassay test strips have been demonstrated as valuable engagement tools [9], caution needs to be taken when being deployed in harm reduction settings. Due to variability between national drug markets recommendations for use should be developed locally and their limitations carefully communicated before use in these settings. The UNODC Early Warning Advisory allows registered users to stay up to date on emerging trends through a variety of visualisations and search options.

 

***This Early Warning Advisory message was produced in collaboration with Victoria Marland from the Leverhulme Research Centre for Forensic Science, University of Dundee.

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[1] Marland and others, “Evaluation of nitazene immunoassay test strips for rapid in-situ detection of nitazene and nitazene analogs in illicit drug samples”, Harm Reduction Journal, vol. 22, No. 137 (August 2025).

[2] De Vrieze and others, “Nitazene test strips: a laboratory evaluation”, Harm Reduction Journal, vol. 21 (August 2024).

[3] Ontario’s Drug Checking Community, “Performance assessment: Nitazene test strips”. Available at: https://drugchecking.community/wp-content/uploads/dlm_uploads/2026/01/Nitazene-test-strip-performance-assessment-v1_ODCC.pdf (accessed on 18 February 2026).

[4] Johnson, O. and others, “Trial for BTNX Rapid Response Nitazene Test Strips”, Drug Checking Technical Report (April 2024). Available at: https://research.esr.cri.nz/articles/report/Trial_for_BTNX_Rapid_Response_Nitazene_Test_Strips_-_Part_One/27616896?file=50240436 (accessed on 20 February 2026).

[5] Norman and others, “Evaluation of fentanyl immunoassay test strips for rapid in-situ detection of fentanyl and fentanyl analogs in seized samples and alternative matrices”, International Journal of Drug Policy, vol. 118 (August 2023).

[6] United Nations, “Orphine analogues”, UNODC Early Warning Advisory on New Psychoactive Substances Database. Available at: https://unodc.org/LSS/SubstanceGroup/Details/09f4734d-aadb-44a0-aa76-2e8816b1cc02 (accessed on 20 February 2026).

[7] Krotulski and others, “Increase in Fatal Overdoses Linked to Novel Synthetic Opioid N-Propionitrile Chlorphine (Cychlorphine)”, Center for Forensic Science Research and Education (2026). Available at: https://cfsre.org/nps-discovery/public-alerts/increase-in-fatal-overdoses-linked-to-novel-synthetic-opioid-n-propionitrile-chlorphine-cychlorphine (accessed on 18 February 2026).

[8] United States, Department of Justice, Drug Enforcement Administration, Diversion Control Division, “National Forensic Laboratory Information System”, database. Available at: https://nflis.deadiversion.usdoj.gov/ (accessed on 18 February 2026).

[9] Scottish Drugs Forum, “Just say know: living experience and staff perspectives on nitazene testing strips” (July 2025). Available at: https://sdf.org.uk/wp-content/uploads/2025/07/Just-Say-Know-Living-Experience-and-Staff-Perspectives-on-Nitazene-Testing-Strips.pdf (accessed on 18/02/2026).

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