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On 9 November 2023, the Health Service Executive Ireland (HSE) was notified of an unusually high pattern of opioid overdoses occurring in Dublin city centre among people attending homeless services. This represented the very early signs of drug market changes and the emergence of N-pyrrolidino protonitazene in Ireland. During the following 5 days there were 57 overdoses among people who use heroin in Dublin city centre, followed by a second outbreak over 6 days in the Cork region in December (n = 20) [1]. Rapid responses helped to protect people who use drugs through an urgent analytical review of samples, mobilization of frontline services to deliver tailored harm reduction measures and 'Red Alert' risk communications issued for these regions. Two additional alerts have since been issued in 2024 following the seizure in Dublin of another nitazene powder (protonitazene) and the identification of N-pyrrolidino protonitazene in a Dublin prison setting leading to a small number of overdoses (< 5) [1]. It is too early to speculate on the long-term impact of nitazenes in Ireland, but this is an area requiring intensive monitoring. Nitazenes sold as falsified medicines and as other drugs in the United Kingdom and Europe [2, 3] as well as the use of these substances by non-opioid using populations with no tolerance or access to naloxone, is a particular concern. Following reductions in heroin-related issues, the emergence of a synthetic opioid market now appears to be a very real threat for Europe [3]. Synthetic drugs have proliferated in markets during the last decade offering advantages for both the supplier and consumer, such as geographical flexibility to manufacture, ease of transportation, lower cost and higher potency [4]. In addition, there is concern following a dramatic reduction in poppy cultivation in 2023 in Afghanistan, which could lead to potential heroin shortages in Europe [3]. The current situation creates great uncertainty for the direction of future opioid markets that could impact the estimated 19 875 opioid users in Ireland [3, 5]. Ongoing research is key to identify what role synthetic opioids will establish on the Irish market. The HSE has convened a National Red Alert Group consisting of key stakeholders to monitor and respond to synthetic opioids. Frontline services nationally have been advised to convene and begin developing strategies for managing outbreaks. This includes establishing coordination groups and formal reporting of drug market changes or overdose clusters to the HSE. Emergency protocols and preparation work should be developed with people who use drugs to establish communication channels, tailor messaging and adapt safety plans to individual situations [6, 7]. The Irish nitazene outbreaks are examples of how these substances can emerge without warning and sporadically on the market. Outbreaks require urgent responses and, in the Irish case, current structures had to be adapted without unwieldy policy amendments. Commentary on synthetic opioids in the United Kingdom sees experts call on government to find the political capacity to facilitate policies to reduce harms [8]. Echoing this, significant work was required by a small Irish coordination group who adapted current roles to focus on the outbreaks. This approach will not be sustainable on a long-term basis, emphasizing the need for political prioritization. Increased budget allocation should be provided to improve early warning mechanisms, to expand harm reduction and treatment responses and to enhance drug checking through a dedicated drug-monitoring laboratory. Nicki Killeen: Conceptualization (equal); project administration (equal); writing—original draft (equal); writing—review and editing (equal). Rodney Lakes: Writing—review and editing (equal). Mairead Webster: Writing—review and editing (equal). Sarah Killoran: Writing—review and editing (equal). Sinead McNamara: Writing—review and editing (equal). Pierce Kavanagh: Writing—review and editing (equal). Marie Eagleton: Writing—original draft (equal). Seamus Mc Cormac: Writing—review and editing (equal). Eva Maria Micheau: Writing—review and editing (equal). Adrian Moughty: Writing—review and editing (equal). Cathal O'Donnell: Writing—review and editing (equal). Martin O'Reilly: Writing—review and editing (equal). Gavin Doyle: Writing—review and editing (equal). Sean O'Rourke: Writing—review and editing (equal). Sally Downing: Writing—review and editing (equal). Caoimhe Flynn: Writing—review and editing (equal). Eamon Keenan: Conceptualization (equal); writing—original draft (equal); writing—review and editing (equal). No funding was received for this work. None.