Commentary on Bade et al.: Threat of nitazenes and other potent synthetic opioids—Is Europe prepared? Time to respond and to learn

IF 5.3 1区 医学 Q1 PSYCHIATRY
Addiction Pub Date : 2025-07-17 DOI:10.1111/add.70150
Isabelle Giraudon, Ana Gallegos, Senad Handanagić, Jane Mounteney
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Given the high potency of nitazenes, the low expected use dose, the still small number of regular users in most countries and the dilution of a wastewater treatment plant due to the size of the catchment area, the presence of nitazenes may be challenging to detect if relying primarily on wastewater analysis.</p><p>Over reliance on one data source increases the risk of missing local outbreaks of poisonings [<span>1, 2</span>]. Reports from Germany, France, Ireland and the Netherlands illustrate that the detection of new synthetic opioids has been confirmed using triangulation of multiple data sets [<span>3-6</span>]. The European Union Early Warning System (EWS) on new psychoactive substances (NPS) is Europe's flagship mechanism for detecting NPS, such as nitazenes, and it draws on multiple information sources. Alongside the EWS, the European Union Drugs Agency (EUDA) monitoring framework provides a robust analysis by analysing seizure data, data from drug-related death mortality registries as well as the European web survey on drugs (EWSD), along with city level sources, such as wastewater analysis, analysis of syringe residues, samples collected by drug-checking services and acute toxicity presentations to hospitals [<span>7</span>].</p><p>Since 2019, the EU EWS has reported the emergence of 23 different nitazenes detected in at least 21 European countries [<span>8, 9</span>]. The quantities of nitazenes seized in 2023 tripled compared to 2022, and the number of tablets seized containing nitazenes doubled in 2024 compared to 2023 [<span>8, 9</span>]. These include nitazenes found in counterfeit medicines. Syringe residue analysis identified nitazenes in Tallinn, Estonia (34% in 2023 and 35% in 2024), in Riga, Latvia (74% and 33%); and in Klaipeda, Lithuania (4% in 2024). The type of nitazenes found were: isotonitazene, metonitazene, protonitazene, N-Desethyletonitazene, protonitazepyne, etonitazepyne. Most syringes contained at least one other drug, a signal of potentially common polysubstance use. In 2023 and 2024, drug-checking services sporadically detected nitazenes in samples brought on-line and given by the buyers to the services for content confirmation. In the 2024 European web survey on drugs, participants in Germany, Austria, Latvia, Sweden and Spain reported having used nitazenes in the past 12 months [<span>10</span>].</p><p>The European Drug Emergencies Network hospital in Riga, Latvia, reported 21 presentations in 2023 and 2024. The median age was 37, 17 of 21 were males. The most commonly identified nitazenes were etonitazene, metonitazene and etodesnitazene. The most common substances reported alongside nitazenes were benzodiazepines, cannabis and cocaine. Hospitals in Munich, Germany (in 2021), and Utrecht, the Netherlands (in 2024), reported one case each of nitazenes in acute drug toxicity presentations.</p><p>Nitazenes drove the increase in drug-related deaths in Latvia and Estonia in 2022 to 2023 [<span>11</span>], and were implicated in 101 of 154 (66%) of the cases in Latvia in 2023, decreasing to 33 of 76 (43%) in 2024. In Estonia, although numbers peaked in 2023, (61 of 119 cases, 52%), nitazenes were still implicated in 42 of 100 cases (42%) in 2024. Norway (June 2023–August 2024) and Sweden (January 2023–September 2024) reported, respectively, 34 and 30 deaths associated with nitazenes [<span>8</span>].</p><p>These examples of different methods employed to detect nitazene use illustrate the value of multi-layered monitoring systems and signal detection tools that combine population and individual level data and that can integrate analysis received directly from people using drugs. Improvement of the toxicology capacity—including more and better <i>post-mortem</i>, drug-checking, wastewater analysis and analytical confirmations from forensic and clinical laboratories is crucial to ensure our preparedness for potent—and quickly appearing—new drugs [<span>12</span>]. As highlighted, wastewater and toxicology data need to be triangulated with drug seizure data, information about the availability, purity and prices of drugs from different sources (e.g. bought over the internet or in the streets) [<span>8</span>]. However, a key challenge remains to triangulate these sparse signals, whether from wastewater or other sources and identify ways of transforming them into policy recommendations and evidence-based and innovative actions in Europe and beyond [<span>13-15</span>].</p><p>To conclude, timely, granular and actionable information based on a set of key national-level epidemiological indicators, EWS and city-level data collection methods are allowing policy makers to respond rapidly to drug-related problems. 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引用次数: 0

Abstract

Bade et al. [1] make an important contribution to the potential use of wastewater analysis for monitoring the presence of nitazenes. They state that this approach may be useful for capturing early signals of the presence of these substances (and potentially other highly potent opioids) on a population level, especially when combined with other data sources and systems. Given the high potency of nitazenes, the low expected use dose, the still small number of regular users in most countries and the dilution of a wastewater treatment plant due to the size of the catchment area, the presence of nitazenes may be challenging to detect if relying primarily on wastewater analysis.

Over reliance on one data source increases the risk of missing local outbreaks of poisonings [1, 2]. Reports from Germany, France, Ireland and the Netherlands illustrate that the detection of new synthetic opioids has been confirmed using triangulation of multiple data sets [3-6]. The European Union Early Warning System (EWS) on new psychoactive substances (NPS) is Europe's flagship mechanism for detecting NPS, such as nitazenes, and it draws on multiple information sources. Alongside the EWS, the European Union Drugs Agency (EUDA) monitoring framework provides a robust analysis by analysing seizure data, data from drug-related death mortality registries as well as the European web survey on drugs (EWSD), along with city level sources, such as wastewater analysis, analysis of syringe residues, samples collected by drug-checking services and acute toxicity presentations to hospitals [7].

Since 2019, the EU EWS has reported the emergence of 23 different nitazenes detected in at least 21 European countries [8, 9]. The quantities of nitazenes seized in 2023 tripled compared to 2022, and the number of tablets seized containing nitazenes doubled in 2024 compared to 2023 [8, 9]. These include nitazenes found in counterfeit medicines. Syringe residue analysis identified nitazenes in Tallinn, Estonia (34% in 2023 and 35% in 2024), in Riga, Latvia (74% and 33%); and in Klaipeda, Lithuania (4% in 2024). The type of nitazenes found were: isotonitazene, metonitazene, protonitazene, N-Desethyletonitazene, protonitazepyne, etonitazepyne. Most syringes contained at least one other drug, a signal of potentially common polysubstance use. In 2023 and 2024, drug-checking services sporadically detected nitazenes in samples brought on-line and given by the buyers to the services for content confirmation. In the 2024 European web survey on drugs, participants in Germany, Austria, Latvia, Sweden and Spain reported having used nitazenes in the past 12 months [10].

The European Drug Emergencies Network hospital in Riga, Latvia, reported 21 presentations in 2023 and 2024. The median age was 37, 17 of 21 were males. The most commonly identified nitazenes were etonitazene, metonitazene and etodesnitazene. The most common substances reported alongside nitazenes were benzodiazepines, cannabis and cocaine. Hospitals in Munich, Germany (in 2021), and Utrecht, the Netherlands (in 2024), reported one case each of nitazenes in acute drug toxicity presentations.

Nitazenes drove the increase in drug-related deaths in Latvia and Estonia in 2022 to 2023 [11], and were implicated in 101 of 154 (66%) of the cases in Latvia in 2023, decreasing to 33 of 76 (43%) in 2024. In Estonia, although numbers peaked in 2023, (61 of 119 cases, 52%), nitazenes were still implicated in 42 of 100 cases (42%) in 2024. Norway (June 2023–August 2024) and Sweden (January 2023–September 2024) reported, respectively, 34 and 30 deaths associated with nitazenes [8].

These examples of different methods employed to detect nitazene use illustrate the value of multi-layered monitoring systems and signal detection tools that combine population and individual level data and that can integrate analysis received directly from people using drugs. Improvement of the toxicology capacity—including more and better post-mortem, drug-checking, wastewater analysis and analytical confirmations from forensic and clinical laboratories is crucial to ensure our preparedness for potent—and quickly appearing—new drugs [12]. As highlighted, wastewater and toxicology data need to be triangulated with drug seizure data, information about the availability, purity and prices of drugs from different sources (e.g. bought over the internet or in the streets) [8]. However, a key challenge remains to triangulate these sparse signals, whether from wastewater or other sources and identify ways of transforming them into policy recommendations and evidence-based and innovative actions in Europe and beyond [13-15].

To conclude, timely, granular and actionable information based on a set of key national-level epidemiological indicators, EWS and city-level data collection methods are allowing policy makers to respond rapidly to drug-related problems. Developing integrated approaches is one of the key pillars for preparedness policies, alongside ensuring evidence-based, resilient and agile drug prevention, treatment, and harm reduction services and sustainable funding streams.

Isabelle Giraudon: Conceptualization; data curation; formal analysis; writing—original draft; writing—review and editing. Ana Gallegos: Data curation; validation; writing—review and editing. Senad Handanagić: Formal analysis; validation; writing—review and editing. Jane Mounteney: Conceptualization; formal analysis; validation; writing—review and editing.

None.

巴德等人评论:nitazene和其他强效合成阿片类药物的威胁——欧洲准备好了吗?是时候回应和学习了。
Bade等人对废水分析用于监测nitazene存在的潜在用途做出了重要贡献。他们指出,这种方法可能有助于在人群水平上捕获这些物质(以及潜在的其他强效阿片类药物)存在的早期信号,特别是当与其他数据源和系统结合使用时。鉴于nitazenes的效力高,预期使用剂量低,在大多数国家经常使用的人数仍然很少,并且由于集水区的大小,污水处理厂的稀释,如果主要依靠废水分析,nitazenes的存在可能难以检测。过度依赖一种数据源会增加错过当地中毒暴发的风险[1,2]。来自德国、法国、爱尔兰和荷兰的报告表明,通过对多个数据集进行三角测量,已经证实了新型合成阿片类药物的检测[3-6]。欧盟新精神活性物质(NPS)预警系统(EWS)是欧洲检测nitazene等新精神活性物质的旗舰机制,它利用多种信息来源。除EWS外,欧洲联盟药品管理局监测框架还通过分析缉获数据、来自与毒品有关的死亡死亡率登记处的数据以及欧洲药物网络调查(EWSD),以及城市一级的来源,如废水分析、注射器残留物分析、药物检查服务收集的样本和向医院提交的急性毒性报告,提供了强有力的分析。自2019年以来,欧盟EWS报告称,在至少21个欧洲国家发现了23种不同的nitazene[8,9]。与2022年相比,2023年缉获的nitazene数量增加了两倍,2024年缉获的含有nitazene的片剂数量比2023年增加了一倍[8,9]。其中包括假药中发现的nitazene。通过注射器残留物分析,爱沙尼亚塔林(2023年为34%,2024年为35%)和拉脱维亚里加(74%和33%)分别鉴定出nitazene;立陶宛的克莱佩达(2024年为4%)。发现的nitnitazene的类型有:异硝基甲苯、甲苯硝基甲苯、原硝基甲苯、n -去乙基甲苯硝基甲苯、原硝基甲苯硝基甲苯、乙硝基甲苯硝基甲苯。大多数注射器中至少含有一种其他药物,这是可能普遍使用多种药物的信号。在2023年和2024年,药物检查服务偶尔会在买家带到网上并交给服务部门进行内容确认的样品中检测到nitazene。在2024年的欧洲毒品网络调查中,德国、奥地利、拉脱维亚、瑞典和西班牙的参与者报告说,他们在过去的12个月里使用过nitazene。位于拉脱维亚里加的欧洲药物紧急情况网络医院在2023年和2024年报告了21例病例。中位年龄为37岁,21人中有17人是男性。最常见的nitnitazene是依替硝泽烯、甲替硝泽烯和依替硝泽烯。据报道,与nitazene一起最常见的物质是苯二氮卓类药物、大麻和可卡因。德国慕尼黑(2021年)和荷兰乌得勒支(2024年)的医院分别报告了一例nitazene急性药物毒性病例。在2022年至2023年期间,nitazene推动了拉脱维亚和爱沙尼亚与毒品有关的死亡人数的增加,并与拉脱维亚2023年154例(66%)中的101例(2024年76例)有关,减少到33例(43%)。在爱沙尼亚,尽管数量在2023年达到顶峰(119例中有61例,52%),但2024年100例中仍有42例(42%)涉及nitazene。挪威(2023年6月至2024年8月)和瑞典(2023年1月至2024年9月)分别报告了34例和30例与nitazene bbb有关的死亡。这些用于检测nitazene使用的不同方法的例子说明了多层监测系统和信号检测工具的价值,这些系统和信号检测工具结合了群体和个人层面的数据,并可以整合直接从吸毒者那里获得的分析。提高毒理学能力——包括更多和更好的尸检、药物检查、废水分析以及法医和临床实验室的分析确认——对于确保我们为强有力的、迅速出现的新药危机做好准备至关重要。正如所强调的那样,废水和毒理学数据需要与毒品缉获数据、关于不同来源(例如通过互联网或街头购买)药物的可得性、纯度和价格的信息进行三角测量。然而,一个关键的挑战仍然是对这些来自废水或其他来源的稀疏信号进行三角测量,并确定将其转化为欧洲及其他地区的政策建议和循证创新行动的方法[13-15]。总而言之,基于一套关键国家级流行病学指标、EWS和城市级数据收集方法的及时、细致和可操作的信息使决策者能够迅速应对与毒品有关的问题。 制定综合方法是防范政策的关键支柱之一,同时确保以证据为基础、有复原力和灵活的药物预防、治疗和减少伤害服务以及可持续的资金流。Isabelle Giraudon:概念化;数据管理;正式的分析;原创作品草案;写作-审查和编辑。Ana Gallegos:数据管理;验证;写作-审查和编辑。Senad handanagiki:形式分析;验证;写作-审查和编辑。简·蒙尼:概念化;正式的分析;验证;写作——审阅和编辑。
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来源期刊
Addiction
Addiction 医学-精神病学
CiteScore
10.80
自引率
6.70%
发文量
319
审稿时长
3 months
期刊介绍: Addiction publishes peer-reviewed research reports on pharmacological and behavioural addictions, bringing together research conducted within many different disciplines. Its goal is to serve international and interdisciplinary scientific and clinical communication, to strengthen links between science and policy, and to stimulate and enhance the quality of debate. We seek submissions that are not only technically competent but are also original and contain information or ideas of fresh interest to our international readership. We seek to serve low- and middle-income (LAMI) countries as well as more economically developed countries. Addiction’s scope spans human experimental, epidemiological, social science, historical, clinical and policy research relating to addiction, primarily but not exclusively in the areas of psychoactive substance use and/or gambling. In addition to original research, the journal features editorials, commentaries, reviews, letters, and book reviews.
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