The annual number and incidence rate of NPS poisonings reported to the DPIC strongly increased from 2012 to 2025, representing approximately 4300 NPS poisonings. During a 14‐year period the predominant categories of NPS, and the specific NPS involved in these poisonings, varied. A notable increase in health incidents involving NPS was also reported by Monitor Drug Incidents (MDI), a sentinel network tracking acute drug‐related health incidents in the Netherlands, with details collected from medical services like emergency departments, ambulances, forensic physicians and first‐aid posts at large events [18]. The national rise in NPS presence in the Netherlands is supported by various indicators, including data from the Dutch National Drug Monitor, drug‐checking services and wastewater‐based epidemiology. These sources point to a broad and evolving range of NPS, spanning multiple chemical classes and psychoactive profiles, and an increasing prevalence of use, especially among ‘clubbers’ [9, 19, 20, 21, 22, 23, 24, 25].

In other European countries, an increased number of NPS consumer samples submitted to drug‐checking programs has also been reported [26, 27]. The available evidence indicates that most NPS samples do contain the expected substance, although reliability varies across years and for specific NPS. Some NPS appear more prone to substitution or adulteration than others. Data from the Dutch drug‐checking service indicated that between 2018 and 2022, 90% of consumer‐submitted samples (containing recreational drugs, including NPS) contained the expected substance [28]. The reliability of self‐reported NPS use is further supported because the Dutch government generally does not prosecute individuals for the possession or use of small amounts of controlled substances [3], reducing a patient's likelihood of concealing drug use.

A systematic nationwide overview for NPS‐related fatalities is currently lacking in the Netherlands. Therefore, the number of deaths attributable to the use of NPS is unknown [29]. Nevertheless, several case reports describing fatal intoxications involving NPS have been published over the years in our country [13, 30].

Not all available data sources show a continued increase in the presence of NPS on the drug market. Data from European law enforcement agencies showed that between 2017 and 2020 the number of NPS seizures declined, while the total quantity fluctuated. Seizures increased in 2021 and 2023, with seized quantities reaching a historical peak in 2023 [1]. In 2022, The highest seized volume was reported in the Netherlands (24 613 kg) [31]. In addition, the number of ED visits for NPS poisoning peaked in 2014–2015, possibly associated with an increased awareness of NPS amongst physicians and funded projects to analyze NPS exposures, but have declined more recently [4, 7]. However, identifying NPS poisonings in multi‐center retrospective database research may be challenging, possibly leading to an underestimation of the prevalence of NPS poisonings.

From 2020 onwards, we observed a strong increase in the number of poisonings involving cathinones and benzodiazepines. Cathinones now dominate the European NPS market, as reflected by their position as the second‐largest NPS category monitored by the EU Early Warning System and the percentage and overall quantity of material seized by law enforcement agencies [1]. The widespread availability and structural diversity of cathinones may contribute to an increase in associated health incidents, as supported by our data. Compared with cathinones, benzodiazepine‐related NPS are a relatively small category (38 individual substances notified to the EUDA up to 2024), and the number and quantities seized are limited. As drug‐checking programs only monitor samples offered by consumers, often involving ‘party drugs’, benzodiazepines are rarely detected [9]. However, the incidence of poisonings with benzodiazepine‐related NPS is increasing globally [12, 32, 33, 34, 35, 36]. The under‐reporting of poisonings involving these substances may be linked to the limited availability of validated analytical methods, misinterpretation of toxicological results or insufficient awareness regarding the existence of this NPS category [37]. Consequently, PCCs were among the first to report health incidents involving NPS of the benzodiazepine category [12, 32, 34].

In contrast to other NPS categories, we observed relatively few poisonings involving cannabinoids (n = 150) and opioids (n = 131), although the number of poisonings has increased in recent years. Cannabinoids are the largest NPS category monitored by the EU Early Warning System and are commonly involved in health incidents in many countries [38]. Their contrasting low presence in the Netherlands may be attributed to the easy accessibility of cannabis in Dutch coffeeshops, which likely reduces the use of (semi‐)synthetic cannabinoids [39]. However, we recently observed an increase in the number of poisonings with edibles containing the semi‐synthetic cannabinoids hexahydrocannabinol (HHC) and tetrahydrocannabiphorol (THCP) [40].

Poisonings with opioids were dominated by ODT (73% of all opioid poisonings), while exposures to other variants were only sporadically reported in earlier years. While deaths from ODT poisoning have only been reported in the context of polydrug use [41, 42], most cases still resulted in moderate to severe symptoms, often requiring hospitalization [43]. The low number of opioid poisonings contrasts with the broader European context, where 88 opioids have been identified since 2009 (EUDA, 2025). Opioid‐related NPS pose a significant public health threat owing to their high potential for respiratory depression and associated mortality [44]. This mainly concerns fentanyl derivatives and benzimidazole (nitazene) opioids. In recent years, multiple deaths have been associated with these substances. In addition, we have observed poisonings with nitazenes since 2024, followed by poisonings with methiodone (IC‐26) since 2025. Opioid‐related NPS poisonings may be under‐reported because these substances are increasingly present as adulterants in samples sold as prescription medication, leaving users and healthcare providers unaware of the true exposure [1].

We observed a temporal variation in both dominant NPS categories and the specific NPS involved in poisonings. For example, phenazepam poisonings were only reported between 2014 and 2018. Its scheduling in the Netherlands in 2017 likely contributed to the subsequent decline of reported health incidents. A similar pattern was seen with 4‐FA that peaked in 2016 (n = 50) but nearly disappeared from 2020 to 2022. This decrease may be partly explained by its regulation in 2017, which was preceded by extensive media coverage of severe poisonings [16]. Negative media coverage likely discouraged 4‐FA use, contributing to a decline in poisonings. However, media exposure may also increase PCC consultations by raising awareness among healthcare providers. This might have occurred with alpha‐pyrrolidinovalerophenone (α‐PVP), which received intense media attention in 2016 for causing extremely violent ‘zombie‐like’ behavior. A peak in reported suspected poisonings (n = 10) was observed that year, followed by a decline thereafter. As most cases lacked analytical confirmation, clinical features could not be definitively linked to α‐PVP. Moreover, excited delirium, commonly reported in these cases, can be caused by various psychoactive substances, including established recreational drugs and alcohol [45]. It is plausible that media narratives influenced clinical suspicion and reporting bias toward α‐PVP.

Another factor influencing poisoning trends is NPS availability and composition. In 2019, most 2C‐B samples analyzed by Dutch drug‐checking services were adulterated or contained no 2C‐B at all [46]. This may have negatively influenced consumer demand for 2C‐B, resulting in a decline in overall use and associated poisonings. Conversely, adulterated NPS can increase health risks when users are unaware of the actual contents of pills or powders. Following the 2021 ban on 3‐MMC, reported poisonings initially declined, but rose again in 2023. Data from Dutch drug‐checking services revealed that many samples sold as 3‐MMC actually contained other legal cathinones, like 3‐chloromethcathinone (3‐CMC) or 2‐methylmethcathinone (2‐MMC) [47], which may differ in their potency and pharmacokinetics, thereby potentially increasing overdose risk.

A significant increase in the annual incidence rate of NPS poisonings occurred in 2020, which was when the COVID pandemic started in the Netherlands. Whether this increase was caused by the pandemic is open to debate. Other possible causes include variables not included in the time series analysis, such as greater ease in obtaining NPS products on the market in terms of price, the number of websites and advertising on social networks. Evidence on the impact of the COVID pandemic on the Dutch NPS market is limited and heterogeneous. An analysis of online drug markets indicated shifts in substance availability during the first lockdown, with reduced activity for stimulants (e.g. amphetamine, cocaine, MDMA) and a relative increase for substances such as 2C‐B, ketamine and LSD [48]. Other studies suggest that 3‐MMC use increased among certain groups during the pandemic, while 2C‐B use remained stable [49, 50], and 4‐FA use declined and remained low thereafter [51]. In addition, data from drug‐checking services showed a reduced number of sample submissions during 2020–2021, followed by a marked increase in 2022, particularly for 3‐MMC [52, 53, 54]. Overall, these findings suggest that the pandemic influenced drug markets and use patterns, which may have resulted in an increase of NPS poisonings. Finally, a seasonal pattern was observed in the number of reported NPS poisonings, being highest in July and December. A high incidence of drug‐related health incidents during the summer months has been described previously [55, 56].