Estonia has spent more than two decades battling some of Europe’s most potent illicit opioids. But Katri Abel-Ollo, PhD, who is the head of the Drugs and Addictions Department at the National Institute for Health Development in Tallinn, Estonia, said the crisis has never felt so unpredictable. Despite working in the field for 24 years, she said the rapid emergence of new synthetic opioids has left even experienced public health officials struggling to prepare for what comes next.

Between 2002 and 2017, Estonia experienced Europe’s worst drug overdose crisis caused by the entry to the illicit market of fentanyl, a synthetic opioid that largely replaced heroin following a supply shortage. The crisis subsided in 2017 after major trafficking operations were dismantled. But fentanyl was soon replaced by other synthetic opioids, including nitazenes and, more recently, cychlorphine.

As one synthetic opioid disappears or becomes less available, another can emerge in its place, often before surveillance systems and harm reduction services have adapted. The rapid turnover of highly potent substances is making it increasingly difficult to identify emerging threats, prevent overdoses, and prepare healthcare services for what comes next.

Newcomers On the Market

Nitazenes, a group of benzimidazole opioids never been approved for medical use, have been detected in Estonia since 2019. Some of these are significantly more potent than heroin and can be up to 10 times more potent than fentanyl.

In 2024, seven new synthetic opioids were formally reported to the EU Early Warning System; all of them were nitazenes. Since 2019, at least 21 EU Member States have reported detecting nitazene. The drugs have been linked to dozens of overdose deaths across Europe, including 62 in Estonia and 101 in Latvia in 2023.

Since 2024, a new group of synthetic opioids called orphines has been reported in Europe. Concerned about the public health risks, the European Union Drugs Agency placed orphines under intensive monitoring in 2025, requiring closer scrutiny of new detections, seizures, toxicologic findings, and suspected harms reported through Europe’s early warning network. The agency subsequently published a report documenting the substance’s emergence and associated risks.

Between August 2024 and March 2026, four EU countries reported a total of 31 deaths, in which exposure to cychlorphine was confirmed. Of those, 24 occurred in Estonia.

“When we think about the harms, the most severe harm is overdose and death, and Estonia has experienced the most harms,” Jo-Hanna Ivers, PhD, an associate professor of addiction in the Discipline of Public Health and Primary Care at Trinity College Dublin in Dublin, Ireland, told Medscape News Europe. “We were used to dealing with heroin, but new synthetic opioids are entering the market and they are becoming more potent each time a derivative is produced.”

A Crisis That Varies Across Europe

Although heroin remains the primary opioid of concern across much of Europe, synthetic opioids are affecting several countries, including Latvia, Sweden, Ireland, France, and the UK. The Baltic region’s experience has shown how rapidly synthetic opioids can take hold of the market and cause harm when heroin supplies decline.

“There is no generic European situation. The nature and severity of the situation varies widely [across countries] and the responses as well,” John-Peter Kools, former senior policy advisor on drug policy at Trimbos Institute, Netherlands Institute of Mental Health and Addiction, told Medscape News Europe. “But the overall trend is clear: Globalization and advancing technology increasingly enable diversification of production and trade of illicit synthetic substances. All countries in Europe face it one way or another, but the trends develop according to local circumstances and their illicit markets.”

For public health authorities, the proliferation of new substances presents an increasingly complex challenge. Harm reduction services, toxicology laboratories, surveillance networks, and early warning systems must continually adapt to drugs that may be unfamiliar, exceptionally potent, or difficult to detect. “How can we get ahead? The trouble with our preparedness is that every time we get a handle on it, a new drug enters the market,” Ivers said. “It’s like a runaway train.”

Despite having differences in their chemical structures, potency, and duration of action, most synthetic opioids generally cause the same types of life-threatening effects when taken in excessive amounts. What is lagging across the continent, though, is widespread hospital screening, with identification of different substances requiring specialist analytical techniques, alongside an understanding of the life of the substances, and managing poly substance use, Ivers said.

To add to the harm of these novel products is that emerging synthetic opioids are frequently mixed with other substances — sometimes without the knowledge of those using them — which might increase the risks of overdosing. “When we think about potency, there are two problems: when the drug comes on its own and when it is laced with other products,” Ivers said. “From a public health perspective, people are using what they think is one drug but it’s another. Our systems aren’t set up to deal with it. We are doomed to fail.”

Naloxone Offers an Immediate Response

As authorities grapple with the changing drug landscape, experts say one of the most effective immediate interventions is expanding access to naloxone, a nonaddictive medication that can temporarily reverse the life-threatening effects of an opioid overdose.

In some countries such as Ireland, naloxone requires a prescription, but Ivers said there was an ongoing community pilot providing it free at the point of contact.

Earlier this month, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use recommended making naloxone nasal spray available without a prescription across the EU. For Ivers, the news was very welcome. “It is a wonder drug. It’s the kind of change we can make today — it’s another form of frontline defense, and we need to get behind it,” she said.

In Estonia, naloxone is widely available through prescription-based take-home programs and provided for free at harm reduction centers and emergency services.

“The main challenge for doctors has been distinguishing between different synthetic opioids,” Abel-Ollo said. “The [question] is whether naloxone works at standard doses or whether additional doses are needed. With nitazenes, the ambulance services were initially quite alarmed because they encountered patients showing clear signs of an opioid overdose, but the usual dose of naloxone did not seem to work.”

Ivers called for stronger surveillance and early warning systems to help European countries identify emerging substances before they cause widespread harm. She said closer coordination between national monitoring systems could improve preparedness, but authorities remain heavily dependent on toxicology findings from people who have already experienced an overdose. “Countries are trying to collate all the signals across systems so we can be as prepared as we can and better understand the harms. The issue is that we are always on the back foot; it’s quite scary.”

Self-reported drug use data are unreliable because users may not know which substances they have taken. While hospitals in Estonia don’t have toxicologic testing facilities, some hospitals are now sending urine samples from patients to the Institute of Forensic Medicine for analysis as part of a research project. The country has also introduced other surveillance measures to track emerging substances and their associated risks.

Abel-Ollo, Ivers, and Kools reported having no financial relationships.