INTRODUCTION: The rapid proliferation of new psychoactive substances (NPS) presents a major challenge to drug control systems. Unlike traditional controlled substances, NPS are synthetic compounds engineered to bypass existing regulations, raising serious public health concerns due to their high potency and unpredictable toxicity. To support a coordinated European response, the REITOX (Réseau européen d'information sur les drogues et les toxicomanies) network brings together national focal points from EU Member States, Norway, Türkiye and the European Commission.

OBJECTIVE: To provide a comparative overview of legislative frameworks and regulatory responses to NPS across REITOX Member Countries within the European Union.

METHODS: We conducted a cross-national analysis of legal texts, procedures for scheduling new substances, and alignment with international and EU legislation. The role of the Early Warning System (EWS), coordinated by the European Union Drugs Agency (EUDA) and supported by the REITOX network, was also examined.

RESULTS: The analysis revealed substantial variation among REITOX member states in legal approaches, timelines, and integration with EU-level mechanisms. REITOX focal points play a central role in information exchange and in supporting the EWS for early detection and coordinated responses to NPS-related threats.