Novel psychoactive substances: clinical challenges and therapeutic approaches

Introduction : New psychoactive substances (NPS) constitute a dynamic and diverse class of compounds marked by ongoing structural changes and expanding variability. Recent trends encompass newly developed synthetic cannabinoids, designer benzodiazepine derivatives, emerging dissociative agents, next-generation psychedelics, and highly potent synthetic opioids, as well as semisynthetic and plant-based substances such as kratom. Aim : To examine current trends and emerging developments within the NPS landscape, with a particular focus on newly identified substances, their mechanisms of action, and the clinical risks they pose. Materials and methods : A narrative review of current scientific literature and toxicological data was performed. Relevant publications were identified through nonsystematic searches of PubMed, Scopus, and Web of Science, supplemented by reports from international early warning systems, with an emphasis on newly recognized classes of NPS, their structural derivatives, and their clinical management. Results : Recent advances in the field of NPS are marked by greater molecular variability, strong receptor activity, and unpredictable pharmacokinetic behavior. Many newly developed synthetic cannabinoids function as full CB1 receptor agonists-unlike traditional cannabinoids-leading to severe clinical outcomes such as seizures, psychosis, and cardiovascular disturbances. Novel benzodiazepine-like compounds exhibit considerable toxicity even at low doses, while emerging dissociative agents and psychedelics are linked to significant neuropsychiatric effects. Synthetic opioids constitute a particularly high-risk subgroup due to their exceptional potency and narrow therapeutic window, and certain fentanyl analogues can induce fatal respiratory depression at microgram levels. Conclusion : A key clinical concern is the frequent occurrence of polydrug use, alongside the limited ability of standard toxicology screens to detect many NPS, which necessitates the use of more advanced analytical approaches. Management remains largely supportive and nonspecific, and most therapeutic recommendations are extrapolated from conventional substance use disorders. Ongoing surveillance and timely updates of toxicological knowledge are crucial to address the rapidly evolving and highly dynamic NPS market.