RESUMEN
BACKGROUND: New synthetic opioids (NSO) constitute one of the fastest-growing group of New Psychoactive Substances, which emerged on the illicit drug marker in the second half of 2000's. The most popular and the largest NSO subgroup are high potency fentanyl and its analogs. Subsequent to core-structure scheduling of fentanyl-related substances many opioids with different chemical structures are now emerging on the illicit drug market, rendering the landscape highly complex and dynamic. METHODS: PubMed, Scopus and Google Scholar were searched for appropriate articles up to December 2022. Moreover, a search for reports was conducted on Institutional websites to identify documentation published by World Health Organization, United Nations Office on Drugs and Crime, United States Drug Enforcement Administration, and European Monitoring Centre for Drugs and Drug Addiction. Only articles or reports written in English were selected. RESULTS: Non-fentanyl derived synthetic opioids, i.e., 2-benzylbenzimidazoles (nitazenes), brorphine, U-compounds, AH-7921, MT-45 and related compounds are characterized, describing them in terms of available forms, pharmacology, metabolism as well as their toxic effects. Sample procedures and analytical techniques available for detection and quantification of these compounds in biological matrices are also presented. Finally, as overdoses involving highly potent NSO may be difficult to reverse, the effectiveness of naloxone as a rescue agent in NSO overdose is discussed. CONCLUSIONS: Current review presents key information on non-fentanyl derived NSO. Access to upto-date data on substances of abuse is of great importance for clinicians, public health authorities and professionals performing analyses of biological samples.