Toxicological aspects of emerging nitazene analogues as a new threat to the synthetic drug landscape

The emergence of New Psychoactive Substances (NPSs) has become a growing concern for global public health and security. The nitazene analogues, a group of synthetic opioids that could present a higher potency than morphine and fentanyl, have been associated with fatal overdoses. Nitazene analogues have been frequently found on the drug market, often combined with other substances, which significantly increases the risk of poisoning. This work aims to review the toxic effects and abuse potential of nitazene analogues, through the review of scientific articles and technical notes, from 2020 to 2024, in the databases PubMed/Medline, Scielo, and Google Scholar. The desired effects associated with the use of nitazene include euphoria and relaxation, but they can also lead to undesirable effects, such as edema, dizziness, drowsiness and respiratory depression, in addition to the risk of cardiac arrest. Prolonged exposure is associated with the development of dependence and withdrawal symptoms after abrupt cessation. One of the main clinical concerns is the difficulty in the use of traditional overdose reversal methods, such as naloxone, due to the higher potency of some analogues compared to morphine or heroine. Laboratory analysis is one of the main challenges due to the low concentration of nitazene analogues in samples. The complexity of toxicity, abuse potential, and difficulties in reversing intoxication reinforce the need for specific intervention protocols and training for health professionals on the risks of synthetic opioids. Better understanding the toxicokinetics and effects of nitazenes group are essential steps to develop effective drug policies and minimize the harm to human health caused by these compounds.