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The rapidly evolving crisis of Novel Synthetic Opioids (NSOs) poses a serious and growing threat for global public health. NSOs include prescription/non-prescription opioids (fentanyl, non-fentanyl analogues), herbal derivatives, and other emerging analogues that are of critical concern due to their high potency, misuse potential, and addiction and intoxication risk. There remains an important gap in real-time, systematic monitoring of NSOs emergence, especially in online communities where these substances appear for the first time. This study aimed to employ the NPSfinder^® automated web-crawling tool to detect, monitor, analyse, and evaluate the evolving NSOs scene. Methods: Data were collected during two time-periods, i.e., 2017–2019 and 2023, from selected high traffic psychonaut online platforms to better understand trends in opioids market evolution and adaptability and compare NPSfinder^® findings with other well-known Early Warning Systems (EWSs) databases to assess detection overlap and early identification capacity. Results: Within the selected time-periods, a total of 446 NSOs were detected by NPSfinder^®; fentanyl analogues (n = 249) were dominant, with a notable rise in non-fentanyl analogues, especially nitazene-like compounds, in 2023. Over 57% of these NSOs were not captured by any of the other EWSs, confirming the tool’s strong capacity to identify early threats. Conclusions: Overall, the low overlap across EWS databases underscores the global challenges in comprehensive opioid detection and surveillance. Future studies should integrate web-crawler findings with real-world datasets. It will be vital to combine these efforts with toxicological, mortality, and clinical outcome analyses, especially for emerging research compounds, to inform targeted harm-reduction strategies.

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