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Review
. 2025 Oct 15.
doi: 10.1111/dar.70040. Online ahead of print.

Behavioural Effects and Naloxone Effectiveness With New Synthetic Opioids

Suzanne Nielsen  1 , João Pedro Silva  2 , Jermaine D Jones  3 , Alex Krotulski  4 , Dilkushi Poovendran  5 , Deusdedit Muzangizi  5 , Gilles Forte  6 , Jason White  7 , Sandra D Comer  3
Affiliations
Review

Behavioural Effects and Naloxone Effectiveness With New Synthetic Opioids

Suzanne Nielsen et al. Drug Alcohol Rev. .

Abstract

Introduction: The global drug market has seen an emergence of potent synthetic opioids, including benzimidazole-derived substances known as nitazenes. These compounds have been implicated in fatal and non-fatal overdoses. This review aims to synthesise current evidence on the pharmacological effects, potency and naloxone responsiveness of new synthetic opioids, with a focus on synthetic opioids evaluated for international control since 2020. It highlights key findings that can inform our understanding of these substances and inform harm reduction strategies.

Methods: A narrative review was conducted using critical reviews from the World Health Organization Expert Committee on Drug Dependence and supplementary literature. Data extraction focused on pharmacological profiles, behavioural effects, potency estimates, and naloxone effectiveness.

Results: Thirteen synthetic opioids were examined, with potencies ranging from similar to morphine to exceeding that of fentanyl. Naloxone demonstrated efficacy in reversing overdose symptoms for most substances, although higher doses or infusions were occasionally required.

Discussion and conclusions: The variability in nitazene potency and common unintended use underscores the need for widespread education, broad naloxone access and robust drug-checking initiatives. Key challenges include the detection of nitazenes in polydrug contexts and their presence in substances sold as other drugs, including falsified pharmaceuticals. Emerging evidence suggests that naloxone can reverse acute poisonings with benzimidazole opioids. However, no studies have examined the effectiveness of medications for treating opioid use disorder (e.g., methadone, buprenorphine, naltrexone) in people who are physically dependent on nitazenes. Future research should address this important knowledge gap.

Keywords: antinociception; naloxone; nitazenes; potency; synthetic opioids.

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References

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    1. A. Roxburgh and S. Nielsen, “Twenty‐Year Trends in Pharmaceutical Fentanyl and Illicit Fentanyl Deaths, Australia 2001‐2021,” International Journal on Drug Policy 109 (2022): 103854.

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