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Cited by 55Forensic Toxicology and Drug AnalysisOpioid Use Disorder TreatmentAlkaloids: synthesis and pharmacology

Non-Fentanyl New Synthetic Opioids—An Update

Zawilska, Jolanta B., Adamowicz, Piotr, Kurpeta, Marta, Wojcieszak, Jakub·2023·Forensic Science International
DOI 10.1016/j.forsciint.2023.111775
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Abstract

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.

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Crossref · 10.1016/j.forsciint.2023.111775

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80 of 80 references verified0 citation errors · 0 not checkable

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  • Like other opioids, nitazenes have a high potential for abuse and dependence through stimulation of the brain's dopaminergic reward system.

    “Like other opioids, nitazenes have a high potential for abuse and dependence through stimulation of the brain’s dopaminergic reward system [27,35].”

    From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [27]

  • Nitazenes have the potential of becoming the drugs of choice in the future, resembling the shift that occurred with fentanyl.

    “Nitazenes have the potential of becoming the drugs of choice in the future, resembling the shift that occurred with fentanyl [27].”

    From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [27]

  • In October 2022, 21 deaths were reported across North America, most of which were co-detected with other drugs, including fentanyl (n = 12), methylamphetamine (n = 12) or benzodiazepines (n = 11).

    “In October 2022, 21 deaths were reported across North America, most of which were co‐detected with other drugs, including fentanyl (n = 12), methylamphetamine (n = 12) or benzodiazepines (n = 11) [1].”

    From Early identification of the use of potent benzylbenzimidazoles (nitazenes) through wastewater analysis: Two years of data from 22 countries (2025) · cites this paper as [1]

  • Nitazenes are often mixed with or sold as other drugs such as heroin, fentanyl, benzodiazepines, methamphetamine, cocaine, or counterfeit medications, and many users remain unaware they are taking nitazenes, markedly increasing the risk of overdose, particularly among opioid-naïve individuals.

    “A major concern is the unintentional consumption of nitazenes, as they are often mixed with or sold as other drugs such as heroin, fentanyl, benzodiazepines, methamphetamine, cocaine, or counterfeit medications (e.g., oxycodone, hydromorphone, Xanax, Dilaudid). Many users remain unaware they are taking nitazenes, markedly increasing the risk of overdose, particularly among opioid-naïve individuals”

    From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [27]

  • Polysubstance use, often involving combinations with fentanyl, methamphetamine, amphetamine, or flualprazolam, further complicates clinical management and increases the risk of synergistic respiratory depression.

    “This polysubstance use, often involving combinations with fentanyl, methamphetamine, amphetamine, or flualprazolam, further complicates clinical management and increases the risk of synergistic respiratory depression [7,12,27].”

    From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [27]

Cites

Flagged first, then by citations

3 of the 83 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Nakamura, 1976, Comparative study of 1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine and its enantiomorphs on analgesic and other pharmacological activities in experimental animals, Arch. Int. Pharmacodyn. Ther., 221, 105
  2. Edison, 2017, Notes from the Field: Counterfeit Percocet-Related Overdose Cluster - Georgia, June 2017, 66, 1119

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Authors
Zawilska, J. B., Adamowicz, P., Kurpeta, M., & Wojcieszak, J.
Affiliations
Medical University of Lodz (PL)
Corresponding author
Zawilska, Jolanta B.
ORCID
Venue
Forensic Science International
Publisher
Elsevier BV
Published
2023-08
Volume
349
Pages
111775
ISSN
0379-0738 (ISSN-L)
DOI
10.1016/j.forsciint.2023.111775
OpenAlex
W4382404956
Cited by
55
References
83
Citations by year
2026: 15 · 2025: 28 · 2024: 11 · 2023: 1
FWCI
2.19
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Forensic Science International (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical University of Lodz
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Alkaloids: synthesis and pharmacology
Keywords
new psychoactive substances, nitazenes, opioid pharmacology, opioid metabolism, opioid toxicity, opioid overdose, naloxone, drug detection in biological samples, illicit drug markets
MeSH terms
Analgesics, Opioid, Fentanyl, Humans, Naloxone, Opioid-Related Disorders, Illicit Drugs, Drug Overdose

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