Acute Intoxications and Fatalities Associated With Benzimidazole Opioid (Nitazene Analog) Use: A Systematic Review

Montanari, Eva; Madeo, Graziella; Pichini, Simona; Busardò, Francesco Paolo; Carlier, Jérémy

doi:10.1097/ftd.0000000000000970

Cited by 43 publications

(27 citation statements)

References 44 publications

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“…Some of the common neurological effects due to the intake of SCs are euphoria, increased drive, loquacity, psychomotor agitation, hallucinations, increased alertness, empathy, energy, paranoia, delirium [ 14 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

Daziani

Faro

Montana

et al. 2023

IJMS

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According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances’ cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.

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Section: Introductionmentioning

confidence: 99%

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

Daziani

Faro

Montana

et al. 2023

IJMS

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“…11,21 Several reports of overdose deaths in the United States have been linked to the emergence of these compounds, including isotonitazene, protonitazene, etonitazene, metonitazene, etodesnitazene, and N-piperidinyl etonitazene. [4][5][6][7][8][9][10][11]22,23 Tablets manufactured to look like Food and Drug Administration (FDA)-approved oxycodone HCl 30 mg tablets and those that are round, blue, half-scored, and debossed with "M" on the unscored side and "30" on the scored side (Supporting Information Figure S1) have been found to contain heroin, fentanyl, and fentanyl analogs using traditional laboratory analyses by FDA's Forensic Chemistry Center (FCC)…”

Section: Introductionmentioning

confidence: 99%

“…9,21,[26][27][28][29] The screening and identification of 2-benzylbenzimidazole-type compounds in biological fluids using reversed-phase LC-MS/MS have also been undertaken. 23 Based on the keyword search of "nitazene" in scientific literature via PubMed, Google Scholar, and Web of Science, analysis of these compounds using portable instrumentations such as direct analysis in real time with thermal desorption mass spectrometer (DART-TD-MS) and handheld Raman spectrometers utilizing surface-enhanced Raman scattering spectroscopy (SERS) has not been identified to date.…”

Section: Introductionmentioning

confidence: 99%

“…Like other opioids such as fentanyl, brorphine, 19 2‐methyl AP‐237 20 and others, nitazene‐type compounds are known to cause respiratory depression, which can lead to apnea, respiratory arrest, and death 11,21 . Several reports of overdose deaths in the United States have been linked to the emergence of these compounds, including isotonitazene, protonitazene, etonitazene, metonitazene, etodesnitazene, and N ‐piperidinyl etonitazene 4–11,22,23 …”

Section: Introductionmentioning

confidence: 99%

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Rapid screening of 2‐benzylbenzimidazole nitazene analogs in suspect counterfeit tablets using Raman, SERS, DART‐TD‐MS, and FT‐IR

Kimani

Kern

Lanzarotta

et al. 2023

Drug Testing and Analysis

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Developing methods to rapidly screen for novel synthetic 2-benzylbenzimidazole opioids, also known as nitazenes, has become increasingly important due to their high potency. These compounds have potency comparable or exceeding that of fentanyl by up to 10 times and have been implicated in approximately 5% of all drug overdose deaths in the United States in 2021. This paper details the authenticity determination of suspect tablets and the identification of three nitazene analogs (N-pyrrolidino etonitazene, isotonitazene, and etodesnitazene) in suspect tablets seized at a mail facility using Raman and surface-enhanced Raman scattering (SERS) with handheld devices, portable Fourier transform infrared spectrometer (FT-IR), and a direct analysis in realtime ambient ionization coupled to a thermal desorption unit and a mass spectrometer (DART-TD-MS). These methods are rapid and excellent for screening opioids in suspect tablets but could not fully determine the exact structure of some of the nitazene analogs present due to spectral similarities or similar fragmentation patterns.Liquid chromatography-mass spectrometry (LC-MS) confirmed the presence of these nitazene compounds in addition to other opioids/drugs that were in trace quantities. The quantitative high-performance liquid chromatography coupled with ultraviolet (HPLC-UV) detection experiments determined that the suspect tablets contained an average of 0.817 mg of N-pyrrolidino etonitazene per tablet. The results obtained reveal that the simultaneous deployment of these complementary and orthogonal portable analytical techniques as part of a workflow allows suspect tablets to be screened and nitazene-type drugs to be identified in suspect counterfeit tablets at remote sampling sites.

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“…Besides synthetic cannabinoids, other new psychoactive substances (NPS)-adulterated classical drugs of abuse have provoked a wave of fatal intoxications around the world. Fentanyl and its analogues were employed for decades as heroin adulterants; but recently “nitazenes”, new synthetic benzimidazole opioids with high potencies, are found as common opioid-cutting agents [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances

Trana

Berardinelli

Montanari

et al. 2022

IJMS

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Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer’s profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations’ websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according to the criteria described in the method section. The remaining 117 records were further assessed for eligibility to exclude articles without sufficient data. Finally, 79 studies were classified as “non-biological” (n = 35) or “biological” (n = 35 case reports; n = 9 case series) according to the samples investigated. Although the seized samples analyses revealed the presence of well-established adulterants such as levamisole for cocaine or paracetamol/acetaminophen for heroin, the reported data disclosed new adulteration practices, such as the use of NPS as cutting agents for classic drugs of abuse and other NPS. For example, heroin adulterated with synthetic cannabinoids or cocaine adulterated with fentanyl/fentalogues raised particular concern. Notably, adulterants play a role in some adverse effects commonly associated with the primary drug, such as levamisole-adulterated cocaine that may induce vasculitis via an autoimmune process. It is essential to constantly monitor adulterants due to their changing availability that may threaten drug consumers’ health.

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Acute Intoxications and Fatalities Associated With Benzimidazole Opioid (Nitazene Analog) Use: A Systematic Review

Cited by 43 publications

References 44 publications

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

Rapid screening of 2‐benzylbenzimidazole nitazene analogs in suspect counterfeit tablets using Raman, SERS, DART‐TD‐MS, and FT‐IR

Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances

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