An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA

Tyndall, Joseph A.; Gerona, Roy; Portu, Giuliano De; Trecki, Jordan; Elie, Marie-Carmelle; Lucas, Judith K.; Slish, John; Rand, Kenneth H.; Bazydlo, Lindsay A.L.; Holder, Martina; Ryan, Matthew F.; Myers, Paul; Iovine, Nicole M.; Plourde, Michelle; Weeks, Emily; Hanley, James R.; Endres, Gregory W.; Germaine, Danielle St.; Dobrowolski, Paul J.; Schwartz, Michael D.

doi:10.3109/15563650.2015.1100306

Cited by 66 publications

(36 citation statements)

References 10 publications

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“…An EC 50 value of 3.45 nM (1.96–6.14) was determined for compound 14 (Table ), which is in agreement with the low EC 50 value of 7.4 ± 1.5 nM reported by Wiley et al , which was determined by the binding of a slowly hydrolysable GTP analog to the Gα‐subunit using [ 35 S]GTPγS turnover assay, instead of the β‐arr2 recruitment assay used in this study. Hydrolysis metabolite 16 has been identified as a hydrolysis product of parent compounds 14 and 15 in a number of studies in urine and hair of abusers . Metabolite 16 clearly retains activity (EC 50 = 155 nM), although with a 45‐fold impaired potency when compared to the parent compounds (Table ).…”

Section: Resultsmentioning

confidence: 99%

Functional evaluation of carboxy metabolites of synthetic cannabinoid receptor agonists featuring scaffolds based on L‐valine or L‐tert‐leucine

Wouters

Mogler

Cannaert

et al. 2019

Drug Testing and Analysis

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Indole‐ and indazole‐based synthetic cannabinoid receptor agonists (SCRAs), featuring valine or tert‐leucine substituents, are commonly abused new psychoactive substances (NPS). A major metabolic pathway for these SCRAs is hydrolysis of the terminal amide or methylester functionalities. Although these hydrolysis products were already detected as main ingredients in some “legal highs,” these metabolites are often poorly characterized. Here, we report a systematic investigation of the activity of 7 common hydrolysis metabolites of 15 SCRAs featuring scaffolds based on L‐valine or L‐tert‐leucine in direct comparison to their parent compounds. An activity‐based cannabinoid receptor 1 (CB1) bio‐assay was used for activity profiling of SCRAs and their metabolites in a stable HEK293T cell system. The recruitment of β‐arrestin2 to the activated CB1 (each fused to one part of a split Nanoluciferase) was provoked by adding the (putative) SCRAs. Luminescence of the functionally complemented luciferase was monitored by a 96‐well plate‐reader. The major hydrolysis metabolites of 5F‐AB‐PINACA, ADB‐CHMICA, ADB‐CHMINACA, ADB‐FUBICA, and their methyl‐ and ethylester derivatives showed no detectable CB1 activation at concentrations up to 1 μM. On the other hand, metabolites of 5F‐ADB‐PINACA, AB‐CHMINACA, and ADB‐FUBINACA did retain activity, although significantly reduced as compared to the parent compounds (EC50 values >100 nM). Activity‐based characterization of SCRAs and their metabolites at CB1 may not only allow a better insight into the complex interplay between SCRAs and their metabolites in intoxications, but may also allow application of the concept of “activity equivalents” present in biological fluids or, alternatively, in confiscated materials.

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Section: Resultsmentioning

confidence: 99%

Functional evaluation of carboxy metabolites of synthetic cannabinoid receptor agonists featuring scaffolds based on L‐valine or L‐tert‐leucine

Wouters

Mogler

Cannaert

et al. 2019

Drug Testing and Analysis

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“…Because of this, cases of acute poisoning, accidental overdose, and unforeseen adverse reactions associated with NPS use have become an increasing problem at emergency departments (EDs) and intensive care units (ICUs) . To study the occurrence and health hazards of newly emerging drugs of abuse in Sweden, the STRIDA project was started in 2010 .…”

Section: Introductionmentioning

confidence: 99%

Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances

Bäckberg

Jönsson

Beck

et al. 2017

Drug Testing and Analysis

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The web-based open sale of unregulated new psychoactive substances (NPS) has shown a steady increase in recent years. Analysis of drug products sold as NPS is useful to confirm the true chemical contents, for comparison with the substances detected in corresponding body fluids, but also to study drug trends. This work describes the examination of 251 drug products that were randomly submitted for analysis in 173 cases of suspected NPS-related intoxications in the Swedish STRIDA project in 2010-2015. Of the products, 39% were powders/crystals, 32% tablets/capsules, 16% herbal materials, 8% liquids, 1% blotters, and 4% others. The analysis involved tandem mass spectrometry and nuclear magnetic resonance spectroscopy. In 88 products (35%), classic psychoactive substances, prescription pharmaceuticals, dietary supplements, or doping agents were found; however, in none of these cases had an NPS-related intoxication been indicated from product markings or patient self-reports. Another 12 products tested negative for psychoactive substances. The remaining 151 products contained 86 different NPS (30% contained ≥2 substances). In 104 drug products, a specific NPS ingredient was indicated based on labelling (69%) or patient self-report; in 92 cases this was also analytically confirmed to be correct. Overall, the NPS products submitted for analysis in the STRIDA project showed a high degree of consistency between suspected and actual content (88%). The results of related urine and/or blood analysis further demonstrated that the patients commonly (89%) tested positive for the indicated NPS, but also revealed that polysubstance intoxication was common (83%), indicating use of additional drug products.

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“…This diagnosis is also recognized by the National Association of Medical Examiners and used by medical examiners. Excited delirium is often associated with cocaine toxicity and can be associated with synthetic cannabinoids and bath salts [54–56]. There is no standardized well accepted treatment approach to these patients.…”

Section: Resultsmentioning

confidence: 99%

“…Prolactin levels are not increased in these patients. Seizures could develop in subjects without known epilepsy secondary to drug toxicity, and their detection during sustained physical confrontations, especially if akinetic, might be quite difficult [54, 55]. …”

Section: Resultsmentioning

confidence: 99%

Comprehensive Histological and Immunochemical Forensic Studies in Deaths Occurring in Custody

Nugent

Orellana-Barrios²,

Buscemi

2017

International Scholarly Research Notices

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In-custody deaths have several causes, and these include homicide, suicide, natural death from chronic diseases, and unexplained death possibly related to acute stress, asphyxia, excited delirium, and drug intoxication. In some instances, these deaths are attributed to undefined accidents and natural causes even though there is no obvious natural cause apparent after investigation. Understanding these deaths requires a comprehensive investigation, including documentation of circumstances surrounding the death, review of past medical history, drug and toxicology screens, and a forensic autopsy. These autopsies may not always clearly explain the death and reveal only nonspecific terminal events, such as pulmonary edema or cerebral edema. There are useful histologic and biochemical signatures which identify asphyxia, stress cardiomyopathy, and excited delirium. Identifying these causes of death requires semiquantitative morphologic and biochemical studies. We have reviewed recent Bureau of Justice Statistics on in-custody death, case series, and morphological and biochemical studies relevant to asphyxia, stress cardiomyopathy, and excited delirium and have summarized this information. We suggest that regional centers should manage the investigation of these deaths to provide more comprehensive studies and to enhance the expertise of forensic pathologists who would routinely manage potentially complex and difficult cases.

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An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA

Cited by 66 publications

References 10 publications

Functional evaluation of carboxy metabolites of synthetic cannabinoid receptor agonists featuring scaffolds based on L‐valine or L‐tert‐leucine

Functional evaluation of carboxy metabolites of synthetic cannabinoid receptor agonists featuring scaffolds based on L‐valine or L‐tert‐leucine

Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances

Comprehensive Histological and Immunochemical Forensic Studies in Deaths Occurring in Custody

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