Forty‐Three Fatalities Involving the Synthetic Cannabinoid, 5‐Fluoro‐<scp>ADB</scp>: Forensic Pathology and Toxicology Implications

Boland, Diane M.; Reidy, Lisa; J, Seither; Radtke, Jay M.; Lew, Emma O.

doi:10.1111/1556-4029.14098

Cited by 29 publications

(19 citation statements)

References 16 publications

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“…Reports on the identification of synthetic cannabinoid metabolites in blood are currently limited, but awareness of the necessity of this practice appears to be increasing. In the instance of 5F‐ADB, multiple reports on the identification of M5 in blood have been published 39–42,45,50 . The authors only found one published report, by Kraemer et al, 43 mentioning the identification of M1 in blood and this did not provide detailed analysis of M1.…”

Section: Resultsmentioning

confidence: 99%

“…In the instance of 5F-ADB, multiple reports on the identification of M5 in blood have been published. [39][40][41][42]45,50 The authors only found one published report, by Kraemer et al, 43 mentioning the identification of M1 in blood and this did not provide detailed analysis of M1. The current report supplements this work, and provides the first detailed report on the presence of M1 in blood in the absence of the parent 5F-ADB compound.…”

Section: Identification Of Predominant Metabolites In Authentic Hummentioning

confidence: 99%

“…A number of toxicology reports from Bulgaria, Germany, Japan, New Zealand, Spain, Turkey, and the United States have included overdose, drowning, driving under the influence of drugs (DUID), and prison inmate fatalities linked to the consumption of 5F-ADB. 27,34,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] Analysis of human biological specimens for the presence of synthetic cannabinoids typically entails identifying the parent drug in blood specimens, and/or its metabolites in urine. 7 However, this approach is incomplete, as many synthetic cannabinoid metabolites have been determined to be pharmacologically active and also appear in blood samples.…”

Section: Introductionmentioning

confidence: 99%

“…5F‐ADB has been implicated in numerous acute toxicity events and fatalities throughout the world. A number of toxicology reports from Bulgaria, Germany, Japan, New Zealand, Spain, Turkey, and the United States have included overdose, drowning, driving under the influence of drugs (DUID), and prison inmate fatalities linked to the consumption of 5F‐ADB 27,34,39–52 …”

Section: Introductionmentioning

confidence: 99%

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Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry

Presley

Castaneto

Logan

et al. 2020

Rapid Comm Mass Spectrometry

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Indazole carboxamide synthetic cannabinoids, a prevalent class of recreational drugs, are a major clinical, forensic and public health challenge. One such compound, 5F-ADB, has been implicated in fatalities worldwide. Understanding its metabolism and distribution facilitates the development of laboratory assays to substantiate its consumption. Synthetic cannabinoid metabolites have been extensively studied in urine; studies identifying metabolites in blood are limited and no data on the metabolic stability (half-life, clearance and extraction ratio) of 5F-ADB have been published prior to this report. Methods: The in vitro metabolism of 5F-ADB was elucidated via incubation with human liver microsomes for 2 h at 37 C. Samples were collected at multiple time points to determine its metabolic stability. Upon identification of metabolites, authentic forensic human blood samples underwent liquid-liquid extraction and were screened for metabolites. Extracts were analyzed via ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS) operated in positive electrospray ionization mode. Results: Seven metabolites were identified including oxidative defluorination (M1); carboxypentyl (M2); monohydroxylation of the fluoropentyl chain (M3.1/M3.2) and indazole ring system (M4); ester hydrolysis (M5); and ester hydrolysis with oxidative defluorination (M6). The half-life (3.1 min), intrinsic clearance (256.2 mL min −1 kg −1), hepatic clearance (18.6 mL min −1 kg −1) and extraction ratio (0.93) were determined for the first time. In blood, M1 was present in each sample as the most abundant substance; two samples contained M5; one contained 5F-ADB, M1 and M5. Conclusions: 5F-ADB is rapidly metabolized in HLM. 5F-ADB, M1 and M5 are pharmacologically active at the cannabinoid receptors (CB 1 /CB 2) and M1 and M5 may contribute to a user's impairment profile. The results demonstrate that it is imperative that synthetic cannabinoid assays screen for pharmacologically active metabolites, especially for drugs with short half-lives. The authors propose that M1 and M5 are appropriate markers to include in laboratory blood tests screening for 5F-ADB.

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Section: Resultsmentioning

confidence: 99%

Section: Identification Of Predominant Metabolites In Authentic Hummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry

Presley

Castaneto

Logan

et al. 2020

Rapid Comm Mass Spectrometry

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“…However, the NPS, especially the synthetic cannabinoids (SC) have gained increasing popularity both in local media and media worldwide. Up to now, a lot of fatalities with SC at least contributing to the occurrence of death have already been reported (Boland et al 2019;Darke et al 2019;Kraemer et al 2019;Yamagishi et al 2018). Besides these single case reports, some systematic and few controlled animal studies have been performed to obtain information about the tissue distribution of SC (Castaneto et al 2015;Meyer 2016).…”

Section: Introductionmentioning

confidence: 99%

Time- and temperature-dependent postmortem concentration changes of the (synthetic) cannabinoids JWH-210, RCS-4, as well as ∆9-tetrahydrocannabinol following pulmonary administration to pigs

et al. 2020

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In forensic toxicology, interpretation of postmortem (PM) drug concentrations might be complicated due to the lack of data concerning drug stability or PM redistribution (PMR). Regarding synthetic cannabinoids (SC), only sparse data are available, which derived from single case reports without any knowledge of dose and time of consumption. Thus, a controlled pig toxicokinetic study allowing for examination of PMR of SC was performed. Twelve pigs received a pulmonary dose of 200 µg/kg BW each of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1pentyl-indole-3-yl)methanone (RCS-4), and Δ9-tetrahydrocannabinol via an ultrasonic nebulizer. Eight hours after, the pigs were put to death with T61 and specimens of relevant tissues and body fluids were collected. Subsequently, the animals were stored at room temperature (n = 6) or 4 °C (n = 6) and further samples were collected after 24, 48, and 72 h each. Concentrations were determined following enzymatic cleavage and solid-phase extraction by liquid-chromatography tandem mass spectrometry applying the standard addition approach. High concentrations of the parent compounds were observed in lung, liver, kidney and bile fluid/duodenum content as well as brain. HO-RCS-4 was the most prevalent metabolite detected in PM specimens. In general, changes of PM concentrations were found in every tissue and body fluid depending on the PM interval as well as storage temperature.

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‘Flying high?’—Jump from a height in a ‘Spice’ high?: A case report on the synthetic cannabinoid 5F‐MDMB‐P7AICA

Walle

Doerr

Schmidt

et al. 2022

Drug Testing and Analysis

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Regarding the high potency of synthetic cannabinoids (SC), many intoxications and fatal cases are reported in literature. Here, we report on a fatality with 5F‐MDMB‐P7AICA contributing to the occurrence of death. A 31‐year‐old man died 10 h after he fell from the rooftop of a house. Police investigations revealed that he had consumed a ‘legal high’ herbal blend some hours earlier. An initial toxicological screening for new psychoactive substances (NPS) was negative. One year after, the analysis of confiscated drug samples revealed the SC 5F‐MDMB‐P7AICA being unknown at the time of the first investigations. Hence, post‐mortem specimens were retrospectively analysed for 5F‐MDMB‐P7AICA and its dimethylbutanoic acid (DBA) metabolite. Lung, liver, kidney and bile fluid (BF) of the decedent were analysed following solid‐phase extraction and standard addition, heart blood (HB) and peripheral blood (PB) by fully validated liquid–liquid extraction and protein precipitation methods. Additionally, hair specimens were analysed to examine a possible chronic consumption of the SC. All specimens were analysed by liquid–chromatography tandem mass spectrometry. 5F‐MDMB‐P7AICA was detected in HB (0.69 ng/ml), PB (1.2 ng/ml) and hair. DBA was found in HB (46 ng/ml) and PB (5.7 ng/ml) and could additionally be identified in liver and kidney (approximately 4–5 ng/g), lung (approximately 12 ng/g) and BF (approximately 60 ng/g). Compared with the parent compound, much higher concentrations of DBA were quantified. This case shows that drugs found at the scene can provide helpful initial information for further toxicological screenings in biological samples, especially when there is evidence of NPS consumption.

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Forty‐Three Fatalities Involving the Synthetic Cannabinoid, 5‐Fluoro‐ADB: Forensic Pathology and Toxicology Implications

Cited by 29 publications

References 16 publications

Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry

Metabolic profiling of synthetic cannabinoid 5F‐ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra‐high‐performance liquid chromatography/high‐resolution mass spectrometry

Time- and temperature-dependent postmortem concentration changes of the (synthetic) cannabinoids JWH-210, RCS-4, as well as ∆9-tetrahydrocannabinol following pulmonary administration to pigs

‘Flying high?’—Jump from a height in a ‘Spice’ high?: A case report on the synthetic cannabinoid 5F‐MDMB‐P7AICA

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