Death due to diabetic ketoacidosis: Induction by the consumption of synthetic cannabinoids?

Heß, Cornelius; Stockhausen, Simon; Kernbach-Wighton, G.; Madea, Burkhard

doi:10.1016/j.forsciint.2015.08.012

Cited by 88 publications

(30 citation statements)

References 34 publications

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“…Whilst this could be a symptom of generally poor self-care among drug users, it is an interesting finding as previous studies have linked the ingestion of synthetic cannabinoids to hyperglycaemia 18,19 .…”

Section: Discussionmentioning

confidence: 95%

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Seywright

Torrance

Wylie

et al. 2016

Clinical Toxicology

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Clinical Toxicology, 54(8), pp. 632-637. (doi:10.1080Toxicology, 54(8), pp. 632-637. (doi:10. /15563650.2016 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/119581/ Context: MDMB-CHMICA is a synthetic cannabinoid receptor agonist which has caused concern due to its presence in cases of adverse reaction and death. Method: 43 cases of suspected synthetic cannabinoid ingestion were identified from patients presenting at an Emergency Department and from post-mortem casework. These were subjected to liquid-liquid extraction using tertiary-butyl methyl ether and quantitatively this sample. However, the potential for harm associated with low concentrations of MDMB-CHMICA and the symptoms of toxicity being non-specific was highlighted.

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Section: Discussionmentioning

confidence: 95%

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Seywright

Torrance

Wylie

et al. 2016

Clinical Toxicology

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“…However, single-use cannabinoid antagonist therapy to block potentially life-threatening, cannabinoid intoxication may be worth the re-manufacture and testing for such an indication. Although intoxication and possibly deaths (Hess et al, 2015;Lusher, 2016) may be related to cannabinoid receptor agonism, as the causative agents are unlicensed, lack proper toxicology testing and have variable content, these deaths may relate to the actions of toxic metabolites on alternative targets unrelated to the cannabinoid system or possibly non-cannabinoid compounds. The physical effects usually reported include tachycardia, nausea, somnolence, hallucinations, paranoia and dry mouth syndrome (xerostomia) typical of cannabis intoxication.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, synthetic CB 1 receptor agonists, which often exhibit markedly higher agonist activity than THC (K i = 40 nM, at CB 1 receptors; Howlett et al, 2002), have become increasingly widely used as an alternative to botanical cannabis (Keyes et al, 2016). These recreational drugs, such as Spice, Black Mamba and Buzz are laced with a variety of ever-changing, synthetic CB 1 receptor agonists (Fattore and Fratta, 2011;Hutter et al, 2012;Hess et al, 2015;Kemp et al, 2016;Tournebize et al, 2017). These agonists include JWH-018 (K i = 9 nM), JWH-122 (K i = 1 nM), JWH-250 (K i = 11 nM), JWH-251 (K i = 29 nM) and AM2201 (K i = 1 nM), which can cause substantial intoxication, withdrawal symptoms, psychosis and death (Fattore and Fratta, 2011;Kemp et al, 2016;Tournebize et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Antidote to cannabinoid intoxication: the CB₁ receptor inverse agonist, AM251, reverses hypothermic effects of the CB₁ receptor agonist, CB‐13, in mice

Pryce

Baker

2017

British J Pharmacology

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BACKGROUND AND PURPOSECannabis is a recreational drug leading to intoxication, following stimulation of cannabinoid CB 1 receptors. However, more recently, herbs mixed with synthetic cannabinoids sometimes known as 'Spice' and 'Black Mamba' have been increasingly used, and their high CB 1 receptor affinity has led not only to marked intoxication but also life-threatening complications and an increasing number of deaths. Although many studies have indicated that prophylactic treatment with CB 1 receptor antagonists can block cannabimimetic effects in animals and humans, the aim of this study was to determine whether CB 1 receptor antagonism could reverse physical cannabimimetic effects. EXPERIMENTAL APPROACHCannabimimetic effects, measured by the hypothermic response following sedation and hypomotility, were induced by the synthetic CB 1 receptor agonist CB-13 (1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone) in Biozzi Antibody High mice. The CB 1 receptor antagonist/inverse agonist AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) was administered 20 min after the injection of CB-13 and its effects on the cannabimimetic responses were assessed. KEY RESULTSIn this study, the CNS-related cannabimimetic effects, as measured by the hypothermic effect, induced by the CB 1 receptor agonist were therapeutically treated and were rapidly reversed by the CB 1 receptor antagonist/inverse agonist. There was also a subjective reversal of visually evident sedation. CONCLUSIONS AND IMPLICATIONSCannabinoid receptor antagonists have been widely used and so may provide an acceptable single-dose antidote to cannabinoid intoxication. This use may save human life, where the life-threatening effects are mediated by cannabinoid receptors and not offtarget influences of the synthetic cannabinoids or non-cannabinoids within the recreational drug mixture. In animals, cannabimimetic effects have been associated with a tetrad of behavioural effects including catalepsy, analgesia, lack of locomotor activity and thermoregulation, mediated mainly by THC within cannabis and by CB 1 receptors expressed within the CNS (Zimmer et al., 1999;Varvel et al., 2005;Croxford et al., 2008). These behavioural effects induced by THC and synthetic cannabinoids can be blocked by CB 1 receptor antagonists (Varvel et al., 2005;Marshell et al., 2014). Likewise, behavioural and physiological effects of cannabis can be blocked by CB 1 receptor antagonists/inverse agonists in humans (Huestis et al., 2007). Therefore, receptor blockade could act as an antidote to limit potentially life-threatening intoxication.Although there are claims that inverse agonists of CB 1 receptors can reverse cannabimimetic effects of synthetic cannabinoids (Taffe et al., 2015), on closer analysis, it is evident that these antagonists/inverse agonists are typically applied before the cannabinoid agonist. Therefore, it is an inhibition of the development of cannabimimetic effects rather than a reversal of established cannabimimet...

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“…In the first case in Japan, 5F‐AMB, AB‐CHIMINACA and diphenidine were identified in postmortem adipose tissue . In the second German case, 5F‐AMB was found in femoral blood along with AB‐CHIMINACA, AB‐FUBINACA, 5F‐AB‐PINACA, STS135 and THJ2201 . 5F‐AMB is scheduled as an illicit drug in China, Germany, Japan and Singapore .…”

mentioning

confidence: 99%

“…[6] In the second German case, 5F-AMB was found in femoral blood along with AB-CHIMINACA, AB-FUBINACA, 5F-AB-PINACA, STS135 and THJ2201. [7] 5F-AMB is scheduled as an illicit drug in China, Germany, Japan and Singapore. [8][9][10][11] AMB is scheduled in Japan.…”

mentioning

confidence: 99%

Metabolic profiling of new synthetic cannabinoids AMB and 5F‐AMB by human hepatocyte and liver microsome incubations and high‐resolution mass spectrometry

Andersson

Diao

Wohlfarth

et al. 2016

Rapid Comm Mass Spectrometry

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For the first time, AMB and 5F-AMB metabolism profiles were characterized, providing valuable data for identifying these two novel psychoactive substances. The difficulties of differentiating AMB and 5F-AMB from AB-PINACA/5F-AB-PINACA metabolites also were examined. These data improve the interpretation of urinary markers after AMB and 5F-AMB intake. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.

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Death due to diabetic ketoacidosis: Induction by the consumption of synthetic cannabinoids?

Cited by 88 publications

References 34 publications

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Antidote to cannabinoid intoxication: the CB₁ receptor inverse agonist, AM251, reverses hypothermic effects of the CB₁ receptor agonist, CB‐13, in mice

Metabolic profiling of new synthetic cannabinoids AMB and 5F‐AMB by human hepatocyte and liver microsome incubations and high‐resolution mass spectrometry

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Death due to diabetic ketoacidosis: Induction by the consumption of synthetic cannabinoids?

Cited by 88 publications

References 34 publications

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Antidote to cannabinoid intoxication: the CB1 receptor inverse agonist, AM251, reverses hypothermic effects of the CB1 receptor agonist, CB‐13, in mice

Metabolic profiling of new synthetic cannabinoids AMB and 5F‐AMB by human hepatocyte and liver microsome incubations and high‐resolution mass spectrometry

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Product

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Antidote to cannabinoid intoxication: the CB₁ receptor inverse agonist, AM251, reverses hypothermic effects of the CB₁ receptor agonist, CB‐13, in mice