Case reportDeath due to diabetic ketoacidosis: Induction by the consumption of synthetic cannabinoids?
Introduction
The internet drug market is flooded with steadily changing synthetic substances being consumed as an alternative to natural cannabis products. Synthetic cannabinoids have been shown to act as full agonists at CB1 receptors with an increased affinity, thus leading to longer duration of effects and an increased likelihood of psychological effects. Those substances reach forensic interest because of possible serious intoxications mainly due to cardiac effects and can lead to death [1], [2], [3], [4]. After the consumption of synthetic cannabinoids both symptoms which are also described after cannabis intoxications (tachycardia, sedation, psychosis, anxiety and panic attacks) and further symptoms like agitation, convulsions, nausea and emesis were detected [5], [6]. In one case a patient suffered from chest pain after the use of K2 which ended in electrocardiogram changes (ST elevation), elevated troponin levels and myocardial infarction in a 16-year old [1]. Another patient died from sudden cardiac arrest after K2 consumption [3]. After the consumption of 5F-PB-22 (in combination with other drugs and alcohol) a young men suffered from severe coagulopathy, acute kidney injury, acute respiratory failure, hypoxaemia, severeanion gap metabolic and lactic acidosis. Cause of death was acute liver failure [2]. Gugelmann described a case of a generalized tonic–clonic seizure after the consumption of PB-22 [4].
Structures of synthetic cannabinoids detected in the presented case are shown in Fig. 1. Already published pharmacological potential of the substances described by their binding affinity and their activation potential of the human cannabinoid receptor types 1 and 2 are described in Table 1. 5F-AKB48 (5F-APINACA) and STS-135 (5F-APICA) are compounds with adamantyl moiety being sold on the internet market [7] and which could be detected in herbal mixtures and blood samples of cases with driving under the influence of drugs all over Europe [8], [9], [10]. UR-144, a substance with tetramethylcyclopropyl group selective for the CB2 receptor was found in bulk material [11] and blood samples [8], [12], [13]. The synthetic cannabinoids JWH-122 and AM-2201 are well known substances synthesized in the beginning of the spice era [14], [15]. MAM2201 and EAM2201 do only differ by the addition of a methyl (MAM2201) or ethyl (MAM2201) moiety in the 4-position of the naphthyl moiety from AM2201. Substances with 1-(aminocarbonyl)-2-methylpropyl] 3-carboxamide moiety are 5F-AMB, AB-FUBINACA and AB-CHMINACA.
Diabetic coma is the most severe form of hyperglycaemic metabolic disorders. The post mortem diagnosis of this disorder of glucose metabolism is difficult and vague due to a lack of characteristic morphological findings. Particularly biochemical measurements have to complement autopsy findings and case history in case of fatal hyperglycaemic dysregulations. Diabetic ketoacidosis is accompanied by high blood glucose levels and the presence of ketone bodies e.g. in blood. Blood glucose – at its maximum at the moment of death – is rapidly metabolized into lactate by glycolysis. Hence, it is not possible to draw important conclusions concerning primary blood glucose levels [19], [20]. Therefore, post mortem biochemical evaluation of glucose metabolism has to be based on a combination of glucose and lactate levels in vitreous humour (VH) or cerebrospinal fluid (CSF) by addition of both concentrations, estimated in milligrams per decilitre [21]. This so called “sum formula of Traub”, especially concerning VH, should be used to diagnose hyperglycemia. High HbA1c and acetone concentrations can help to complete the diagnosis.
We present a diabetic patient who had consumed several synthetic cannabinoids. We offer that the use of these drugs was contributory to the primary cause of death, which was diabetic ketoacidosis. Specifically, the use of these intoxicating substances affected the decedents ability to self-administer the required insulin. To our knowledge it is the first case in which forensic toxicological (synthetic cannabinoids) and biochemical measurements could demonstrate a connection between synthetic cannabinoid use and hyperglycaemia.
Section snippets
Case history
Upon our information, a 25-year-old man was found dead in his apartment. He was lying on his back on the floor of his kitchen. He was known to habitually consume drugs. Next to his couch a self-made bong and a cannabis mill were found (Fig. 2). In the year before his death there had been two ambulance appearances in his house because he had consumed drugs. In both cases, he had consumed the synthetic cannabinoid AB-FUBINACA. Additionally, he was suffering from insulin dependent diabetes. Two
Chemical toxicological analysis
We received the following matrices from autopsy: blood from a femoral vein; heart blood; urine; vitreous humour (VH); and cerebrospinal fluid (CSF). A general unknown screening was performed by immunochemical analysis and GC/MS (Pfleger/Maurer/Weber Library) and LC/MS–MS (Cliquid Library) after solid phase extraction, but did not reveal the presence of drugs generally used.
Since insulin vials were found next to the body, an analysis for human insulin and its synthetic analogues insulin lispro
Autopsy findings
Body of a 25-year-old man, body weight 54.5 kg, height 180 cm Brain oedema, pulmonary oedema. Subepicardial petechial haemorrhaeges. Hepatic steatosis. Narrow ascending aorta (so-called aorta angusta). Small myocardial scars. 150 ml greenish stomach contents with some black particles. Histology: pulmonary congestion and oedema. Microvesicular steatosis of the liver. Armanni–Ebstein cells of the kidneys.
Chemical toxicological analyses
Apart from synthetic cannabinoids no further drugs or medicinal drugs (insulins) could be
Discussion
We present an autopsy case in which diabetic ketoacidosis was determined to be the cause of death.
The deceased had consumed several synthetic cannabinoids prior to his death. Most of the detected substances have been shown to have high affinities to cannabinoid receptors (see Section 1) which lead to an overstimulation of receptors and can lead to severe side effects. As there are only a few studies about detection windows of synthetic cannabinoids in blood and urine after single or habitual
Conclusion
We present a case of a man who suffered from diabetic ketoacidosis probably following the consumption of synthetic cannabinoids. Several cannabinoids could have been detected in post mortem blood while biochemical measurements (elevated sum formula of Traub, elevated HbA1c and elevated acetone concentration in blood) indicated a diabetic ketoacidosis as cause of death. Death due to hyperglycaemia could have been induced by skipping of insulin doses due to his intoxicated state or by the
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2022, Journal of Chromatography ACitation Excerpt :Synthetic cannabinoids are sold as “K2” or “Spice” and these products are easily available in smoke shops or through the internet [3], and they are especially popular among young adults. Compared to THC, synthetic cannabinoids represent a much greater danger [4], with common side effects that can include confusion, dizziness, drowsiness, restlessness, irritability, nausea, vomiting, and chest pain, as well as more serious effects that can lead to death [5–8]. Five synthetic cannabinoids (JWH-019; JWH-073; JWH-200; CP-47,497; and CP-47,497, C8 homologue) were listed by the US Drug Enforcement Administration (DEA) as schedule 1 controlled substances in March 2011 [9].
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2022, Principles of Forensic Pathology: From Investigation to CertificationMono-/polyintoxication with 5F-ADB: A case series
2019, Forensic Science InternationalDeath cases involving certain new psychoactive substances: A review of the literature
2019, Forensic Science InternationalA case of intoxication with a mixture of synthetic cannabinoids EAM-2201, AB-PINACA and AB-FUBINACA, and a synthetic cathinone α-PVP
2018, Legal MedicineCitation Excerpt :As to AB-PINACA, its blood levels were reported to be 32.8 and 12.2 ng/ml in [4] and 42 ng/ml in [5], and its urine level was 23 pg/ml [2]. As to AB-FUBINACA, its blood level was reported to be 0.97 ng/ml in [3], and its urine level, 10 pg/ml in [2]. As to α-PVP, its blood, urine and even tissue levels were reported in several works [6–9].