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Four deaths that seemed to have been caused by a designer drug occurred within a 3-week period in Sendai, Japan. In each case, the decedent possessed the same sachet, labeled "Heart Shot BLACK", which contained a dried plant material with an aromatic scent. It was revealed in our analysis that the product contained a synthetic cannabinoid receptor agonist, 5-fluoro ADB (methyl 2-[1-(5-fluoropentyl)-1H-indazole-3-carboxamide]-3,3-dimethylbutanoate, also known as 5-fluoro MDMB-PINACA), which is now classified as a restricted designer drug in Japan after it caused several casualties. For standard samples, the detection of 5-fluoro ADB in whole blood in the calibration range (0.04-4 ng/mL) was successful with recoveries of 94.6-98.1%, limits of detection of 6 pg/mL, and limits of quantification of 40 pg/mL. The intraday and interday precisions were 0.9-4.8% and 1.1-6.6%, respectively. The bias was -1.1 to 2.9%. We were able to confirm that 5-fluoro ADB was present in the blood of all four decedents at a concentration of 0.11-1.92 ng/mL. From the autopsy, toxicological findings, and circumstances surrounding the cases, it was considered that inhalation of 5-fluoro ADB could have contributed to the deaths. However, the extent to which 5-fluoro ADB contributed to the deaths remains unclear due to the current lack of toxicological information on the compound. In future research, the toxicity of 5-fluoro ADB in humans and the mechanism underlying this effect need to be elucidated.

Objective We conducted a retrospective study on the epidemiological and clinical features of patients with acute caffeine poisoning in Japan. Methods Letters requesting participation were sent to 264 emergency departments of hospitals, and questionnaires were mailed to those that agreed to participate. Patients Participants were patients transported to emergency departments of hospitals between April 2011 and March 2016 after consuming large or massive amounts of caffeinated supplements and/or energy drinks (caffeine dose ≥1.0 g). Results We surveyed 101 patients from 38 emergency departments. Since April 2013, the number of patients has markedly increased. Of these young patients (median age, 25 years), 53 were men, and 97 had consumed caffeine in tablet form. Estimated caffeine doses (n=93) ranged from 1.2 to 82.6 g (median, 7.2 g). Serum caffeine levels on admission (n=17) ranged from 2.0 to 530.0 μg/mL (median level, 106.0 μg/mL). Common abnormal vital signs and laboratory data on admission included tachypnea, tachycardia, depressed consciousness, hypercreatinekinasemia, hyperglycemia, hypokalemia, hypophosphatemia, and hyperlactatemia. Common signs and symptoms in the clinical course included nausea, vomiting, excitement/agitation, and sinus tachycardia. Seven patients (6.9%) who had consumed ≥6.0 g of caffeine, or whose serum caffeine levels on admission were ≥200 μg/mL, developed cardiac arrest. Ninety-seven patients (96.0%) recovered completely, but 3 patients (3.0%) died. Conclusion The present analysis of data from more than 100 emergency patients revealed clinical features of moderate to fatal caffeine poisoning. We recommend highlighting the toxicity risks associated with ingesting highly caffeinated tablets.

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Aim:Reporting of the analytical and clinical findings of synthetic cannabinoids and cathinones is essential in carrying out a complete clinical assessment of new psychoactive substances. Methods:From 2012 to 2014, we examined synthetic cathinone and cannabinoid poisoning in six patients aged 22-42 years old.Analyses of these compounds were carried out using liquid chromatography-tandem mass spectrometry. Results:The observed clinical symptoms were similar to those reported for intoxication with synthetic cathinones and cannabinoids.In cases of intoxication with synthetic cathinones, the psychiatric and neurological symptoms were long-lasting, and these compounds were detected in serum for 15-48 h after use. Although the clinical symptoms induced by the synthetic cannabinoids disappeared within several hours after use, the range of serum concentrations of these compounds was ≤5 ng/mL for 1-3 h after use. In one fatal case, in which high serum concentrations of synthetic cathinones and cannabinoids were detected, the most plausible cause of death was heart failure due to overdose with these drugs. The long-lasting symptoms induced by synthetic cathinones correlated with the long detection window in serum, whereas the early disappearance of symptoms induced by synthetic cannabinoids corresponded to the short detection window in serum.Conclusions: This study shows that the profiles of synthetic cathinones and cannabinoids in serum are closely related to the duration of the toxic symptoms and that concomitant use of two psychoactive drugs with different pharmacological actions may have the potential for fatal cardiotoxicity.

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