Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Second, we could not adb butinaca retrieve further detailed information about the e-cigarette that was used by the patient such as the label or the region of origin. Whether a recreational drug can be administered via vaping, depends on whether the drug becomes volatile under the evaporation temperature of the e-cigarette. Of these samples, 22 contained one or more SCRAs, THC was only detected in 11 samples, only one contained cannabidiol and 6 contained a mixture of THC and cannabidiol. There is difficulty in finding the right information about the NPS, defining their potency and confirmation of their existence in e-liquids or urine samples.
Data availabili

A limitation of this case report is that we did not have a urine sample available for additional NPS testing. Point-of-care DOA tests using urine to screen for misuse of multiple substances, regularly include cannabis, amphetamines, cocaine, opioids, benzodiazepines and methadone. THC, methamphetamine, SRCA, lysergic acid diethylamide (LSD), gamma-hydroxybutyrate (GHB) and ketamine are likely to become volatile under the temperature of current e-cigarettes, while crack cocaine is hard to vaporise. A systematic review including data of 114 patients of which the majority was intoxicated due to SCRA smoking revealed that 45 % of the patients who present at the ER after an intoxication due to SCRA smoking recovered within 24 hours

The current study indicates that the test compounds produce locomotor depression similar to that of Δ9-THC, and fully substitute for the discriminative stimulus effects of Δ9-THC. In summary, these 5F-MDMB-PINACA, MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA have similar abuse liability as Δ9-tetrahydrocannabinol and should be controlled in a similar fashion. Much of the in vivo adb butinaca testing of the synthetic cannabinoid compounds have been pre-clinical studies focused on their cannabinoid-like effects or like the present study, focused on their abuse liability. There is indication that at least some of the first-generation synthetic cannabinoids act at receptors other than cannabinoid CB1 and CB2 (Wiley et al., 2016), and a compound from the present study, 5F-MDMB-PINACA, was found to activate midbrain dopamine neurons, but not serotonin neurons (Asaoka et al., 2016

The same procedure was then applied to the mice once every day for 5 days. It was considered as coordination disturbance when mice fell from the test apparatus within 2 min. Mice that remained their position on the running apparatus at 10 rpm for at least 2 min were selected for further evaluation.
Table of Conten

All of the compounds tested in the present study depressed locomotor activity as is typical for other synthetic cannabinoids (see review by Wiley et al., 2017). Average horizontal activity counts/10 min as a function of time (10 min bins) and dose. Depressant effects of 1.33 mg/kg were observed within 10 min following administration and peak depressant effects were adb butinaca observed between 0–30 min. Duration of the locomotor depression increased over dose from 30 min following 0.1 mg/kg to 2.5 h following 1 mg/k

The chemical structures of the recent synthetic cannabinoids are unlike that of Δ9-THC, but are largely based on the structure of older synthetic cannabinoids that are known to have substantial abuse liability (Fig. 1

LC separates the urine or blood sample and QTOF-MS provides high-resolution and accurate mass measurements for precise identification and structural elucidation of compounds. The LC-QTOF-MS method offers a more comprehensive and sensitive approach for drug detection, covering hundreds of recreational drugs, including NPS. Besides increasing the temperature to enlarge the drug aerolisation and bioavailability, one can elevate the flow rate of air through the e-cigarette and/or add a diluent . Of all e-cigarette users registered at this forum, 7.8 % vaped SCRAs . About 15 % of individuals registered at forums for drug users such as erowid.org who vaped cannabis have also vaped SRCAs. SCRAs belong, together with synthetic opioids, cathinones, amphetamines and hallucinogens to the new psychoactive substances (NPS) that are currently developed at high speed.
Data availabili

Due to the unknown toxicity of newly emerging SCRAs, forensic assessments of cases involving these substances are challenging. According to the reported cases and reviews of the scientific literature, concurrent ethanol consumption should amplify the toxicity of SCRAs. The concentration of 4F-MDMB-BINACA in the postmortem blood was 2.50 and 2.34 ng/mL, and blood alcohol concentration was 2.11 and 2.49 g/L, respectively. Two fatal cases are reported caused by simultaneous consumption of 4F-MDMB-BINACA and ethanol.
Fig. 2.
4F-MDMB-BINACA was hydrolysed via ester hydrolysis forming the 4F-MDMB-BINACA ester hydrolysis metabolite (B22). Data obtained from the twenty urine samples were retrospectively analysed and processed using TraceFinder software based on the identification criteria of mass errors less than ± 5 ppm for full MS peaks and MS/MS peaks from the theoretical mass and matching of MS/MS spectra. The mixture was vortex-mixed and 500 µL of this mixture and 500 µL of methanol were loaded onto the Clean Screen FASt® tube. After incubation, the mixture was cooled at room temperature, and 150 µL of purified water was added. High-resolution QTOF-MS data were acquired on an Agilent 6510 Accurate Mass QTOF mass spectrometer (Agilent Technologies) equipped with dual electrospray ionization (ESI) source operated in both positive and negative ion modes, to determine accurate masses of the metabolites. Chromatographic separation was performed on an Agilent 1290 LC system with a Poroshell 120 EC-C18 analytical column (2.7 μm, 75 × 2.1 mm; Agilent Technologies, Santa Clara, CA, USA).
Fig. 1.
Monitoring metabolism of synthetic cannabinoid 4F-MDMB-BINACA via high-resolution mass spectrometry assessed in cultured hepatoma cell line, fungus, adb butinaca liver microsomes and confirmed using urine samples The threshold for fatal overdose of combined use of SCRAs and ethanol can be estimated as a little ng/mL (0.37–4.1 ng/mL according to the reported cases) of SCRA and 1.5–2.5 g/L of ethanol. The reported cases and reviews of the scientific literature suggest a possible synergistic effect between SCRAs and ethanol, because their combined use clearly increases their toxicity. The victim died due to severe necrotizing pancreatitis and acute kidney injury evolving into multi-organ failure 11 days after hospital admission . Studies have found no unequivocal synergistic effect between THC and ethanol at low or moderate ethanol doses [29, 30], but no data on high doses of ethanol are available. Given that THC and ethanol act on the same receptors, data on their simultaneous use may yield important insights in this regard.
Fungus C. elegans
Concentrations of 4F-MDMB-BINACA in the postmortem blood samples were 2.50 and 2.34 ng/mL, which are in line with published data. Although the lethal dose of 4F-MDMB-BINACA is unknown, its concentration in postmortem blood samples was found to range between 0.10 and 2.90 ng/mL . In SCRA-related cases in which the deceased suffered from heart disease, the SCRA concentration in the postmortem blood was less than 1 ng/mL . Concentrations of SCRAs in postmortem cases cover a wide range ; however, some reports of survival have also been published—even at relatively high blood SCRA concentrations [19, 20