High resolution mass spectrometry such as LC-QTOF-MS allows the detection and identification of a broad spectrum of recreational drugs, including new psychoactive substances. A point-of-care drugs of abuse (DOA) test was initially performed on the urine of the patient. He confirmed drinking 750 ml energy drink without any further consumption of food and using an e-cigarette from Gaziantep, Turkey 10 seconds before the onset of his first symptoms. He usually smokes a pack of cigarettes a day and sometimes smokes e-cigarettes. Combined with non-specific, transient symptoms, clinical recognition of SCRA intoxication is challenging .
Data availability
The intensity is plotted against the retention time for both chromatograms, demonstrating the JWH-210 powder presence and elution profiles of nicotine and ADB-BUTINACA in the analysed vape liquid sample. LC-QTOF-MS Chromatograms of Nicotine (Top) and ADB-BUTINACA (Bottom) in the Vape Liquid used by the patient. The LC-QTOF-MS analysis showed that the e-liquid contained nicotine and ADB-BUTINACA (Fig. 1). Because the point-of-care DOA test is generally not able to detect synthetic recreational drug substances, the liquid of the e-cigarette was thereafter screened using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) on the Waters™ Xevo G3 QTOF MS system. After eating a light meal and drinking caffeinated sports drinks at the ER, the nausea complaints of the patient were reduced and the patient was discharged hom
In-vitro metabolism studies are generally used to complement these data using perfused organs, tissue or cell cultures and microsomal preparations amongst which pooled human liver microsomes (HLM) have been frequently used to elucidate metabolism of SCBs [12,13,14,15,16
Locomotor activity in mice was tested to screen for locomotor depressant effects and to identify behaviorally-active dose ranges and times of peak effect. Previous studies have demonstrated that these compounds have chemical structures similar to synthetic cannabinoids known to have substantial abuse liability and act at the CB1 receptor. Tremors were not observed following AMB-FUBINACA during the drug discrimination study, but the maximum dose tested was only 0.1 mg/kg, which is 10-fold lower than the dose that produced tremors in the mice. AMB-FUBINACA has been implicated in severe adverse effects in recreational users (Adams et al., 2017; Hamilton et al., 2017), which suggests that the range between behaviorally active and toxic doses of AMB-FUBINACA is narrow. Following that line of reasoning, it should also be noted that some of the more recent compounds produced non-linear dose-effect curves and one compound produced an inverted U-shaped dose-effect, such that intermediate dose fully substituted, but higher doses did not (Gatch and Forster, 2018). All of the compounds identified as available on the recreational market and submitted to our laboratory by the US Drug Enforcement Agency for testing have fully substituted at some dose (Gatch and Forster 2014, 2015, 2016, 2018); however; it is important to note that not all structural congeners are active (Wiley et al., 2012
Synthetic cannabinoids have consistently been shown to produce discriminative stimulus effects similar to those JWH-210 powder of Δ9-THC (Bannister and Connor, 2018), and MDMB-FUBINACA fully substituted for Δ9-THC (Gamage et al., 2018). 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). All 5 compounds decreased locomotor activity and produced discriminative stimulus effects similar to those of Δ9-THC, which suggests they may have abuse liability similar to that of Δ9-THC. Subsequent testing identified 5F-ADB to have been present in a total of ten people who had died from unexplained drug overdoses in Japan between September 2014 and December 2014. AMB-FUBINACA produced tremors and may be of increased risk in human recreational users.
Michael B Gatch
These findings are in agreement with earlier studies showing the synthetic cannabinoids substitute for the discriminative stimulus effects of Δ9-THC (see review by Wiley et al., 2017). Pretreatment times and dose ranges for the drug discrimination assay were selected based on the time of peak depression in the locomotor activity assay in mice. As mentioned previously, short-onset compounds have a greater abuse liability; further, compounds that have fewer adverse effects while they are active are likely to be preferred. All five of the compounds in the present study fully substituted with a pretreatment time of 15 min, suggesting a rapid onset of the discriminative stimulus effects. All of the cathinones fully substituted for the discriminative stimulus effects of Δ9-tetrahydrocannabinol (≥80% drug-appropriate responding). Because response suppression may compromise stimulus control, rats failing to complete at least ten responses during the test session were excluded from the analysis of the discriminative stimulus effects of that dose of test compoun
Data availability
The intensity is plotted against the retention time for both chromatograms, demonstrating the JWH-210 powder presence and elution profiles of nicotine and ADB-BUTINACA in the analysed vape liquid sample. LC-QTOF-MS Chromatograms of Nicotine (Top) and ADB-BUTINACA (Bottom) in the Vape Liquid used by the patient. The LC-QTOF-MS analysis showed that the e-liquid contained nicotine and ADB-BUTINACA (Fig. 1). Because the point-of-care DOA test is generally not able to detect synthetic recreational drug substances, the liquid of the e-cigarette was thereafter screened using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) on the Waters™ Xevo G3 QTOF MS system. After eating a light meal and drinking caffeinated sports drinks at the ER, the nausea complaints of the patient were reduced and the patient was discharged hom
In-vitro metabolism studies are generally used to complement these data using perfused organs, tissue or cell cultures and microsomal preparations amongst which pooled human liver microsomes (HLM) have been frequently used to elucidate metabolism of SCBs [12,13,14,15,16
Locomotor activity in mice was tested to screen for locomotor depressant effects and to identify behaviorally-active dose ranges and times of peak effect. Previous studies have demonstrated that these compounds have chemical structures similar to synthetic cannabinoids known to have substantial abuse liability and act at the CB1 receptor. Tremors were not observed following AMB-FUBINACA during the drug discrimination study, but the maximum dose tested was only 0.1 mg/kg, which is 10-fold lower than the dose that produced tremors in the mice. AMB-FUBINACA has been implicated in severe adverse effects in recreational users (Adams et al., 2017; Hamilton et al., 2017), which suggests that the range between behaviorally active and toxic doses of AMB-FUBINACA is narrow. Following that line of reasoning, it should also be noted that some of the more recent compounds produced non-linear dose-effect curves and one compound produced an inverted U-shaped dose-effect, such that intermediate dose fully substituted, but higher doses did not (Gatch and Forster, 2018). All of the compounds identified as available on the recreational market and submitted to our laboratory by the US Drug Enforcement Agency for testing have fully substituted at some dose (Gatch and Forster 2014, 2015, 2016, 2018); however; it is important to note that not all structural congeners are active (Wiley et al., 2012
Synthetic cannabinoids have consistently been shown to produce discriminative stimulus effects similar to those JWH-210 powder of Δ9-THC (Bannister and Connor, 2018), and MDMB-FUBINACA fully substituted for Δ9-THC (Gamage et al., 2018). 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). All 5 compounds decreased locomotor activity and produced discriminative stimulus effects similar to those of Δ9-THC, which suggests they may have abuse liability similar to that of Δ9-THC. Subsequent testing identified 5F-ADB to have been present in a total of ten people who had died from unexplained drug overdoses in Japan between September 2014 and December 2014. AMB-FUBINACA produced tremors and may be of increased risk in human recreational users.
Michael B Gatch
These findings are in agreement with earlier studies showing the synthetic cannabinoids substitute for the discriminative stimulus effects of Δ9-THC (see review by Wiley et al., 2017). Pretreatment times and dose ranges for the drug discrimination assay were selected based on the time of peak depression in the locomotor activity assay in mice. As mentioned previously, short-onset compounds have a greater abuse liability; further, compounds that have fewer adverse effects while they are active are likely to be preferred. All five of the compounds in the present study fully substituted with a pretreatment time of 15 min, suggesting a rapid onset of the discriminative stimulus effects. All of the cathinones fully substituted for the discriminative stimulus effects of Δ9-tetrahydrocannabinol (≥80% drug-appropriate responding). Because response suppression may compromise stimulus control, rats failing to complete at least ten responses during the test session were excluded from the analysis of the discriminative stimulus effects of that dose of test compoun