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A 30-min period, beginning when maximal depression of locomotor activity first appeared as a function of dose, was used for analysis of dose-response data and calculation of ED50 values. During test sessions, both levers were active, such that ten consecutive responses on either lever led to 4F ADB reinforcement. The substitution tests occurred only if the rats had achieved 85% injection-appropriate responding on the two prior training sessions.
The locomotor activity assay was used to identify approximate time courses and dose ranges of psychoactive effects, which is useful for identifying parameters for drug discrimination experiments and are also predictive of the time course of the psychoactive effects in human users. The purpose of the present study was to assess the abuse liability of 5F-MDMB-PINACA, MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA. Since there is currently no robust measure of the reinforcing/rewarding effects of cannabinoids, drug discrimination is currently the best model for assessing abuse liability of cannabinoids. The findings produce an apparent paradox, since CPP and self-administration predict with high reliability the likelihood that a compound will be abused by humans, and cannabinoids are well-known to produce active drug-seeking in human

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 .
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The intensity is plotted against the retention time for both chromatograms, demonstrating the 4F ADB 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

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 4F ADB 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

LC-QTOF-MS represents a significant advancement in the field of drug detection, offering higher sensitivity, specificity, and a broader spectrum of detectable substances. Despite all negative results in the point-of-care test for recreational drugs, the liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analysis showed that the liquid of the e-cigarette contained ADB-BUTINACA, a synthetic cannabinoid. We report a 27-year-old man who was admitted to the emergency room because of sudden 4F ADB headache, nausea, vertigo, red eyes and palpitations. Synthetic cannabinoids are gaining popularity globally and detection is not commonly availabl

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 metabolite

Product ions detected at m/z 302, 217, and 145 (B2) confirmed that tert-leucine and indazole moieties remained unchanged, leading to the structure elucidation of a hydroxy-functional group at the 4-position of the butyl side chain by oxidative defluorination. The product ion m/z 336 (loss of methyl ester moiety) further confirmed the presence of dihydroxylated metabolites. The precursor ion, m/z 364 (B14, B5/B6) had a loss of 2 Da from m/z 366 indicated further dehydrogenation of the ester hydrolysis plus monohydroxylated metabolites. The presence of the product ion m/z 320, likely formed from a loss of carbon dioxide, indicated monohydroxylation at the tert-leucine in B8 (m/z 219), butyl side chain in B9 (m/z 145) and indazole moiety in B13 (m/z 161). The precursor ion, m/z 350 showed a loss of 14 Da explaining the hydrolysis of methyl ester from 4F-MDMB-BINACA.
Fig. 2.
The precursor ion m/z 396 (B10, B12/B15) was 32 Da higher than the parent drug, 4F-MDMB-BINACA, suggesting the addition of two hydroxy groups. All the below explanations for transformations into metabolites are based on the data shown in Fig. Metabolites were identified according to their precursor ions, product ions, and fragmentation patterns (Fig. 1). Traditional in-vivo metabolism studies to generate human metabolites of drugs relied heavily on the use of whole animal model systems, which are expensive, limited by drug administration amount, influenced by species variation and faced by many ethical issues. Eight in-vivo metabolites tentatively identified were mainly products of ester hydrolysis with or without additional dehydrogenation, N-dealkylation, monohydroxylation and oxidative defluorination with further oxidation to butanoic acid.
Fig. 1.
This outcome was anticipated since CES-mediated hydrolysis is commonly 4F ADB reported as the major metabolic pathway among the SCBs impacting the terminal ester group . Glucosides and sulfate metabolites have been reported with other SCBs where C. From these three samples, sample 2 contained only an ester hydrolysis metabolite (m/z 350). Both ester hydrolysis followed by oxidative defluorination to butanoic acid (B4, m/z 362) and monohydroxylation at tert-leucine moiety (B8, m/z 366) metabolites were found in 16/20 urine samples (Table 2). A In-vitro metabolites observed in common among respective seven most abundant metabolites in b C. The product ion detected at m/z 235, indicating loss of sulfate, confirmed the identity of the sulfation metabolite.
Fungus C. elegans
Methyl (2S)-2-([1-(4-fluorobutyl)-1H-indazole-3-carbonyl]amino)-3,3-dimethylbutanoate (4F-MDMB-BINACA, 4F-MDMB-BUTINACA or 4F-ADB), found in numerous SCB product seizures, has been reported by various law enforcement since 2018 . However, most of the SCBs are full agonists at CB1 and CB2 receptors, having a higher risk of undesirable side effects when compared to THC which is a partial agonist . Synthetic cannabinoids (SCBs) are agonists at cannabinoid receptor type 1 (CB1) and type 2 (CB2), where they elicit their main effect

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