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
Effects of individual doses were compared to the vehicle control value using a priori contrasts. Response-rate data were analyzed by one-way repeated-measure analysis of variance. Percent drug-appropriate responding was shown only if at 5CLADBA least three rats completed the first fixed ratio, whereas all rats are shown for the response rate dat
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 5CLADBA 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
In general, the locomotor depressant and discriminative stimulus effects 5CLADBA have been observed at doses that do not produce adverse effects, although tremors were observed upon handling in mice that received JWH-210 (Gatch et al., 2016), and 5F-AMB produced sustained vocalization and convulsions in rats (Gatch et al., 2018). All of the synthetic cannabinoids tested in the present study fully substituted for the discriminative stimulus effects of Δ9-THC. Subsequently, a one-way analysis of variance was conducted on horizontal activity counts for the 30-min period of maximal effect, and planned comparisons were conducted for each dose against the vehicle control using single degree-of-freedom F tests. A two-way analysis of variance, with dose as a between groups factor and time as a within subject factor, was conducted on horizontal activity counts/10 min interval.
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
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 5CLADBA 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
Effects of individual doses were compared to the vehicle control value using a priori contrasts. Response-rate data were analyzed by one-way repeated-measure analysis of variance. Percent drug-appropriate responding was shown only if at 5CLADBA least three rats completed the first fixed ratio, whereas all rats are shown for the response rate dat
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 5CLADBA 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
In general, the locomotor depressant and discriminative stimulus effects 5CLADBA have been observed at doses that do not produce adverse effects, although tremors were observed upon handling in mice that received JWH-210 (Gatch et al., 2016), and 5F-AMB produced sustained vocalization and convulsions in rats (Gatch et al., 2018). All of the synthetic cannabinoids tested in the present study fully substituted for the discriminative stimulus effects of Δ9-THC. Subsequently, a one-way analysis of variance was conducted on horizontal activity counts for the 30-min period of maximal effect, and planned comparisons were conducted for each dose against the vehicle control using single degree-of-freedom F tests. A two-way analysis of variance, with dose as a between groups factor and time as a within subject factor, was conducted on horizontal activity counts/10 min interval.
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
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 5CLADBA 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