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 JWH-210 powder 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
In general, the locomotor depressant and discriminative stimulus effects JWH-210 powder 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
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 mic
Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. It is illegal to sell, distribute, supply, transport or trade the pharmaceutical drug under the Psychoactive Substances Act 2016. The corresponding indole core analogue, 4F-MDMB-BICA (4F-MDMB-BUTICA), has also been widely sold as a designer drug by chemical providers on the internet, first being identified in May 2020. It has been used as an active ingredient in synthetic cannabis products and sold as a designer drug since late 2018. 4F-MDMB-BINACA (also known as MDMB-4F-BINACA using systematic EMCDDA nomenclature or 4F-MDMB-BUTINACA) is an indazole-based synthetic cannabinoid from the indazole-3-carboxamide family.
Fig.
Tremors were observed in mice 30 minutes following 1 mg/kg AMB-FUBINACA in the present study. 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. Average potency of the discriminative stimulus effects of early compounds was 0.81±0.17 mg/kg (Gatch et al., 2014), whereas the potency of a recent set was 0.09±0.03 mg/kg (Gatch et al., 2018), and the potency of the current set is 0.05±0.01 mg/kg. Short-onset, short-acting compounds have a greater abuse liability, and long-acting compounds pose problems of long-acting adverse effects and interactions with other drugs. The duration of action of the synthetic cannabinoids tested using the 8-h protocol have varied widely, with some producing a duration of action no longer than 1 h, others producing a duration of action between 1–2 h, and others lasting more than 2 h. There seems to be a trend of newer synthetic cannabinoids being more potent than earlier compound
When clinical presentation and/or initial DOA testing results are inconclusive, additional testing with LC-QTOF-MS can be valuable and is recommended. SCRAs and other NPS may not be detected by point-of-care DOA tests. In this case, the point-of-care DOA urine screening was not able to detect the synthetic cannabinoid ADB-BUTINAC
4. Drugs
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. 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 humans. Drug discrimination is a well-known animal model of the subjective effects of drugs and correlates well with abuse liability (Young 2009; Horton et al. 2013). Assessment of abuse liability is based on several factors, including chemical structure, pharmacological mechanism of action, and finally, subjective and reinforcing behavioral effects (FDA, 2010; Swedberg, 2013).
Michael B Gat
In general, the locomotor depressant and discriminative stimulus effects JWH-210 powder 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
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 mic
Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. It is illegal to sell, distribute, supply, transport or trade the pharmaceutical drug under the Psychoactive Substances Act 2016. The corresponding indole core analogue, 4F-MDMB-BICA (4F-MDMB-BUTICA), has also been widely sold as a designer drug by chemical providers on the internet, first being identified in May 2020. It has been used as an active ingredient in synthetic cannabis products and sold as a designer drug since late 2018. 4F-MDMB-BINACA (also known as MDMB-4F-BINACA using systematic EMCDDA nomenclature or 4F-MDMB-BUTINACA) is an indazole-based synthetic cannabinoid from the indazole-3-carboxamide family.
Fig.
Tremors were observed in mice 30 minutes following 1 mg/kg AMB-FUBINACA in the present study. 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. Average potency of the discriminative stimulus effects of early compounds was 0.81±0.17 mg/kg (Gatch et al., 2014), whereas the potency of a recent set was 0.09±0.03 mg/kg (Gatch et al., 2018), and the potency of the current set is 0.05±0.01 mg/kg. Short-onset, short-acting compounds have a greater abuse liability, and long-acting compounds pose problems of long-acting adverse effects and interactions with other drugs. The duration of action of the synthetic cannabinoids tested using the 8-h protocol have varied widely, with some producing a duration of action no longer than 1 h, others producing a duration of action between 1–2 h, and others lasting more than 2 h. There seems to be a trend of newer synthetic cannabinoids being more potent than earlier compound
When clinical presentation and/or initial DOA testing results are inconclusive, additional testing with LC-QTOF-MS can be valuable and is recommended. SCRAs and other NPS may not be detected by point-of-care DOA tests. In this case, the point-of-care DOA urine screening was not able to detect the synthetic cannabinoid ADB-BUTINAC
4. Drugs
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. 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 humans. Drug discrimination is a well-known animal model of the subjective effects of drugs and correlates well with abuse liability (Young 2009; Horton et al. 2013). Assessment of abuse liability is based on several factors, including chemical structure, pharmacological mechanism of action, and finally, subjective and reinforcing behavioral effects (FDA, 2010; Swedberg, 2013).
Michael B Gat