Figure 1.
Each training session lasted a maximum of 10 min, and the rats could earn up to 20 food pellets. Thirty minutes prior to the training sessions, rats received an injection of either vehicle or Δ9-THC and were subsequently placed in the behavior-testing chambers, where food (45-mg food pellets; Bio-Serve, Frenchtown, NJ) was available as a reinforcer for every ten responses (FR10) on a designated injection appropriate lever. A houselight was centered over the hopper close to the ceiling and was illuminated only when the levers were active. Each dose range included doses that were without effect to those producing at least 50% depression compared to vehicle control. Twenty-four male Sprague-Dawley rats were obtained from Envigo (Houston, TX). Male ND4 Swiss–Webster mice were obtained from Envigo (Houston, TX) at approximately 8 weeks of age and maintained in the University of North Texas Health Science Center (UNTHSC) animal facility for two weeks prior to testin
As previously mentioned, all of the compounds tested in the present study (MDMB-PINACA, MDMB-CHMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA) act as agonists at CB1 receptors (Banister et al., 2015, 2016; Gamage et al., 2018), which suggests these compounds will produce Δ9-THC-like effects, including abuse liabilit
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
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
Observation item 1st injection 2nd injection 3rd injection 4th injection 5th injection Con. All groups treated with tested synthetic cannabinoids showed decreased weight gain rate in a dose-dependent manner. A total of 5 mice in the JWH-081 (5 mg/kg, i.p.) treated group and 6 mice in the adb butinaca JWH-210 (5 mg/kg, i.p.) treated group showed loss of traction, of which 4 and 5 showed tremor, respectively. Memory retention was measured after the memory acquisition was tested as a probe trial.
About Powder JWH-2
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
Each training session lasted a maximum of 10 min, and the rats could earn up to 20 food pellets. Thirty minutes prior to the training sessions, rats received an injection of either vehicle or Δ9-THC and were subsequently placed in the behavior-testing chambers, where food (45-mg food pellets; Bio-Serve, Frenchtown, NJ) was available as a reinforcer for every ten responses (FR10) on a designated injection appropriate lever. A houselight was centered over the hopper close to the ceiling and was illuminated only when the levers were active. Each dose range included doses that were without effect to those producing at least 50% depression compared to vehicle control. Twenty-four male Sprague-Dawley rats were obtained from Envigo (Houston, TX). Male ND4 Swiss–Webster mice were obtained from Envigo (Houston, TX) at approximately 8 weeks of age and maintained in the University of North Texas Health Science Center (UNTHSC) animal facility for two weeks prior to testin
As previously mentioned, all of the compounds tested in the present study (MDMB-PINACA, MDMB-CHMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA) act as agonists at CB1 receptors (Banister et al., 2015, 2016; Gamage et al., 2018), which suggests these compounds will produce Δ9-THC-like effects, including abuse liabilit
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
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
Observation item 1st injection 2nd injection 3rd injection 4th injection 5th injection Con. All groups treated with tested synthetic cannabinoids showed decreased weight gain rate in a dose-dependent manner. A total of 5 mice in the JWH-081 (5 mg/kg, i.p.) treated group and 6 mice in the adb butinaca JWH-210 (5 mg/kg, i.p.) treated group showed loss of traction, of which 4 and 5 showed tremor, respectively. Memory retention was measured after the memory acquisition was tested as a probe trial.
About Powder JWH-2
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