Morris Batchelor demandée il y a 3 heures
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
Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans
This might be due to the low activity of numerous metabolizing enzymes resulting in lower drug biotransformation . HepG2 model detected the major ester hydrolysis metabolite of 4F-MDMB-BINACA in abundance but the rest of the metabolites were found in a small amount. Elegans and HLM models detected all of the in-vivo metabolites (100%), whilst HepG2 cells detected 7 out of the 8 in-vivo metabolites (87.5%). Hence, structural elucidation could not be confirmed unless a reference standard is made availabl
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
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
The same procedure was then applied to the mice once every day for 5 days. It was considered as coordination disturbance when mice fell from the test apparatus within 2 min. Mice that remained their position on the running apparatus at 10 rpm for at least 2 min were selected for further evaluation.
Table of Conten
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 JWH-210 powder 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
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