Monitoring Metabolism Of Synthetic Cannabinoid 4F-MDMB-BINACA Via High-resolution Mass Spectrometry Assessed In Cultured Hepatoma Cell Line, Fungus, Liver Microsomes And Confirmed Using Urine Samples Forensic Toxicology Springer Nature Link

The current study indicates that the test compounds produce locomotor depression similar to that of Δ9-THC, and fully substitute for the discriminative stimulus effects of Δ9-THC. In summary, these 5F-MDMB-PINACA, MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA have similar abuse liability as Δ9-tetrahydrocannabinol and should be controlled in a similar fashion. Much of the in vivo adb butinaca testing of the synthetic cannabinoid compounds have been pre-clinical studies focused on their cannabinoid-like effects or like the present study, focused on their abuse liability. 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

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


Separation of compounds was performed on a 2.1 mm×100 mm, 1.7 adb butinaca μm particle size ACQUITY Torus™ DIOL analytical column (Waters) with guard cartridge. Measurements were performed by an ACQUITY UPC2 supercritical fluid chromatography system (Waters) coupled with a Xevo TQ-S Triple Quadrupole Mass Spectrometer (Waters). During the death scene examination, multiple cigarette butts without filters were found in an ashtray; also found were alcohol bottles, an unopened box of nebivolol-containing drug, and 18 g of unrecognizable herbal residue in a cigarette box.
Victim B also brought "something resembling a drug" (unrecognizable by Witness A) from his cousin (Witness B) in a cigarette box and mixed this substance with their tobacco. The half-maximal effective concentration (EC50) of 4F-MDMB-BINACA is 5.69 nM (2.76–11.0 nM) on CB1, and 0.69 nM (0.30–1.56 nM) on CB2, in vitro half-life (t1/2) is 10.27 min . It is usually available as a powder, liquid (vapor fluid), or herbal plant mixtur


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 adb butinaca 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

4. Drugs
In general, the locomotor depressant and discriminative stimulus effects 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. 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.
Michael B Gatch
Substantial depressant effects were observed within the first 10 min, and maximal depression was observed between 0–30 min following administration. Tremors were observed 30 minutes following 1 mg/kg AMB-FUBINACA in 3 of 8 mice (data not shown). Substantial depressant effects were observed within the first 10 min, and maximal depression was observed between 10–40 min and lasted up to 2.5 to 3 h at the adb butinaca highest dose tested (0.5 mg/kg).
Figure 1.
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). 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 liability. 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.
Michael B Gat