These synthetic cannabinoids act 4F ADB directly at cannabinoid CB1 and CB2 receptors as does Δ9-tetrahydrocannabinol (Δ9-THC) found in marijuana, but have different chemical structures unrelated to Δ9-THC, different metabolism, and often greater toxicity (Fantegrossi et al., 2014). Discriminative stimulus effects were tested in rats trained to discriminate Δ9-tetrahydrocannabinol (3 mg/kg, 30-min pretreatment). 5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liabilit
Synthetic cannabinoids have consistently been shown to produce discriminative stimulus effects similar to those 4F ADB of Δ9-THC (Bannister and Connor, 2018), and MDMB-FUBINACA fully substituted for Δ9-THC (Gamage et al., 2018). The chemical structures of the recent synthetic cannabinoids are unlike that of Δ9-THC, but are largely based on the structure of older synthetic cannabinoids that are known to have substantial abuse liability (Fig. 1). All 5 compounds decreased locomotor activity and produced discriminative stimulus effects similar to those of Δ9-THC, which suggests they may have abuse liability similar to that of Δ9-THC. Subsequent testing identified 5F-ADB to have been present in a total of ten people who had died from unexplained drug overdoses in Japan between September 2014 and December 2014. AMB-FUBINACA produced tremors and may be of increased risk in human recreational users.
Michael B Gatch
Duration of the locomotor depression increased over dose from 30 min following 0.1 mg/kg to 2.5 h following 1 mg/kg. 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 highest dose tested (0.5 mg/kg). Figure 1 shows average horizontal activity counts/10 min as a function of time (0–4 h) and dose of Δ9-TH
§ (3) of the Hungarian act of Forensic Experts (2016.XXIX), the data of the reported case can be utilized freely for scientific and educational purposes without special ethical permission. These results indicate that the simultaneous intoxication of SCRA and ethanol directly and exclusively caused the death of the two victims. The victims did not have any significant diseases that could have contributed to the outcome. Very limited data are available in the scientific literature about the possible effects of the combined consumption of SCRAs and ethanol. Several case reports describe that the presence of a little ng/mL (0.37–4.1) of SCRAs and a high—but not lethal—concentration of ethanol (1.45–2.7 g/L) directly and exclusively contributed to the death of the victim [24–27] (Table 2). The fact that 4F-MDMB-BINACA was not detected in postmortem urine samples is partly explained by the high rate of hepatic metabolism of SCRAs [11, 14, 22], but also suggests that the victims consumed 4F-MDMB-BINACA shortly before their death
Acute kidney damage and even kidney failure have been reported following use of synthetic cannabinoids (Davidson, et al., 2017). One recent study has looked at other mechanisms of action in some of the older synthetic cannabinoids and reported that some produced varying amounts of activity at sites which are related to cardiotoxicity and heart disease (Wiley et al., 2016). It is not known whether the increased toxicity is due only to activation of CB1 cannabinoid receptors more strongly than Δ9-THC or whether these "super-strength" cannabinoids produce effects at other receptors. A major cause of concern is that some of the more recently seen synthetic cannabinoids are more likely to produce extremely toxic effects than the older synthetics (Tai and Fantegrossi, 2017
Figure 1.
These synthetic cannabinoids act directly at cannabinoid CB1 and CB2 receptors as does Δ9-tetrahydrocannabinol (Δ9-THC) found in marijuana, but have different chemical structures unrelated to Δ9-THC, different metabolism, and often greater toxicity (Fantegrossi et al., 2014). Discriminative stimulus effects were tested in rats trained to discriminate Δ9-tetrahydrocannabinol (3 mg/kg, 30-min pretreatment). 5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liabilit
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 4F ADB 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
Synthetic cannabinoids have consistently been shown to produce discriminative stimulus effects similar to those 4F ADB of Δ9-THC (Bannister and Connor, 2018), and MDMB-FUBINACA fully substituted for Δ9-THC (Gamage et al., 2018). The chemical structures of the recent synthetic cannabinoids are unlike that of Δ9-THC, but are largely based on the structure of older synthetic cannabinoids that are known to have substantial abuse liability (Fig. 1). All 5 compounds decreased locomotor activity and produced discriminative stimulus effects similar to those of Δ9-THC, which suggests they may have abuse liability similar to that of Δ9-THC. Subsequent testing identified 5F-ADB to have been present in a total of ten people who had died from unexplained drug overdoses in Japan between September 2014 and December 2014. AMB-FUBINACA produced tremors and may be of increased risk in human recreational users.
Michael B Gatch
Duration of the locomotor depression increased over dose from 30 min following 0.1 mg/kg to 2.5 h following 1 mg/kg. 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 highest dose tested (0.5 mg/kg). Figure 1 shows average horizontal activity counts/10 min as a function of time (0–4 h) and dose of Δ9-TH
§ (3) of the Hungarian act of Forensic Experts (2016.XXIX), the data of the reported case can be utilized freely for scientific and educational purposes without special ethical permission. These results indicate that the simultaneous intoxication of SCRA and ethanol directly and exclusively caused the death of the two victims. The victims did not have any significant diseases that could have contributed to the outcome. Very limited data are available in the scientific literature about the possible effects of the combined consumption of SCRAs and ethanol. Several case reports describe that the presence of a little ng/mL (0.37–4.1) of SCRAs and a high—but not lethal—concentration of ethanol (1.45–2.7 g/L) directly and exclusively contributed to the death of the victim [24–27] (Table 2). The fact that 4F-MDMB-BINACA was not detected in postmortem urine samples is partly explained by the high rate of hepatic metabolism of SCRAs [11, 14, 22], but also suggests that the victims consumed 4F-MDMB-BINACA shortly before their death
Acute kidney damage and even kidney failure have been reported following use of synthetic cannabinoids (Davidson, et al., 2017). One recent study has looked at other mechanisms of action in some of the older synthetic cannabinoids and reported that some produced varying amounts of activity at sites which are related to cardiotoxicity and heart disease (Wiley et al., 2016). It is not known whether the increased toxicity is due only to activation of CB1 cannabinoid receptors more strongly than Δ9-THC or whether these "super-strength" cannabinoids produce effects at other receptors. A major cause of concern is that some of the more recently seen synthetic cannabinoids are more likely to produce extremely toxic effects than the older synthetics (Tai and Fantegrossi, 2017
Figure 1.
These synthetic cannabinoids act directly at cannabinoid CB1 and CB2 receptors as does Δ9-tetrahydrocannabinol (Δ9-THC) found in marijuana, but have different chemical structures unrelated to Δ9-THC, different metabolism, and often greater toxicity (Fantegrossi et al., 2014). Discriminative stimulus effects were tested in rats trained to discriminate Δ9-tetrahydrocannabinol (3 mg/kg, 30-min pretreatment). 5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liabilit
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 4F ADB 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
