Abuse Potential of Synthetic Cannabinoids: AM-1248, CB-13, and PB-22

Abstract

Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects. The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.

Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents

“…This is consistent with previous studies showing that addictive SCBs, such as JWH-018 and WIN 55,212-2, support IVSA [22,23]. In addition, Mepirapim treatment-induced impulsive behaviours identified by multiple inactive lever presses, which are also induced by other SCBs treatment [20]. These impulsive behaviours are frequently observed in SCB users and are considered to increase the risk of recreational abuse of the drug [24].…”

“…These results indicate that Mepirapim is an addictive drug with reinforcing effects [19]. Furthermore, the average number of inactive lever presses was significantly higher in the Mepirapim groups (0.01 and 0.03 mg•kg −1 •inf −1 ) than in the vehicle group (Figure 2D, F (3,16) = 3.8, p < 0.05), indicating that Mepirapim induces impulsive behaviours similar to those induced by treatment with other SCBs [20]. Two-way ANOVA revealed statistically significant effects from drug treatment (F (3,16) = 3.8, p < 0.05) and day (F (6,96) = 3.58, p < 0.05), but no significant effect of their interaction was observed (F (18,96) = 0.81, p = 0.69).…”

Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression

“…Cryab KO mice exhibited potentially higher sensitivity to the addiction-related effects of JWH-018, as evidenced by their increased responses in intravenous SA ( Figures 3A–C ) and CPP ( Figure 3E ) tests compared to WT mice. While several studies have reported the addiction-like effects of synthetic cannabinoids, including JWH-018 ( Hur et al, 2021 ), in healthy rodent subjects ( Cha et al, 2014 ; de Luca et al, 2015 ), some cannabinoids still do not exhibit significant abuse potential in animal behavioral paradigms ( Tampus et al, 2015 ; Bilel et al, 2019 ). This suggests the involvement of complex neurological mechanisms (that mediate the addictive effects of cannabinoids) other than the typical mesolimbic dopaminergic pathway.…”

Considerations for Cannabinoids in Perioperative Care by Anesthesiologists

“…However, this is a misleading term, as psychoactive properties are not the only desirable trait, even if they are the most popular trait of these compounds. Several inert cannabinoids have not been characterized in depth despite interesting pharmacology [4,6,9,11,54,59]. To add to the complexity of the presented landscape, cannabinoids can be synthesized de novo [10,43].…”

“…Several inert cannabinoids have not been characterized in depth despite interesting pharmacology [4,6,9,11,54,59]. To add to the complexity of the presented landscape, cannabinoids can be synthesized de novo [10,43].…”