Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches

Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the CB1 receptor (JWH-073, 081, and 210) and Delta9-tetrahydrocannabinol (Delta9-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. Ki values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed CB1 protein membranes to compare dependence potential with CB1 receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except Delta9-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the CB1 receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

Dependence Potential of Quetiapine: Behavioral Pharmacology in Rodents

Quetiapine is an atypical or second-generation antipsychotic agent and has been a subject of a series of case report and suggested to have the potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive. In this study, we examined quetiapine's dependence potential and abuse liability through animal behavioral tests using rodents to study the mechanism of quetiapine. Molecular biology techniques were also used to find out the action mechanisms of the drug. In the animal behavioral tests, quetiapine did not show any positive effect on the experimental animals in the climbing, jumping, and conditioned place preference tests. However, in the head twitch and self-administration tests, the experimental animals showed significant positive responses. In addition, the action mechanism of quetiapine was found being related to dopamine and serotonin release. These results demonstrate that quetiapine affects the neurological systems related to abuse liability and has the potential to lead psychological dependence, as well.