Assessment of the Abuse Liability of Synthetic Cannabinoid Agonists JWH-030, JWH-175, and JWH-176

The emergence and use of synthetic cannabinoids have greatly increased in recent years. These substances are easily dispensed over the internet and on the streets. Some synthetic cannabinoids were shown to have abuse liability and were subsequently regulated by authorities. However, there are compounds that are still not regulated probably due to the lack of abuse liability studies. In the present study, we assessed the abuse liability of three synthetic cannabinoids, namely JWH-030, JWH-175, and JWH-176. The abuse liability of these drugs was evaluated in two of the most widely used animal models for assessing the abuse potential of drugs, the conditioned place preference (CPP) and self-administration (SA) test. In addition, the open-field test was utilized to assess the effects of repeated (7 days) treatment and abrupt cessation of these drugs on the psychomotor activity of animals. Results showed that JWH-175 (0.5 mg/kg), but not JWH-030 or JWH-176 at any dose, significantly decreased the locomotor activity of mice. This alteration in locomotor activity was only evident during acute exposure to the drug and was not observed during repeated treatment and abstinence. Similarly, only JWH-175 (0.1 mg/kg) produced significant CPP in rats. On the other hand, none of the drugs tested was self-administered by rats. Taken together, the present results indicate that JWH-175, but not JWH-030 and JWH-176, may have abuse potential. More importantly, our findings indicate the complex psychopharmacological effects of synthetic cannabinoids and the need to closely monitor the production, dispensation, and use of these substances.