JWH-018 AND JWH-307: INTEGRATED PHARMACOLOGICAL AND PHARMACOKINETIC PROFILES

JWH-018 and JWH-307 are synthetic cannabinoids (SCBs) that induce psychological effects such as relaxation and euphoria. Due to their abuse potential, these compounds are regulated in many countries; However, pharmacological and pharmacokinetic characterization of these SCBs remains limited. In this study, we investigated the pharmacological and pharmacokinetic properties of JWH-018 and JWH-307. Cannabinoid receptor 1 (CB1R) binding assays were performed to evaluate the binding affinity of representative SCBs. JWH-018 exhibited high affinity for the receptor, whereas JWH-307 showed moderate affinity. To examine neurochemical alterations in the mesolimbic dopaminergic system, mice were repeatedly administered 0.05 mg/kg JWH-018 or 1 mg/kg JWH-307 every other day. Both compounds reduced the GABA to glutamate ratio in the ventral tegmental area (VTA) and increased dopamine levels in the nucleus accumbens (NAc). Western blot analysis revealed increased expression of CB1R, PKA, Akt, ERK and c-fos, while AC1 expression was decreased in both SCB treated groups. Pharmacokinetic profiles were assessed after 1 mg/kg intravenous and 10 mg/kg oral administration in mice. JWH-018 showed low plasma clearance and a small volume of distribution, whereas JWH-307 exhibited high plasma clearance and a moderate volume of distribution. JWH-018 displayed slow absorption and low bioavailability, while JWH-307 showed rapid absorption with similarly low bioavailability. These findings demonstrate the pharmacological and pharmacokinetic characteristics of JWH-018 and JWH-307, highlighting the requirement for strict regulation due to their high abuse potential. [Supported by the NRF(RS-2025-16067597) and the MFDS(23212MFDS218) of Korea.]