Evaluation of Cannabinoid Receptor 1 agonistic effects of synthetic cannabinoids in in vitro and in vivo
Synthetic cannabinoids (SCs) are one of most abused new psychoactive substances. While Cannabinoid receptor 1 (CB1) agonistic effects of natural cannabinoids are well understood, data related to novel SCs remains limited. In this study, we aimed to evaluate the CB1 agonistic effects of a total of 16 drugs, including a newly synthesized SCs in in vitro and in vivo. We also investigated to determine whether the results exhibited a direct correlation. For in vitro assay, Ca2+ assay was performed using CB1-Gα15 stable expressed cell line. The potency and efficacy of SCs was calculate as EC50 and Emax in comparison with those of JWH-018. 5F-MDMB-P7AICA and CUMYL-like showed higher or similar effects. MDA -like and LY-2183240 were considered to have a relatively weak CB1 agonistic effects. Consistent with the in vitro findings, catalepsy was strongly induced by 5F-MDMB-P7AICA and CUMYL-like drugs in in vivo study. To ascertain the existence of a correlation among these results, we executed Spearman rank correlation analysis. Reflecting on the rank of intensity of catalepsy induction, a very strong correlation was observed in EC50 (rank), accompanied by a strong correlation in Emax (rank) values. These results suggest that our in vitro model for assessing CB1 agonistic effects is appropriate for determining the potency and efficacy of SCs and serves as a reliable metric for evaluating newly synthesized SCs.
2024 Spring Convention