Structure-activity relationship of prevalent synthetic cannabinoid metabolites on hCB₁ in vitro and in silico dynamics.

ABSTRACT: Synthetic cannabinoids (SC) target the human cannabinoid receptor 1 (hCB₁) and are extensively metabolized, but the metabolite activity on the hCB₁ receptor after a SC intake is largely unknown. In this study we compared the in vitro hCB₁ receptor activity of 26 metabolites of the synthetic cannabinoid receptor agonists (SCRA) JWH-018, AM-2201, THJ-018 and THJ-2201 as a model system for SC metabolite activity to elucidate their structure-activity relationships. The efficacy and potency of metabolites were assessed using an AequoScreen hCB₁ receptor assay in triplicates and 7-8 concentration points (20 µg/mL-9.5 ng/mL) were used to construct dose-response curves and to determine EC₅₀ and E_max. In silico docking and molecular

SUBMITTER: Astrand A 

PROVIDER: S-EPMC12932713 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature