The substituent design and photophysical property manipulation are of paramount importance in fluorescent probe design, particularly crucial for chemically inactive molecules that lack reactive functional groups, such as synthetic cannabinoids. Here, a ratiometric fluorescent probe, 2-(5-phenyl-8-(4-(trifluoromethyl)phenyl)pyrimido[4,5-d]pyridazin-2-yl)phenol (DPTF), was selected and synthesized using trifluoromethyl as an electron acceptor for the sensitive and specific detection of one representative synthetic cannabinoid, JWH-018 (1-naphthyl(1-pentyl-1H-indol-3-yl)methanone). The DPTF probe, driven by intermolecular through-space charge transfer (TSCT), exhibits a theoretically calculated limit of detection (LOD) of 2.16 nmol/mL to liquid JWH-018, with low naked-eye detection limits of 101 nmol/mL for liquid JWH-018 and 147 nmol/mL on the porcelain spot plate, and also demonstrates good anti-interference capabilities with 18 substances. The practicability of the probe was further verified through testing E-liquid, urea, artificial saliva, local sewage, and cigarettes, successfully detecting trace amounts of impure JWH-018 in both simulated and real scenarios. Moreover, this work contributes to the probe design methods to understand the photophysical mechanisms that dominate molecular recognition, and we expect that the detection of synthetic cannabinoids is essential for comprehending their epidemiological spread and preventing incidents related to drug-impaired driving or violence.