Development of a Cell Membrane Conformational Cannabinoid CB₁ Receptor Biosensor for the Detection of Synthetic...

This study aimed to develop a chemical structure-independent, sensitive screening platform for detecting novel synthetic cannabinoids using isolated cell membranes. Resonance energy transfer techniques were employed to detect conformational changes in the CB₁ receptor upon agonist binding. Eight cannabinoid CB₁ conformational biosensors were generated and characterized featuring different tag compositions and placements. The biosensors were initially tested in live cell assays, before conditions were optimized for activity in isolated cell membranes. The optimal sensor developed could successfully distinguish between different agonist efficacy and potency profiles. This biosensor allows for the detection of synthetic cannabinoids without relying on their chemical structure, potentially providing a valuable tool for compliance agencies to rapidly respond to the proliferation of new psychoactive substances. The ability to differentiate efficacy and potency profiles may also contribute to harm reduction strategies upon detection of these compounds.