Light-Controlled Modulation of the Endocannabinoid System: Photoswitchable Ligands for Cannabinoid and TRPV1 Receptors

Photopharmacology is an emerging field in medicinal chemistry that seeks to control the pharmacological effects of target compounds using light. This approach addresses challenges such as limited receptor selectivity by enabling precise spatiotemporal control of therapeutic effects. The light-responsiveness is a central molecular feature used in photopharmacology to modulate the activity of various biological systems, including the endocannabinoid system (ECS). Although the ECS plays a well-established role in the treatment of neurodegeneration, inflammation, and pain, targeting its receptors is challenging due to side effects resulting from receptor activation or inactivation and the incomplete selectivity of available ligands. In this review, we present a comprehensive analysis of the most important ECS photoagonists and photoantagonists, highlighting how this photopharmacological approach overcomes traditional limitations of therapeutic targeting and reduces off-target effects.