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

**Authors:** Alessia Agata Corallo, Carlotta Noli, Antonella Brizzi, Marco Paolino, Claudia Mugnaini, Federico Corelli

PMC · DOI: 10.3390/ijms27020573 · 2026-01-06

## TL;DR

This paper reviews how light-controlled drugs can precisely target the endocannabinoid system, improving treatment of conditions like pain and inflammation.

## Contribution

The paper introduces photoswitchable ligands that enable precise control of endocannabinoid system receptors using light.

## Key findings

- Photoswitchable ligands allow spatiotemporal control of endocannabinoid system activity.
- These compounds reduce off-target effects and improve receptor selectivity.
- Photopharmacology offers a novel approach to modulate cannabinoid and TRPV1 receptors.

## Abstract

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.

## Linked entities

- **Proteins:** TRPV1 (transient receptor potential cation channel subfamily V member 1)

## Full-text entities

- **Diseases:** neurodegeneration (MESH:D019636), pain (MESH:D010146), inflammation (MESH:D007249)
- **Chemicals:** Cannabinoid (MESH:D002186), Endocannabinoid (MESH:D063388)

## Figures

35 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12841161/full.md

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Source: https://tomesphere.com/paper/PMC12841161