CANNABINOID RECEPTOR MODULATORS: THERAPEUTIC POTENTIAL AND CHALLENGES

Abstract

Background

The endocannabinoid system (ECS) is an important regulatory network involved in maintaining physiological homeostasis in the nervous, immune, and metabolic systems. Cannabinoid receptors CB1 and CB2 represent promising therapeutic targets for various disorders.

Objective

This review aims to evaluate the therapeutic potential of cannabinoid receptor modulators and discuss the challenges associated with their clinical development.

Methods

A narrative literature review was conducted using published articles from peer-reviewed journals indexed in PubMed, Science Direct, Nature Reviews, British Journal of Pharmacology, and related databases. Studies focusing on cannabinoid receptors, allosteric modulators, biased ligands, therapeutic applications, and clinical limitations were analyzed.

Results

Evidence indicates that cannabinoid receptor modulators, particularly allosteric modulators and biased ligands, offer improved selectivity and safety compared with conventional agonists and antagonists. CB2-selective modulators demonstrated anti-inflammatory and analgesic effects with minimal psychoactivity, whereas CB1 allosteric modulators showed potential in neurological disorders, epilepsy, and neuroprotection. However, challenges including receptor selectivity, CNS toxicity, psychoactive effects, and regulatory barriers remain significant obstacles.

Conclusion

Cannabinoid receptor modulation represents a promising therapeutic strategy for numerous diseases. Advances in allosteric modulation, biased signaling, and peripheral receptor targeting may facilitate the development of safer and more effective cannabinoid-based therapeutics.