The CB2 cannabinoid receptor as a therapeutic target in the central nervous system

Targeting CB2 cannabinoid receptor (CB2r) represents a promising approach for the treatment of central nervous system disorders. These receptors were identified in peripheral tissues, but also in neurons in the central nervous system. New findings have highlighted the interest to target these central receptors to obtain therapeutic effects devoid of the classical cannabinoid side-effects.

In this review, we searched PubMed (January 1991-May 2021), ClinicalTrials.gov and Cochrane Library databases for articles, reviews and clinical trials. We first introduce the relevance of CB2r as a key component of the endocannabinoid system. We discuss CB2r interest as a possible novel target in the treatment of pain. This receptor has raised interest as a potential target for neurodegenerative disorders treatment, as we then discussed. Finally, we underline studies revealing a novel potential CB2r interest in mental disorders treatment.

In spite of the interest of targeting CB2r for pain, clinical trials evaluating CB2r agonist analgesic efficacy have currently failed. The preferential involvement of CB2r in preventing the development of chronic pain could influence the failure of clinical trials designed for the treatment of already established pain syndromes. Specific trials should be designed to target the prevention of chronic pain development.