Abstract
Cannabinoids are effective analgesics but induce adverse cannabimimetic effects and the development of tolerance. Allosteric ligands of the cannabinoid CB1 receptor (CB1) may harness the pain-relieving effects of cannabinoids with reduced adverse effects. CB1 allosteric ligands bind at a site topographically distinct from the orthosteric binding site. CB1 allosteric ligands have been shown to be effective pain-relieving drugs that do not appear to result in the production of adverse effects or the development of tolerance. While this therapeutic profile indicates that CB1 allosteric ligands could be an effective treatment for chronic pain, their molecular mechanism of action remains unclear.