Analogues and Derivatives of Cannabidiol: Pharmacological Insights and Recent Efforts in the Search for Novel Drug Candidates for Inflammation and Pain - a Brief Review Over the Past 3 Decades

Cannabidiol is a metabolite present in Cannabis with several pharmacological properties, including neuroprotection, anti-convulsive, antimicrobial, antinociceptive, and anti-inflammatory. Although these activities are promising for drug development and clinical uses, the neuroprotective action is the most investigated, while the anti-inflammatory and antinociceptive mechanisms are not fully known. Therefore, this brief review aims to report the knowledge advances over the last 3 decades regarding the anti-inflammatory and anti-nociceptive/analgesic properties of cannabidiol and its derivatives or analogues designed as novel drug candidates. Recent studies of the mechanisms of action underlying the anti-inflammatory effects of cannabidiol have revealed its interaction with different inflammatory mediators, including cannabinoid receptor 1 and cyclooxygenase 2, among others. On the other hand, there is a lack of information related to the analgesic activity of cannabidiol, with some reports pointing out the involvement only of transient receptor potential vanilloid receptors. In addition, several cannabidiol derivatives and structural analogues with anti-inflammatory and antinociceptive activities have been described, but their mechanisms of action have not yet been fully elucidated. Therefore, it is clear that greater efforts are still needed to unravel the mechanisms involved in such activities of great interest in drug discovery.