Chapter 23 Cannabidiolic acid (CBDA), features and profiles: Anti-hyperalgesic effects

Persistent neuropathic pain involves nerve damage, changing communication networks between the extremities and the central nervous system, and may be associated with hyperalgesia. Prescribed opioids often cause intolerable side effects including hyperalgesia in patients experiencing chronic pain. Novel therapeutics that ameliorate painful sensitivities and improve quality of life need to be characterized and clinically applied. Nonpsychotropic phytocannabinoids such as the potent precursor of cannabidiol, cannabidiolic acid (CBDA), provide anti-hyperalgesia in inflammatory models. Other molecules present in plant extracts may influence efficacy, with CBDA also undergoing natural decarboxylation. A synthetic derivative, CBDA methyl ester (CBDA-ME), represents a promising antihyperalgesic agent in a preclinical model of peripherally induced neuropathic pain. Its mechanisms of action require further characterization in males and females, as each sex responded differently. The optimal timing of its administration also needs to be determined to evaluate whether treatment prior to inducing a nerve injury prevents hyperalgesia. Since CBDA-ME does not have toxic side effects, it could be rapidly adapted for clinical use.