Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01127-1.