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

Abstract

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.

Recent advances in the treatment and prevention of peripheral neuropathy after multiple myeloma treatment

“…It has been shown that cannabinoids can inhibit neuropathic pain caused by traumatic injury, toxic injury, and metabolic changes, although the mechanism of action of cannabinoid receptors in this process is not fully understood. Indeed, while the relevance of activation of DRG neurons by CB1 receptor (CB1 cannabinoid receptors, CB1R) to explaining the cannabinoid antinociceptive effects has been demonstrated by site‐specific drug administration and tissue‐selective knockdown, the main sites of CB2 receptor (CB2 cannabinoid receptors, CB2R) remain unclear 43 . Mulpuri et al 49 found that local or systemic application of 4‐{2‐[‐(1E)‐1[(4‐propylnaphthalen‐1‐yl)methylidene]‐1H‐inden‐3‐yl]ethyl} morpholine (PrNMI) dose‐dependently suppressed CIPN mechanical and cold allodynia without any CNS side effects.…”

“…Administration of bortezomib induces increased expression of the atypical cannabinoid receptor TRPV1 and an increase in the number of CB1R‐ and CB2R‐positive DRG neurons in the DRG and spinal cord dorsal horn. So cannabinoids are likely to be effective drugs for the effective treatment of BIPN 43 …”

“…Indeed, while the relevance of activation of DRG neurons by CB1 receptor (CB1 cannabinoid receptors, CB1R) to explaining the cannabinoid antinociceptive effects has been demonstrated by site‐specific drug administration and tissue‐selective knockdown, the main sites of CB2 receptor (CB2 cannabinoid receptors, CB2R) remain unclear. 43 Mulpuri et al 49 found that local or systemic application of 4‐{2‐[‐(1E)‐1[(4‐propylnaphthalen‐1‐yl)methylidene]‐1H‐inden‐3‐yl]ethyl} morpholine (PrNMI) dose‐dependently suppressed CIPN mechanical and cold allodynia without any CNS side effects. Administration of bortezomib induces increased expression of the atypical cannabinoid receptor TRPV1 and an increase in the number of CB1R‐ and CB2R‐positive DRG neurons in the DRG and spinal cord dorsal horn.…”

Paclitaxel-Associated Mechanical Sensitivity and Neuroinflammation Are Sex-, Time-, and Site-Specific and Prevented through Cannabigerol Administration in C57Bl/6 Mice

“…There is growing patient and research interest in cannabinoid constituents for the treatment of CIPN (see [22] for review). For example, we and others have demonstrated that both ∆ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), alone and in combination, can prevent the development of mechanical sensitivity associated with paclitaxel administration in male [23,24] or female [25,26] C57Bl/6 mice.…”

Single and Combined Effects of Cannabigerol (CBG) and Cannabidiol (CBD) in Mouse Models of Oxaliplatin-Associated Mechanical Sensitivity, Opioid Antinociception, and Naloxone-Precipitated Opioid Withdrawal

“…The scientific evidence, practice, and legislation surrounding the medical use of Cannabis for the treatment of chronic pain continues to rise, and there is growing patient and research interest in cannabinoid constituents for the treatment of CIPN (see [10] for review). We and others have demonstrated that both ∆ 9 -tetrahydrocannabinol (∆ 9 -THC) and cannabidiol (CBD) can prevent the development of mechanical sensitivity associated with chemotherapeutic administration in male [11,12] or female [13,14] C57BL/6 mice.…”