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Cannabinoids: Current and Future Options to Treat Chronic and Chemotherapy-Induced Neuropathic Pain

Abstract

Increases in cancer diagnosis have tremendous negative impacts on patients and their families, and major societal and economic costs. The beneficial effect of chemotherapeutic agents on tumor suppression comes with major unwanted side effects such as weight and hair loss, nausea and vomiting, and neuropathic pain. Chemotherapy-induced peripheral neuropathy (CIPN), which can include both painful and non-painful symptoms, can persist 6 months or longer after the patient’s last chemotherapeutic treatment. These peripheral sensory and motor deficits are poorly treated by our current analgesics with limited effectiveness. Therefore, the development of novel treatment strategies is an important preclinical research focus and an urgent need for patients. Approaches to prevent CIPN have yielded disappointing results since these compounds may interfere with the anti-tumor properties of chemotherapeutic agents. Nevertheless, the first (serotonin noradrenaline reuptake inhibitors [SNRIs], anticonvulsants, tricyclic antidepressants) and second (5% lidocaine patches, 8% capsaicin patches and weak opioids such as tramadol) lines of treatment for CIPN have shown some efficacy. The clinical challenge of CIPN management in cancer patients and the need to target novel therapies with long-term efficacy in alleviating CIPN are an ongoing focus of research. The endogenous cannabinoid system has shown great promise and efficacy in alleviating CIPN in preclinical and clinical studies. In this review, we will discuss the mechanisms through which the platinum, taxane, and vinca alkaloid classes of chemotherapeutics may produce CIPN and the potential therapeutic effect of drugs targeting the endocannabinoid system in preclinical and clinical studies, in addition to cannabinoid compounds diffuse mechanisms of action in alleviation of CIPN.

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Acknowledgements

This work is dedicated to my beloved mother, Manon Marcotte, who passed away from lymphoma on January 3, 2011 (JG), and all the people who have lost their battles against cancer and to all those who are still fighting this dreadful disease. Special acknowledgement is given to Terri Lloyd, who is currently fighting triple-negative breast cancer and is an Admissions Director for the Graduate School of Biomedical Sciences at Texas Tech University Health Sciences Center.

Funding

Funding

This work has been supported by the National Institute on Drug Abuse (DA044999-01A1) (DJM and JG), the Texas Tech University Health Sciences Center School of Medicine (Grant 121035) (JG), the CH Foundation (MN), and the Cancer Prevention and Research Institute of Texas (RP140008) (KP).

Conflict of interest

The authors, Henry L. Blanton, Jennifer Brelsfoard, Nathan DeTurk, Kevin Pruitt, Madhusudhanan Narasimhan, Daniel J. Morgan and Josée Guindon, declare that they have no competing interests.

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Blanton, H.L., Brelsfoard, J., DeTurk, N. et al. Cannabinoids: Current and Future Options to Treat Chronic and Chemotherapy-Induced Neuropathic Pain. Drugs 79, 969–995 (2019). https://doi.org/10.1007/s40265-019-01132-x

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