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

Overview

Journal Neurotherapeutics

Specialty Neurology

Date 2021 Oct 20

PMID 34668147

Citations 6

Authors

Guido Cavaletti

Paola Marmiroli

Cynthia L Renn

Susan G Dorsey

Maria Pina Serra

Marina Quartu

Cristina Meregalli

Affiliations

Soon will be listed here.

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.

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References

Meregalli C, Marjanovic I, Scali C, Monza L, Spinoni N, Galliani C . High-dose intravenous immunoglobulins reduce nerve macrophage infiltration and the severity of bortezomib-induced peripheral neurotoxicity in rats. J Neuroinflammation. 2018; 15(1):232. PMC: 6103882. DOI: 10.1186/s12974-018-1270-x. View

Galiegue S, MARY S, Marchand J, Dussossoy D, Carriere D, Carayon P . Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem. 1995; 232(1):54-61. DOI: 10.1111/j.1432-1033.1995.tb20780.x. View

Deng L, Cornett B, Mackie K, Hohmann A . CB1 Knockout Mice Unveil Sustained CB2-Mediated Antiallodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain. Mol Pharmacol. 2015; 88(1):64-74. PMC: 4468646. DOI: 10.1124/mol.115.098483. View

Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin C, Brenner G . Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat Neurosci. 2007; 10(7):870-9. PMC: 2234438. DOI: 10.1038/nn1916. View

Anand U, Otto W, Sanchez-Herrera D, Facer P, Yiangou Y, Korchev Y . Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain. 2008; 138(3):667-680. DOI: 10.1016/j.pain.2008.06.007. View

Meregalli C, Chiorazzi A, Carozzi V, Canta A, Sala B, Colombo M . Evaluation of tubulin polymerization and chronic inhibition of proteasome as citotoxicity mechanisms in bortezomib-induced peripheral neuropathy. Cell Cycle. 2013; 13(4):612-21. DOI: 10.4161/cc.27476. View

Gewandter J, Brell J, Cavaletti G, Dougherty P, Evans S, Howie L . Trial designs for chemotherapy-induced peripheral neuropathy prevention: ACTTION recommendations. Neurology. 2018; 91(9):403-413. PMC: 6133627. DOI: 10.1212/WNL.0000000000006083. View

Heyman E, Gamelin F, Goekint M, Piscitelli F, Roelands B, Leclair E . Intense exercise increases circulating endocannabinoid and BDNF levels in humans--possible implications for reward and depression. Psychoneuroendocrinology. 2011; 37(6):844-51. DOI: 10.1016/j.psyneuen.2011.09.017. View

Koltyn K, Brellenthin A, Cook D, Sehgal N, Hillard C . Mechanisms of exercise-induced hypoalgesia. J Pain. 2014; 15(12):1294-1304. PMC: 4302052. DOI: 10.1016/j.jpain.2014.09.006. View

10.

Quartu M, Carozzi V, Dorsey S, Serra M, Poddighe L, Picci C . Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve. Biomed Res Int. 2014; 2014:180428. PMC: 4022313. DOI: 10.1155/2014/180428. View

11.

Fernandez-Aranda F, Sauchelli S, Pastor A, Gonzalez M, de la Torre R, Granero R . Moderate-vigorous physical activity across body mass index in females: moderating effect of endocannabinoids and temperament. PLoS One. 2014; 9(8):e104534. PMC: 4125187. DOI: 10.1371/journal.pone.0104534. View

12.

Staff N, Grisold A, Grisold W, Windebank A . Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol. 2017; 81(6):772-781. PMC: 5656281. DOI: 10.1002/ana.24951. View

13.

Mulpuri Y, Marty V, Munier J, Mackie K, Schmidt B, Seltzman H . Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation. Neuropharmacology. 2018; 139:85-97. PMC: 6883926. DOI: 10.1016/j.neuropharm.2018.07.002. View

14.

Cabral G, Ferreira G, Jamerson M . Endocannabinoids and the Immune System in Health and Disease. Handb Exp Pharmacol. 2015; 231:185-211. DOI: 10.1007/978-3-319-20825-1_6. View

15.

Tofthagen C, Cheville A, Loprinzi C . The Physical Consequences of Chemotherapy-Induced Peripheral Neuropathy. Curr Oncol Rep. 2020; 22(5):50. DOI: 10.1007/s11912-020-00903-0. View

16.

Starobova H, Vetter I . Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy. Front Mol Neurosci. 2017; 10:174. PMC: 5450696. DOI: 10.3389/fnmol.2017.00174. View

17.

Lynch M, Cesar-Rittenberg P, Hohmann A . A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage. 2013; 47(1):166-73. DOI: 10.1016/j.jpainsymman.2013.02.018. View

18.

Berman J, Symonds C, Birch R . Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004; 112(3):299-306. DOI: 10.1016/j.pain.2004.09.013. View

19.

Kleckner I, Kamen C, Gewandter J, Mohile N, Heckler C, Culakova E . Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial. Support Care Cancer. 2017; 26(4):1019-1028. PMC: 5823751. DOI: 10.1007/s00520-017-4013-0. View

20.

McKallip R, Lombard C, Martin B, Nagarkatti M, Nagarkatti P . Delta(9)-tetrahydrocannabinol-induced apoptosis in the thymus and spleen as a mechanism of immunosuppression in vitro and in vivo. J Pharmacol Exp Ther. 2002; 302(2):451-65. DOI: 10.1124/jpet.102.033506. View