Planta Med 2016; 82(13): 1169-1172
DOI: 10.1055/s-0042-106303
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice

Hannah M. Harris
1   Department of Psychology, University of Mississippi, University, MS, USA
,
Kenneth J. Sufka
1   Department of Psychology, University of Mississippi, University, MS, USA
2   Department of Pharmacology, University of Mississippi, University, MS, USA
3   National Center for Natural Products Research, University of Mississippi, University, MS, USA
,
Waseem Gul
3   National Center for Natural Products Research, University of Mississippi, University, MS, USA
,
Mahmoud A. ElSohly
3   National Center for Natural Products Research, University of Mississippi, University, MS, USA
4   Department of Pharmaceutics, University of Mississippi, University, MS, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 05. Februar 2016
revised 30. März 2016

accepted 02. April 2016

Publikationsdatum:
23. Mai 2016 (online)

Abstract

Sativex, a cannabinoid extract with a 1 : 1 ratio of tetrahydocannabinol and cannabidiol, has been shown to alleviate neuropathic pain associated with chemotherapy. This research examined whether tetrahydocannabinol or cannabidiol alone could attenuate or prevent cisplatin-induced tactile allodynia. In experiment 1, mice (C57BL/6) received eight administrations of 2.3 mg/kg cisplatin or saline solution IP every other day to induce tactile allodynia. Mice were then administered vehicle, 100 mg/kg gabapentin, 2 mg/kg tetrahydocannabinol, or 2 mg/kg cannabidiol IP and tested 60 min later on an electronic Von Frey. In experiment 2, prevention studies, cannabidiol (0.0, 0.5, 1.0, and 2.0 mg/kg) or tetrahydocannabinol (0.0, 0.5, 1.0, and 2.0 mg/kg) was given IP 30 min prior to cisplatin administration (2.3 or 1.0 mg/kg) utilizing a six-dose alternate day protocol. In both studies, tactile responses to the hind paws were quantified in g of force using an electronic Von Frey prior to and after the cisplatin administration protocol. Cisplatin produced a reduction in g of force indicative of neuropathy that was attenuated by gabapentin, tetrahydocannabinol, and cannabidiol but not prevented by either cannabinoid. These data demonstrate that each of the major constituents of Sativex alone can achieve analgesic effects against cisplatin neuropathy.

Supporting Information

 
  • References

  • 1 Valeberg BT, Rustøen T, Bjordal K, Hanestad BR, Paul S, Miaskowski C. Self-reported prevalence, etiology, and characteristics of pain in oncology outpatients. Eur J Pain 2008; 12: 582-590
  • 2 Kumar SP. Cancer pain: A critical review of mechanism-based classification and physical therapy management in palliative care. Indian J Palliat Care 2011; 17: 116-126
  • 3 Grisold W, Cavaletti G, Windeback AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention. Neuro Oncol 2012; 14: iv45-iv54
  • 4 Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. J Peripher Nerv Syst 2008; 13: 27-46
  • 5 Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M. Incidence, prevalence and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 2014; 155: 2461-2470
  • 6 Kannarkart G, Lasher EE, Schiff D. Neurologic complications of chemotherapy agents. Curr Opin Neurol 2007; 20: 719-725
  • 7 Paice JA. Chronic treatment-related pain in cancer survivors. Pain 2010; 152: S84-S89
  • 8 Wolf S, Barton D, Kottschade L, Grothery A, Loprinzi C. Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur J Cancer 2008; 44: 1507-1515
  • 9 Chiou LC, Hu SS, Ho Y. Targeting the cannabinoid system for pain relief?. Acta Anaesthesiol Taiwan 2013; 51: 161-170
  • 10 Rahn EJ, Thakur GA, Wood JAT, Zvonok AM, Makrynannis A, Hohmann AG. Pharmacological characterization of AM1710, a putative cannabinoid CB2 agonist from the cannbilactone class: antinociception without central nervous system side-effects. Pharmacol Biochem Behav 2011; 98: 493-502
  • 11 Curto-Reyes V, Botok T, Hidalgo A, Menéndez L, Baamonde A. Antinociceptive effects induced through the stimulation of spinal cannabinoid type 2 receptors in chronically inflamed mice. Eur J Pharmacol 2011; 668: 184-189
  • 12 Vera G, Cabezos PA, Martín MI, Abalo R. Characterization of cannabinoid-induced relief of neuropathic pain in a rat model of cisplatin-induced neuropathy. Pharmacol Biochem Behav 2013; 105: 205-212
  • 13 Guindon J, Lai Y, Takacs SM, Bradshaw HB, Hohmann AG. Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment. Pharmacol Res 2013; 67: 94-109
  • 14 Khasabova IA, Khasabov S, Paz J, Harding-Rose C, Simone DA, Seybold VS. Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy. J Neurosci 2012; 32: 7091-7101
  • 15 Alexander A, Smith PF, Rosengren RJ. Cannabinoids in the treatment of cancer. Cancer Lett 2009; 285: 6-12
  • 16 Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med 2011; 51: 1054-1061
  • 17 Rahn EJ, Hohmann AG. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics 2009; 6: 713-737
  • 18 Nurmikko TJ, Seprell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterized by allodynia: a randomized, double-blind, placebo-controlled clinical trial. Pain 2007; 133: 210-220
  • 19 Pisanti S, Picardi P, DʼAlessandro A, Laezza C, Bifulco M. The endocannabinoid signaling system in cancer. Trends Pharmacol Sci 2013; 34: 273-282
  • 20 Hart S, Fischer OM, Ullrich A. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res 2004; 64: 1943-1950