Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy
Version of Record online: 13 JAN 2014
© 2013 The British Pharmacological Society
British Journal of Pharmacology
Special Issue: Themed Section: Biological Sex and Cardiovascular Pharmacology. Guest Editors: Barbara J McDermott and Gillian A Gray
Volume 171, Issue 3, pages 636–645, February 2014
How to Cite
Ward, S. J., McAllister, S. D., Kawamura, R., Murase, R., Neelakantan, H. and Walker, E. A. (2014), Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy. British Journal of Pharmacology, 171: 636–645. doi: 10.1111/bph.12439
- Issue online: 13 JAN 2014
- Version of Record online: 13 JAN 2014
- Accepted manuscript online: 4 OCT 2013 04:05AM EST
- Manuscript Accepted: 26 AUG 2013
- Manuscript Revised: 12 AUG 2013
- Manuscript Received: 10 MAR 2013
- chemotherapy-induced neuropathic pain;
- breast cancer;
- mechanical sensitivity
Background and Purpose
Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy.
The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay.
PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg−1) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT1A antagonist WAY 100635, but not the CB1 antagonist SR141716 or the CB2 antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability.
Conclusions and Implications
Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN.