Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT 1A receptors without diminishing nervous system function or chemotherapy efficacy

Sara Jane Ward, Sean D. McAllister, Rumi Kawamura, Ryuchi Murase, Harshini Neelakantan, Ellen A. Walker

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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. Experimental Approach 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. Key Results 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.

Original languageEnglish (US)
Pages (from-to)636-645
Number of pages10
JournalBritish Journal of Pharmacology
Volume171
Issue number3
DOIs
StatePublished - Feb 2014
Externally publishedYes

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Cannabidiol
Receptor, Serotonin, 5-HT1A
Neuralgia
Paclitaxel
Nervous System
Drug Therapy
Cell Survival
rimonabant
Breast Neoplasms
Learning
Serotonin 5-HT1 Receptor Antagonists
Operant Conditioning
Withholding Treatment
Aptitude
Cannabinoids

Keywords

  • 5-HT
  • breast cancer
  • cannabidiol
  • cannabinoid
  • chemotherapy-induced neuropathic pain
  • CIPN
  • mechanical sensitivity
  • paclitaxel

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT 1A receptors without diminishing nervous system function or chemotherapy efficacy. / Ward, Sara Jane; McAllister, Sean D.; Kawamura, Rumi; Murase, Ryuchi; Neelakantan, Harshini; Walker, Ellen A.

In: British Journal of Pharmacology, Vol. 171, No. 3, 02.2014, p. 636-645.

Research output: Contribution to journalArticle

Ward, Sara Jane ; McAllister, Sean D. ; Kawamura, Rumi ; Murase, Ryuchi ; Neelakantan, Harshini ; Walker, Ellen A. / Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT 1A receptors without diminishing nervous system function or chemotherapy efficacy. In: British Journal of Pharmacology. 2014 ; Vol. 171, No. 3. pp. 636-645.
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