A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew)

Abstract

Rationale

The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC), have been shown to interfere with emesis; however, their relative and/or combined effectiveness in suppressing vomiting produced by the chemotherapeutic agent, cisplatin, is unknown.

Objectives

To evaluate the potential of: 1) a broad range of doses of Δ9-THC and OND to prevent cisplatin-induced vomiting and retching in the Suncus murinus (house musk shrew), 2) combined treatment with ineffective individual doses of Δ9-THC and OND to prevent cisplatin-induced vomiting and retching, 3) the CB1 receptor antagonist, SR141716, to reverse the antiemetic effects of OND, and 4) cannabidiol (CBD), the principal non-psychoactive component of marijuana, to reverse cisplatin-induced vomiting in the shrew.

Methods

Shrews were injected with various doses of OND (0.02–6.0 mg/kg), Δ9-THC (1.25–10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg Δ9-THC) prior to being injected with cisplatin (20 mg/kg) which induces vomiting. Shrews were also injected with CBD (5 mg/kg and 40 mg/kg) prior to an injection of cisplatin.

Results

OND and Δ9-THC both dose-dependently suppressed cisplatin-induced vomiting and retching. Furthermore, a combined pretreatment of doses of the two drugs that were ineffective alone completely suppressed vomiting and retching. CBD produced a biphasic effect, suppressing vomiting at 5 mg/kg and potentiating it at 40 mg/kg.

Conclusions

A low dose of the non-intoxicating cannabinoid CBD may be an effective anti-emetic treatment and combined doses of OND and Δ9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews.

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Acknowledgements

The research was supported by the research grant from the Canadian Institute of Health Research (CIHR) to LP and from the Israel Science Foundation and the National Institute on Drug Abuse to R.M. We thank Marion Corrick for breeding and excellent care of the shrews.

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Correspondence to Linda A. Parker.

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Kwiatkowska, M., Parker, L.A., Burton, P. et al. A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology 174, 254–259 (2004). https://doi.org/10.1007/s00213-003-1739-9

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Keywords

  • Vomiting
  • Chemotherapy
  • Serotonin
  • Retching
  • Nausea
  • Anandamide
  • Δ
  • -THC
  • Tetrahydrocannabinol
  • Cannabidiol
  • Ondansetron
  • Cancer