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A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew).
Psychopharmacology (Berl) 2004; 174(2):254-9P

Abstract

RATIONALE

The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, delta9-tetrahydrocannabinol (delta9-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.

OBJECTIVE

To evaluate the potential of: 1) a broad range of doses of delta9-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 delta9-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), delta9-THC (1.25-10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg delta9-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 delta9-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 delta9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews.

Authors+Show Affiliations

Department of Psychology, Wilfrid Laurier University, Waterloo, Ontario, N2L 3C5, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14740147

Citation

Kwiatkowska, Magdalena, 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, vol. 174, no. 2, 2004, pp. 254-9.
Kwiatkowska M, Parker LA, 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 (Berl). 2004;174(2):254-9.
Kwiatkowska, M., Parker, L. A., Burton, P., & Mechoulam, R. (2004). A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology, 174(2), pp. 254-9.
Kwiatkowska M, 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 (Berl). 2004;174(2):254-9. PubMed PMID: 14740147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). AU - Kwiatkowska,Magdalena, AU - Parker,Linda A, AU - Burton,Page, AU - Mechoulam,Raphael, PY - 2004/1/24/pubmed PY - 2004/10/20/medline PY - 2004/1/24/entrez SP - 254 EP - 9 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 174 IS - 2 N2 - RATIONALE: The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, delta9-tetrahydrocannabinol (delta9-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. OBJECTIVE: To evaluate the potential of: 1) a broad range of doses of delta9-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 delta9-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), delta9-THC (1.25-10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg delta9-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 delta9-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 delta9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/14740147/A_comparative_analysis_of_the_potential_of_cannabinoids_and_ondansetron_to_suppress_cisplatin_induced_emesis_in_the_Suncus_murinus__house_musk_shrew__ L2 - https://dx.doi.org/10.1007/s00213-003-1739-9 DB - PRIME DP - Unbound Medicine ER -