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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).

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.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Psychology, Wilfrid Laurier University, Waterloo, Ontario, N2L 3C5, Canada.

    , ,

    Source

    Psychopharmacology 174:2 2004 Jul pg 254-9

    MeSH

    Animals
    Antiemetics
    Antineoplastic Agents
    Cannabinoids
    Cisplatin
    Dose-Response Relationship, Drug
    Dronabinol
    Drug Therapy, Combination
    Female
    Lithium
    Male
    Ondansetron
    Piperidines
    Psychotropic Drugs
    Pyrazoles
    Rimonabant
    Shrews
    Vomiting

    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 -