A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew).
BACKGROUND
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.
Kwiatkowska
Magdalena
M
Department of Psychology, Wilfrid Laurier University, Waterloo, Ontario, N2L 3C5, Canada.
Parker
Linda A
LA
Burton
Page
P
Mechoulam
Raphael
R
D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000633:toxicity*; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D008094:Lithium / Q000633:toxicity; D008297:Male; D017294:Ondansetron / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D010880:Piperidines / Q000633:toxicity; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D011720:Pyrazoles / Q000633:toxicity; D000077285:Rimonabant; D012788:Shrews; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D002186:Cannabinoids; D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D017294:Ondansetron; D013759:Dronabinol; D008094:Lithium; D002945:Cisplatin; D000077285:Rimonabant