The antiemetic interaction of Delta(9)-tetrahydrocannabinol when combined with tropisetron or dexamethasone in the least shrew

5-HT3 receptor antagonists (e.g. tropisetron) combined with dexamethasone are effective for the acute phase of cisplatin (CIS)-induced emesis. This Study determined the possible additive or synergistic antiemetic efficacy of Delta(9)-THC when combined with tropisetron or dexamethasone (DEX). Delta(9)-THC (0-10 mg/kg i.p.) was injected in combination with tropisetron (0-5 mg/kg i.p.) or dexamethasone (0-20 mg/kg i.p.) prior to CIS (20 mg/kg i.p.) in the least shrew, and the induced emesis was recorded for 60 min. CIS-induced vomiting was dose-dependently and significantly attenuated by individual administration of Delta(9)-THC (59-97% reductions) and tropisetron (79-100% attenuation), but not dexamethasone (26-40%), although a trend (p < 0.1) towards reduced vomiting frequency following DEX was noted. Low doses of Delta(9)-THC (0.25 or 0.5 mg/kg) when combined with low doses of tropisetron (0.025, 0.1, or 0.25 mg/kg) were more efficacious in reducing emesis frequency than when given individually, but Delta(9)-THC had no antiemetic interactions with DEX. However, no tested combination provided a significantly greater effect on the number of animals vomiting than their individually-administered counterparts. The modest interaction of Delta(9)-THC with tropisetron suggests they activate overlapping antiemetic mechanisms, while the lack of interaction with dexamethasone needs further clarification. (c) 2008 Elsevier Inc. All rights reserved.