Department of Psychology, University of Guelph, Guelph, ON, Canada.
Br J Pharmacol. 2013 Jun;169(3):685-92. doi: 10.1111/bph.12162.
To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5-0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND).
We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined.
CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping.
CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients.
确定有效降低氯化锂（LiCl）诱导的条件性张口反应（恶心诱导行为）的大麻二酚酸（CBDA）最小有效剂量，并确定这些相对较低的全身剂量的 CBDA（5-0.1μg·kg⁻¹）是否能增强经典 5-羟色胺 3（5-HT₃）受体拮抗剂昂丹司琼（OND）的抗恶心作用。
我们研究了低剂量 CBDA 抑制急性恶心的功效，通过建立对 LiCl 配对味觉的条件性张口反应来评估。然后确定了 CBDA 的阈下和亚阈剂量增强 OND 降低恶心诱导的条件性张口的潜力。
CBDA（低至 0.5μg·kg⁻¹）抑制了味觉诱导的恶心性条件性张口。单独使用低剂量的 OND（1.0μg·kg⁻¹）即可减少恶心诱导的条件性张口，但当与亚阈剂量的 CBDA（0.1μg·kg⁻¹）联合使用时，LiCl 诱导的条件性张口的抑制作用增强。
CBDA 强烈抑制了大鼠的条件性张口，即使在低剂量下也能增强低剂量 OND 的抗恶心作用。这些发现表明，联合使用低剂量的 CBDA 和 OND 将更有效地治疗化疗患者的急性恶心。
