Objective

To investigate the effect of cannabidiol (CBD) on sevoflurane minimum alveolar concentration (MAC_SEV) reduction produced by morphine in rats.

Study design

Randomized, blinded trial.

Animals

A total of 75 male Wistar Han rats weighing 276 ± 23 g (mean and standard deviation), aged 3 months.

Methods

Cannabidiol (CBD) was prepared in an ethanol-solutol-saline vehicle. Animals were randomly divided into 15 groups and given an intraperitoneal bolus of 1, 3, 5, 6.5, 7.5 or 10 mg kg⁻¹ of CBD alone (CBD1, CBD3, CBD5, CBD6.5, CBD7.5 and CBD10 respectively) or combined with 5 mg kg⁻¹ of morphine (MOR+CBD1, MOR+CBD3, MOR+CBD5, MOR+CBD6.5, MOR+CBD7.5 and MOR+CBD10). While three controls groups: MOR+saline, MOR+vehicle and vehicle were given an intraperitoneal bolus of morphine with saline, morphine with vehicle or vehicle alone respectively. The MAC_SEV was determined from alveolar gas samples at the time of tail clamp application. The MAC_SEV reduction was analyzed using a one-way ANOVA followed by Tukey’s test. Additionally, Kruskal-Wallis test for non-normally-distributed data was performed. Data are presented as mean ± standard deviation. P < 0.05

Results

The mean MAC_SEV was not reduced by the action of CBD administered alone, but the addition of morphine to the different doses of CBD significantly reduced the MAC_SEV. That reduction was greatest in the MOR+CBD1, MOR+CBD7.5 and MOR+CBD10 groups (29 ± 5%, 32 ± 5% and 30 ± 6% respectively), less in MOR+CBD3 and MOR+CBD6.5 groups (24 ± 3% and 26 ± 4% respectively) and least in MOR+CBD5 group (17 ± 2%). However, only the MOR+CBD5 group was statistically significantly different from MOR+CBD1, MOR+CBD7.5 and MOR+CBD10 groups.

Conclusions and clinical relevance

MAC_SEV in rat was unaltered by the action of CBD alone, the reduction in MAC_SEV produced by morphine was not enhanced by the addition of CBD at the doses studied.

中文翻译：

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大麻二酚对吗啡致大鼠七氟醚最小肺泡浓度降低的影响

客观的

研究大麻二酚 (CBD) 对吗啡引起的大鼠七氟醚最小肺泡浓度 (MAC _SEV ) 降低的影响。

学习规划

随机、盲法试验。

动物

总共 75 只雄性 Wistar Han 大鼠，体重 276 ± 23 g（平均值和标准偏差），3 个月大。

方法

大麻二酚 (CBD) 在乙醇-溶质-盐水载体中制备。将动物随机分为 15 组，并给予1、3、5、6.5、7.5或 10 mg kg ^-1单独的 CBD（分别为 CBD1、CBD3、CBD5、CBD6.5、CBD7.5 和 CBD10）腹膜内推注或结合 5 mg kg ^-1的吗啡（MOR+CBD1、MOR+CBD3、MOR+CBD5、MOR+CBD6.5、MOR+CBD7.5 和 MOR+CBD10）。而三个对照组：MOR+盐水、MOR+载体和载体分别给予含盐水的吗啡、吗啡和载体或单独的载体的腹膜内推注。MAC _SEV是在尾夹应用时从肺泡气体样本中确定的。MAC _SEV使用单向方差分析和 Tukey 检验分析减少。此外，还对非正态分布数据进行了 Kruskal-Wallis 检验。数据表示为平均值±标准偏差。P < 0.05

结果

平均 MAC _SEV并未因单独施用 CBD 的作用而降低，但将吗啡添加到不同剂量的 CBD 中显着降低了 MAC _SEV。这种降低在 MOR+CBD1、MOR+CBD7.5 和 MOR+CBD10 组中最大（分别为 29±5%、32±5% 和 30±6%），在 MOR+CBD3 和 MOR+CBD6.5 组中较少（分别为 24 ± 3% 和 26 ± 4%）并且在 MOR+CBD5 组中最少（17 ± 2%）。然而，只有 MOR+CBD5 组与 MOR+CBD1、MOR+CBD7.5 和 MOR+CBD10 组有统计学显着差异。

结论和临床相关性

大鼠中的MAC _SEV未因 CBD 的单独作用而改变，添加所研究剂量的 CBD 并未增强吗啡产生的MAC _SEV的降低。