The effect of cannabidiol on sevoflurane minimum alveolar concentration reduction produced by morphine in rats.

OBJECTIVE

To investigate the effect of cannabidiol (CBD) on sevoflurane minimum alveolar concentration (MAC) 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 of CBD alone (CBD1, CBD3, CBD5, CBD6.5, CBD7.5 and CBD10 respectively) or combined with 5 mg kg 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 was determined from alveolar gas samples at the time of tail clamp application. The MAC 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 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. 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 in rat was unaltered by the action of CBD alone, the reduction in MAC produced by morphine was not enhanced by the addition of CBD at the doses studied.