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

ObjectiveTo investigate the effect of cannabidiol (CBD) on sevoflurane minimum alveolar concentration (MAC_SEV) reduction produced by morphine in rats.Study designRandomized, blinded trial.AnimalsA total of 75 male Wistar Han rats weighing 276 ± 23 g (mean and standard deviation), aged 3 months.MethodsCannabidiol (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 < 0.05ResultsThe 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 relevanceMAC_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.