Fig. 2

Effect of CBD on morphine-induced supraspinal antinociception. Mice received 10 nmol CBD icv 10 min before 6 nmol morphine, and analgesia was evaluated with the thermal warm water (52 °C) “tail-flick” test at the indicated post-opioid intervals. Each point represents the mean ± SEM of data from eight to ten mice. a CBD exhibited no significant analgesic effect in this test. The analgesia produced by the combination of CBD and morphine was significantly higher than that produced by morphine alone. The σ1R agonist PPCC did not alter morphine analgesia, but icv-injection 20 min before CBD prevented the enhancement of this effect of morphine. b The σ1R agonist BD1063 did not produce analgesia in this test but increased morphine antinociception. This potentiation was absent when PPCC was injected icv 20 min before BD1063. c Morphine promotes a higher analgesic effect in σ1R^−/− mice than in wild type control mice. In σ1R^−/− mice, BD1063 and CBD did not modify morphine analgesia. *Significantly different from the control group receiving only 6 nmol morphine, φ significantly different from the effect of morphine in wild-type mice. ANOVA, Dunnett’s multiple comparison vs control group, p < 0.05