Cannabidiol-Δ9-tetrahydrocannabinol interactions on acute pain and locomotor activity

Drug Alcohol Depend. 2017 Jun 1:175:187-197. doi: 10.1016/j.drugalcdep.2017.01.046. Epub 2017 Apr 15.


Background: Previous studies suggest that cannabidiol (CBD) may potentiate or antagonize Δ9-tetrahydrocannabinol's (THC) effects. The current study examined sex differences in CBD modulation of THC-induced antinociception, hypolocomotion, and metabolism.

Methods: In Experiment 1, CBD (0, 10 or 30mg/kg) was administered 15min before THC (0, 1.8, 3.2, 5.6 or 10mg/kg), and rats were tested for antinociception and locomotion 15-360min post-THC injection. In Experiments 2 and 3, CBD (30mg/kg) was administered 13h or 15min before THC (1.8mg/kg); rats were tested for antinociception and locomotion 30-480min post-THC injection (Experiment 2), or serum samples were taken 30-360min post-THC injection to examine CBD modulation of THC metabolism (Experiment 3).

Results: In Experiment 1, CBD alone produced no antinociceptive effects, while enhancing THC-induced paw pressure but not tail withdrawal antinociception 4-6h post-THC injection. CBD alone increased locomotor activity at 6h post-injection, but enhanced THC-induced hypolocomotion 4-6h post-THC injection, at lower THC doses. There were no sex differences in CBD-THC interactions. In Experiments 2 and 3, CBD did not significantly enhance THC's effects when CBD was administered 13h or 15min before THC; however, CBD inhibited THC metabolism, and this effect was greater in females than males.

Conclusions: These results suggest that CBD may enhance THC's antinociceptive and hypolocomotive effects, primarily prolonging THC's duration of action; however, these effects were small and inconsistent across experiments. CBD inhibition of THC metabolism as well other mechanisms likely contribute to CBD-THC interactions on behavior.

Keywords: Cannabinoids; Gender; Pain; Sedation; Sex differences.

MeSH terms

  • Acute Pain / drug therapy*
  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Cannabidiol / pharmacology*
  • Dronabinol / pharmacology*
  • Drug Interactions
  • Female
  • Locomotion / drug effects*
  • Male
  • Rats
  • Sex Factors


  • Analgesics, Non-Narcotic
  • Cannabidiol
  • Dronabinol