The effects of cannabidiol, Δ9-tetrahydrocannabinol, and combinations of cannabidiol and Δ9-tetrahydrocannabinol in the open field test and forced swim test

Background. Depression is the most common psychiatric comorbidity in people living with epilepsy, affecting approximately 25–35% of patients. Antidepressants are typically prescribed for depression, but they only provide relief in about two-thirds of patients. Recent research suggests that the cannabinoids might provide a new therapy for depression in both epileptic and non-epileptic patients. Methods. The effects of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), and combinations of CBD and THC were tested in a mouse model of depression (the forced swim test, FST) and locomotor activity (the open field test, OFT). Adult, male CD-1 mice were injected intraperitoneally with CBD (0 or 30 mg/kg), THC (0 or 2 mg/kg) or CBD + THC (0 + 0, 30 + 1, 30 + 2 mg/kg). They were then tested for 30 min in the OFT and for 6 min in the FST. Results. As compared to vehicle, CBD, and THC both significantly decreased the time spent immobile and increased the time spent swimming in the FST. THC, however, also significantly increased locomotor activity in the OFT, suggesting a non-specific effect. In combination, CBD and THC lost their effects in both tests and did not differ from vehicle. Conclusions. These results suggest that CBD might be potentially useful for people living with depression. In the present study, however, combinations of CBD and THC had an infra-additive effect rather than the supra-additive effect reported in a previous study. Since CBD and THC in combination produced effects that are less than the sum of the drugs alone (1 + 1 > 2), this may suggest the presence of antagonistic interactions between these two cannabinoids. This research was conducted with the support of EpLink - the Epilepsy Research Program of the Ontario Brain Institute.