Behavioral and biochemical effects of Cannabis Sativa and their modulation by antidepressant drugs

We aimed to study the effect of Cannabis sativa on brain oxidative stress and determine whether behavioral responses caused by cannabis could be reversed by standard antidepressant drugs. Cannabis sativa (5, 10 or 15 mg/kg) (expressed as Δ9-tetrahydrocannabinol) was given alone or with fluoxetine, sertraline or imipramine, once daily subcutaneously (s.c.) for 24 days. In the forced-swimming test, the immobility time, was significantly increased in mice treated with cannabis (5-15 mg/kg, s.c.) starting from the 9th day post-injection. Fluoxetine (20 mg/kg, s.c.) coadministered with cannabis (5 mg/kg, s.c.) resulted in significant decrease in the immobility time by the day 21 of the study compared with the cannabis only group. Mice co-administered sertraline or imipramine with cannabis were not statistically different from the vehicle control group as regards their immobility time. Cannabis resulted in a significant decrease in the rearing activity which was ameliorated by either fluoxetine or sertraline. Cannabis sativa increased brain reduced glutathione, but decreased the level of nitric oxide. Fluoxetine, sertraline or imipramine given with cannabis decreased malondialdehyde and increased reduced glutathione. In conclusion: The administration of cannabis decreases brain oxidative stress but exerts depressive-like effect and decreases rearing activity which can be reversed by antidepressant drugs.