Repeated cannabinoids injection increases cocaine-induced behavioral response in adolescent rats in a sex dependent manner.

The use of cannabis oil has grown significantly across all age groups. It is usually a mixture of Cannabidiol (CBD) and Tetrahydrocannabinol (THC). THC, which has psychostimulant effects, may enhance the response to first cocaine exposure, potentially increasing the risk of developing addiction. Adolescents are especially vulnerable to the effects of psychoactive substances. However, there is limited evidence on how low repeated doses of CBD and/or THC affect adolescent response to cocaine. We administered 10 injections of CBD (9 mg/kg, i.p.) and/or THC (3 mg/kg, i.p.) or vehicle to male and female rats starting on postnatal days 30-33. Two or 10 days after finishing the treatment, we assessed their basal behaviors (i.e., anxiety-like behaviors, ALB) and their locomotor response to cocaine (5 mg/kg, i.p.). We found significant sex differences in ALB: CBD increased it in males, whereas THC decreased it in females. Females also showed greater susceptibility to cocaine. Interestingly, CBD enhanced cocaine responses in females 2 days post-treatment, THC reduced it, and CBD+THC appeared to balance these effects. On the other hand, a cocaine injection after 10 days of THC treatment significantly increased locomotor activity compared to controls. Our results suggest that low-dose cannabinoid treatments during adolescence influence anxiety-like behaviors and cocaine responses differently based on sex. Ongoing experiments will assess CBD and CBD+THC after 10 days.