Adolescent rats repeatedly inhaling THC vapor developed tolerance to THC-induced hypothermia, with females showing tolerance earlier than males despite similar THC levels in the blood. In adulthood, both sexes retained tolerance, but THC potency was enhanced in females. Male rats exposed to adolescent THC ate more food than controls without gaining more weight. Adolescent THC exposure did not change oxycodone self-administration in either sex but increased fentanyl self-administration in females. The authors conclude that repeated THC vapor inhalation during adolescence has lasting consequences observable in adulthood.
Combined Δ9-tetrahydrocannabinol (THC) and oxycodone produced additive pain-relieving effects while reducing opioid self-administration in rats. Male rats trained to self-administer oxycodone intravenously obtained fewer infusions after inhaling vaporized THC or receiving injected THC (0-10 mg/kg, i.p.) compared to vehicle. Follow-up tests showed dose-dependent reductions across different oxycodone doses, with an intact loading dose arguing against general behavioral suppression. In separate groups of male and female Wistar rats, tail withdrawal latency increased more after inhaled THC (50 mg/mL) plus oxycodone (100 mg/mL) than either alone; similar additive antinociception occurred with injected THC (5.0 mg/kg, i.p.) and oxycodone (2.0 mg/kg, s.c.). These additive effects suggest THC could enhance opioid therapeutic efficacy and reduce abuse.