Δ9-tetrahydrocannabinol attenuates oxycodone self-administration under extended access conditions.

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.

Study at a glance

Abstract

Growing nonmedical use of prescription opioids is a global problem, motivating research on ways to reduce use and combat addiction. Medical cannabis ("medical marijuana") legalization has been associated epidemiologically with reduced opioid harms and cannabinoids have been shown to modulate effects of opioids in animal models. This study was conducted to determine if Δ9-tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone. Male rats were trained to intravenously self-administer (IVSA) oxycodone (0.15 mg/kg/infusion) during 1 h, 4 h or 8 h sessions. Following acquisition rats were exposed to THC by vapor inhalation (1 h and 8 h groups) or injection (0-10 mg/kg, i.p.; all groups) prior to IVSA sessions. Fewer oxycodone infusions were obtained by rats following vaporized or injected THC compared with vehicle treatment prior to the session. Follow-up studies demonstrated parallel dose-dependent effects of THC, i.p., on self-administration of different per-infusion doses of oxycodone and a preserved loading dose early in the session. These patterns are inconsistent with behavioral suppression. Additional groups of male and female Wistar rats were assessed for nociception following inhalation of vaporized THC (50 mg/mL), oxycodone (100 mg/mL) or the combination. Tail withdrawal latency was increased more by the THC/oxycodone combination compared to either drug alone. Similar additive antinociceptive effects were produced by injection of THC (5.0 mg/kg, i.p.) and oxycodone (2.0 mg/kg, s.c.). Together these data demonstrate additive effects of THC and oxycodone and suggest the potential use of THC to enhance therapeutic efficacy, and to reduce the abuse, of opioids.