Oxycodone Self-Administration in Female Rats is Enhanced by Δ⁹-tetrahydrocannabinol, but not by Cannabidiol, in a Progressive Ratio Procedure

Abstract

Epidemiological evidence suggests that the legalization of cannabis may reduce opioid-related harms. Preclinical evidence of neuropharmacological interactions of endogenous cannabinoid and opioid systems prompts further investigation of cannabinoids as potential therapeutics for the non-medical use of opioids. In these studies female rats, previously trained to self-administer oxycodone (0.15 mg/kg/infusion) intravenously in 6 h sessions, were allowed to self-administer oxycodone after exposure to cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) by vapor inhalation and THC by injection (5.0-20 mg/kg, i.p.). Self-administration was characterized under Progressive Ratio (PR) and Fixed Ratio (FR) 1 schedules of reinforcement in 3 h sessions. THC decreased IVSA of oxycodone in a FR procedure but increased reward seeking in a PR procedure. CBD decreased the IVSA of oxycodone in the FR but not the PR procedure. The results are consistent with an anti-reward effect of CBD but suggest THC acts to increase the reinforcing efficacy of oxycodone in this procedure.

Impact of Δ9-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

“…When nonpreference producing doses of Δ 9 -THC (3 mg/kg) and oxycodone (1 mg/kg) were administered, it resulted in the development of CPP in both sexes. These findings parallel recent literature reporting that vaporized or injected Δ 9 -THC reduces oxycodone (Nguyen et al, 2019;Nguyen et al, 2021;Nguyen et al, 2023) and heroin (Gutierrez et al, 2022) self-administration in rats. The authors in (Nguyen et al, 2021;Nguyen et al, 2023) suggest that Δ 9 -THC may be increasing the rewarding efficacy of a "unit dose" of oxycodone when self-administered.…”

“…These findings parallel recent literature reporting that vaporized or injected Δ 9 -THC reduces oxycodone (Nguyen et al, 2019;Nguyen et al, 2021;Nguyen et al, 2023) and heroin (Gutierrez et al, 2022) self-administration in rats. The authors in (Nguyen et al, 2021;Nguyen et al, 2023) suggest that Δ 9 -THC may be increasing the rewarding efficacy of a "unit dose" of oxycodone when self-administered. Our findings in the CPP paradigm are consistent with this hypothesis.…”