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 Δ-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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634900PMC
http://dx.doi.org/10.1101/2023.10.26.564282DOI Listing

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