Δ9-tetrahydrocannabinol (THC) Increases the Rewarding Value of Oxycodone During Self-Administration in Rats

Background: Cannabis may reduce the nonmedical use of prescription opioids. Causality of polydrug use is difficult to establish from epidemiological data, and thus controlled laboratory models can test whether cannabinoid co-use with opioids can modulate opioid intake. Methods: Male and female rats were trained to intravenously self-administer (IVSA) oxycodone (0.15 mg/kg/infusion) during 6 h sessions. Separate groups were injected with the vehicle or with THC (5 mg/kg, i.p.; N=10) 30 minutes before sessions for the first three weeks. Treatments were swapped in the fourth week. One male group was trained in the intracranial self-stimulation (ICSS) procedure and assessed for brain reward thresholds prior to each IVSA session. Results: THC treated animals self-administered less oxycodone during acquisition, with a larger differential expressed in the female group. Tolerance to the THC effect developed over the initial weeks, and increasing the dose of THC (10 mg/kg, i.p.) prolonged the suppressing effect on IVSA. While ICSS thresholds increased with sequential IVSA sessions, no differences between THC- and Vehicle-treated groups were observed. Oxycodone IVSA was increased following the first 60 h abstinence interval in THC-treated, but not vehicle-treated, rats. Acute injection of THC, when all animals had been THC abstinent for several weeks, increased breakpoints in a Progressive Ratio procedure. Conclusion: These data support the interpretation that THC enhances the reinforcing efficacy of a given dose of oxycodone and may therefore increase the addiction liability. ### Competing Interest Statement The authors have declared no competing interest.