Δ 9 -tetrahydrocannabinol (THC) Increases the Rewarding Value of Oxycodone During Self-Administration in Rats
Jacques D. Nguyen, Yanabel Grant, Celine Yang, Michael A. Taffe
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled laboratory experiment in rats |
|---|---|
| Population | Male and female rats self-administering intravenous oxycodone |
| Interventions | THC Oxycodone |
| Dose | THC 5 mg/kg, i.p. (increased to 10 mg/kg, i.p.); oxycodone 0.15 mg/kg/infusion |
| Duration | First three weeks of treatment, with treatments swapped in the fourth week; 60 h abstinence interval; several weeks of THC abstinence before acute injection |
| Measures | Intravenous self-administration (IVSA), intracranial self-stimulation (ICSS) brain reward thresholds, Progressive Ratio breakpoints |
| Topics | Cannabis |
| Key findings | THC-treated rats self-administered less oxycodone during acquisition, an effect larger in females that showed tolerance over weeks and was prolonged by a higher THC dose. After 60 hours of abstinence, oxycodone intake rose in THC-treated but not vehicle-treated rats, and acute THC after weeks of abstinence increased breakpoints. The authors interpret this as THC enhancing the reinforcing efficacy of oxycodone and possibly increasing addiction liability. |
Abstract
Abstract:
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.