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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 DELTA9-tetrahydrocannabinol (THC) enhances the behavioral effects of oxycodone. Male rats were trained to intravenously self-administer (IVSA) oxycodone (0.15mg/kg/infusion) during 1h, 4h or 8h sessions. Following acquisition rats were exposed to THC by vapor inhalation (1h and 8h groups) or injection (0-10mg/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 (50mg/mL), oxycodone (100mg/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 (5.0mg/kg, i.p.) and oxycodone (2.0mg/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. Copyright © 2019 Elsevier Ltd. All rights reserved.

41 citations (Crossref) [2023-10-31] Place: England Nguyen, Jacques D. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Grant, Yanabel. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Creehan, Kevin M. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Hwang, Candy S. Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, La Jolla, CA, USA; Department of Chemistry, Southern Connecticut State University, New Haven, CT, USA. Vandewater, Sophia A. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA. Janda, Kim D. Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, La Jolla, CA, USA. Cole, Maury. La Jolla Alcohol Research, Inc, La Jolla, CA, USA. Taffe, Michael A. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. Electronic address: mtaffe@ucsd.edu.