This laboratory study will evaluate whether a cannabinoid enhances the analgesic efficacy of an opioid in a clinical sample of chronic pain patients, laying the foundation for a larger clinical trial evaluating the utility of cannabinoids as potentially opioid-sparing adjuvants to chronic opioid therapy for pain. Heightened CNS processing, or central sensitization (CS), occurs across numerous chronic pain conditions and is an important treatment target in its own right. While cannabinoids show initial promise as treatments or adjuncts for some chronic pain conditions and pre-clinical data suggest effects on CS, little is known about the degree to which combining cannabinoids with opioids alleviates CS-mediated chronic pain. We propose a within-subject, single exposure, double-blind, placebo-controlled, human laboratory investigation of the extent to which a cannabinoid enhances opioid analgesia in a model chronic pain population (e.g., patients with knee osteoarthritis). Human laboratory studies are an ideal method for this initial evaluation because they provide the opportunity to tightly control study drug dosing and afford high sensitivity of measurements, and enable tight control of confounding variables that may otherwise exist in clinical treatment populations and could differentially impact outcomes. This approach will minimize the number of participants needed to determine whether a positive signal exists while permitting rigorous and elegant evaluation of the study aims. Primary study outcomes will include measures of clinical pain and central sensitization, physical function, drug effects (e.g., abuse liability, adverse events, cognitive performance), and pharmacokinetic analyses. The Aims will examine the magnitude and duration of cannabinoid/opioid combination in reducing clinical pain and central sensitization; the effects on physical functioning, adverse events and indices of abuse liability; and the pharmacokinetic and pharmacodynamics profiles for the individual and combined drugs. This study will provide the most systematic and rigorous evaluation of the potential for cannabinoids to enhance analgesic effects of opioids in human subjects to date, and will do so in a relevant and generalizable clinical pain population who has CS, which makes these results more directly relevant compared to studies conducted in healthy populations. These findings will be critical to informing the efficacy and safety profile for the advancement of opioid/cannabinoid combination regimens to clinical trials with chronic pain patients.