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.

Public Health Relevance

There is a significant public health need to reduce singular reliance upon opioids for effective long-term pain management as chronic opioid therapy results in myriad complications. This laboratory study will evaluate whether a cannabinoid increases the pain-reducing effects of an opioid dose in people with knee osteoarthritis. We will examine a variety of clinically relevant outcomes, including clinical pain, central sensitization, physical function, abuse liability and pharmacokinetics, which 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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hampson, Aidan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Dunn, Kelly E; Barrett, Frederick S; Bigelow, George E (2018) Naloxone formulation for overdose reversal preference among patients receiving opioids for pain management. Addict Behav 86:56-60