Discussion
pain
CHRONIC PAIN
The present study rigorously and comprehensively evaluated the effects of co-administering dronabinol (10 mg) and hydromorphone (4 mg) on evoked and clinical pain, self-reported drug effects, HAP metrics, physical and cognitive functioning, and AEs in patients with chronic pain. Overall, our findings reveal limited clinical benefits, and suggest that co-administering dronabinol (10 mg) with hydromorphone (4 mg) to this clinical population demonstrated a slightly enhanced risk for use along with elevated risk for AEs in the combined condition. These findings were consistent across sexes (see online supplement Table We found that although hydromorphone + dronabinol was associated with significant analgesia on several QST outcomes, it was not different than hydromorphone by itself, indicating no added benefit of the combination at the doses tested. We also found that none of the drug conditions significantly changed ratings of clinical pain severity. Overall, these findings are consistent with previous laboratory studies with healthy adults demonstrating limited additive benefit of combined cannabinoids and opioids on analgesia [To our knowledge, the present study is the first to evaluate the individual and combined effects of dronabinol and hydromorphone on clinically-relevant standardized physical testing measures [Relative to hydromorphone, dronabinol significantly increased the percent of participants who rated feeling High ≥ 60, a cutoff discussed by HAP experts as a metric of future risk. This value is higher than what was observed in prior studies [Despite several strengths, the present study had a number of limitations. First, only a single dose of hydromorphone and dronabinol was used, precluding dose-dependent examinations. A more parametric, dose-dependent design was considered but rejected due to concerns about feasibility of completing numerous sessions given that participants were older adults with chronic pain. In lieu of that design, the study assessed the highest cannabinoid dose tested by our prior research to provide maximal opportunity to detect the presence of any effect (whereas it would be more challenging to infer whether lack of effect smaller doses represented true lack of effect or a dose-related issue). The more definitive test for this line of research would be a full dose-dependent evaluation. In addition, the average participant age was >60 years old, which has been associated with changes in drug metabolism that may have impacted results. Third, use of an oral synthetic THC formulation may limit the data generalizability. Many advocates for the synergistic properties of cannabis prefer different routes of administration (e.g., inhalation) arguing that the whole, natural cannabis flower produces different effects than THC alone and could interact with opioids or produce analgesia in ways we do not yet fully understand. Fourth, although necessary for safety purposes, the hydromorphone condition was unrandomized which may have introduced order effects. Fifth, a longer walking test (6-min vs. 2-min) may have increased clinical pain levels and revealed more nuances in physical performance, but was shortened due to participant burden. Lastly, we focused on the acute effects of dronabinol and hydromorphone co-administration, and thus we cannot inform the long-term use of these two drugs on clinical outcomes, side effects, and HAP.