Background: This within-subject, double-blind, randomized, placebo-controlled study aimed to determine the acute analgesic and drug effects and the risk for extramedical use, of synthetic delta-9-tetrahydrocannabinol and hydromorphone, alone and in combination, in individuals with knee osteoarthritis.
Methods: Participants (N = 21; 57% women; mean age = 63.4 ± 6.4 yr) with knee osteoarthritis received oral combinations of placebo, hydromorphone (2 mg), and dronabinol (10 mg). In the initial session, participants received hydromorphone + placebo, and the remaining sessions were randomized, with participants receiving placebo + placebo, dronabinol + placebo, or hydromorphone + dronabinol. Clinical and experimentally induced pain (quantitative sensory testing), physical and cognitive function, subjective drug ratings, and adverse events were evaluated at baseline and at 60, 120, 180, and 240 min after dosing.
Results: For primary outcomes, hydromorphone produced greater pressure pain threshold analgesia than dronabinol ( P = 0.029, ηp 2 = 0.074), greater capsaicin ( P = 0.045, ηp 2 = 0.062), and noncapsaicin ( P = 0.017, ηp 2 = 0.087) sensitized mechanical temporal summation analgesia than placebo. There were no significant drug-related differences for clinical pain severity (ηp 2 = 0.011), thermal threshold (ηp 2 = -0.025) or tolerance (ηp 2 = -0.008), temporal summation (ηp 2 = 0.009), cold pressor (ηp 2 = 0.056), conditioned pain modulation (ηp 2 = 0.038), capsaicin-induced thermal threshold (ηp 2 = -0.030), central sensitization (ηp 2 = 0.006), general pain sensitivity (ηp 2 = 0.021), or physical functioning (2-min walking distance [ηp 2 = 0.028], Timed Up and Go [ηp 2 = -0.027], and total stair climb time [ηp 2 = -0.005]; all P values > 0.05). For secondary outcomes, hydromorphone impaired working memory accuracy compared to all conditions and produced greater good effects than placebo (all P ≤ 0.005); hydromorphone + dronabinol impaired working memory reaction time and produced greater high ratings compared to placebo, greater drug effects than placebo and hydromorphone, and higher nausea than hydromorphone (all P < 0.05); and dronabinol had greater high ratings than hydromorphone ( P = 0.001). There were no significant drug-related differences for fine motor movement, bad effects, drug liking, or adverse event occurrence or severity (all P > 0.05).
Conclusions: Opioid and cannabinoid medications failed to produce robust analgesia in experimentally induced pain among patients with knee osteoarthritis. In contrast to preclinical studies, there was no evidence of synergistic analgesic effects by combining hydromorphone and dronabinol.
Rural hospitals operate on thin margins, sustained largely by federal funding through Medicaid and bolstered by the Affordable Care Act premium subsidies. As these supports erode due to recent federal legislative changes through the One Big, Beautiful Bill Act and a failure of the U.S. Congress to renew Affordable Care Act monies, millions will lose affordable insurance. For anesthesiologists, these changes will translate into closed healthcare systems, cancelled cases, less coverage for medication-assisted treatment used in opioid use disorder, and shrinking surgical capacity. These changes will be disproportionately felt in rural America, where residents already faced disparities in health care. Protecting coverage and rural hospital funding is not just a matter of equity; it is central to maintaining safe, timely anesthesia care for millions of Americans.
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