Evaluating the Acute Effects of the Cannabinoid Dronabinol and the Opioid Hydromorphone Alone and in Combination: A Double-blind, Randomized, Placebo-controlled Trial in Knee Osteoarthritis.

Abstract

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. 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. 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). 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.