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
Katrina R Hamilton 1 2 3 4, Chung Jung Mun 1 5, Eliot Sadik 6, Cecilia L Bergeria 7, Andrew S Huhn 7, Traci J Speed 1, Ryan Vandrey 7, Kelly E Dunn 8, Claudia M Campbell 1
- 1Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences; Baltimore, MD, USA.
- 2Ohio University, Department of Psychology; Athens, Ohio, USA.
- 3Heritage College of Osteopathic Medicine, Department of Social Medicine; Athens, Ohio, USA.
- 4Heritage College of Osteopathic Medicine, Institute to Advance Population Health (ADVANCE); Athens, Ohio, USA.
- 5Arizona State University, Edson College of Nursing and Health Innovation; Phoenix, AZ, USA.
- 6Johns Hopkins University School of Medicine, Department of Physical Medicine and Rehabilitation; Baltimore, MD, USA.
- 7Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences; Baltimore, MD, USA.
- 8Kahlert Institute for Addiction Medicine, University of Maryland Baltimore School of Medicine; Baltimore, MD, USA.
Affiliationer
Background: This within-subject, double-blind, randomized, placebo-controlled study aimed to determine the acute analgesic and drug effects, and risk for extramedical use, of synthetic delta-9-tetrahydrocannabinol and hydromorphone, alone and in combination, in individuals with knee osteoarthritis (KOA).
Methods: Participants (N=21; 57% women; Mean age=63.4±6.4) with KOA received oral combinations of placebo, hydromorphone (2 mg), and dronabinol (10 mg): (1, initial session) hydromorphone+placebo, (remaining sessions randomized) (2) placebo+placebo, (3) dronabinol+placebo, and (4) hydromorphone+dronabinol. Clinical and experimentally induced pain (quantitative sensory testing; QST), physical and cognitive function, subjective drug ratings, and adverse events (AEs) were evaluated at baseline and 60-, 120-, 180-, 240-minutes post-dosing.
Results: 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 non-capsaicin (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-minute walking distance ηp 2 =0.028, Timed Up and Go ηp 2 =-0.027, total stair climb time ηp 2 =-0.005); all ps>.05. Secondary Outcomes : Hydromorphone impaired working memory accuracy compared to all conditions and produced greater Good Effects than placebo, ps≤.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, ps<.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 AE occurrence or severity (ps>.05).
Conclusions: Opioid and cannabinoid medications failed to produce robust analgesia in experimentally induced pain among patients with KOA. In contrast to preclinical studies, there was no evidence of synergistic analgesic effects by combining hydromorphone and dronabinol.
