Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 46; no. 8; pp. 1451 - 1459
• Main Authors: Dunn, Kelly E., Bergeria, Cecilia L., Huhn, Andrew S., Speed, Traci J., Mun, Chung Jung, Vandrey, Ryan, Campbell, Claudia M.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.07.2021; Nature Publishing Group
• Subjects: 692/308/1426; 692/308/409; Adult; Adverse events; Analgesia; Analgesics, Opioid; Behavioral Sciences; Biological Psychology; Blindness; Cannabinoids; Capsaicin; Chronic pain; Clinical trials; Cognitive ability; Double-Blind Method; Dronabinol; Drug abuse; Humans; Hydromorphone; Laboratories; Medicine; Medicine & Public Health; Narcotics; Neurosciences; Opioids; Pain; Pain - drug therapy; Pain perception; Pharmacotherapy; Placebos; Psychiatry; Tetrahydrocannabinol
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/s41386-021-01007-4

This Phase II study evaluated analgesia, abuse liability, and cognitive performance of hydromorphone and oral delta-9-tetrahydrocannabinol (THC; dronabinol) using a within-subject, double-blind, randomized, placebo-controlled, human laboratory trial. Healthy adults ( N  = 29) with no history of drug use disorder received combinations of placebo, hydromorphone (4 mg; oral), and dronabinol (2.5 mg, 5.0 mg, 10 mg; oral). Primary outcomes were quantitative sensory testing (QST) measures of acute (thermal, pressure pain; thermal, punctate probe temporal summation; cold pressor; conditioned pain modulation) and chronic pain (capsaicin 10% topical cream with thermal rekindling), measures of drug abuse liability, cognitive functioning, and adverse events. Subgroup analyses were conducted within opioid-responders (endorsed >20 on a Drug Effect visual analog scale during the hydromorphone-only condition) and nonresponders. A consistent dose-effect relationship of dronabinol on hydromorphone across all measures was not observed. Analgesia only improved in the hydromorphone + dronabinol 2.5 mg condition. Hydromorphone + dronabinol 2.5 mg showed the lowest and hydromorphone+dronabinol 5 mg showed the highest risk for abuse. Hydromorphone+dronabinol 10 mg produced a high rate of dysphoric effects, and hydromorphone+dronabinol 5 mg and hydromorphone + dronabinol 10 mg produced AEs. Subgroup analyses showed subjective effects and abuse risk was increased among opioid responders and largely absent among nonresponders. Overall, only hydromorphone+dronabinol 2.5 mg modestly enhanced hydromorphone-based analgesia and hydromorphone + dronabinol 5 mg and 10 mg increased risk for abuse and AEs. These data can help inform opioid-sparing efforts in clinical pain populations. Demonstration that potential opioid effects varied as a function of participant opioid sensitivity (e.g., responder status) is a novel finding that warrants additional research.