Efficacy of Dronabinol for Acute Pain Management in Adults with Traumatic Injury: Study Protocol of A Randomized Controlled Trial

Delta-9-tetrahydrocannabinol (Δ⁹-THC) and other cannabinoids present in cannabis (marijuana) have been shown to affect the normal inhibitory pathways that influence nociception in humans. The potential benefits of cannabinoids as an analgesic are likely greatest in hyperalgesic and inflammatory states, suggesting a role as a therapeutic agent for treating acute pain following injury. Dronabinol is a licensed form of Δ⁹-THC. The primary objective of this single center randomized controlled trial is to evaluate the efficacy of adjunctive dronabinol versus control (systemic analgesics only, no dronabinol) for reducing opioid consumption in adults with traumatic injury. Study inclusion is based on high baseline utilization of opioids ≥50 morphine equivalents (mg) within 24 h of admission for adults aged 18-65 years with traumatic injury. There is a 48-hour screening period followed by a 48-hour treatment period after randomization. A total of 122 patients will be randomized 1:1 across 2 study arms: adjunctive dronabinol versus control (standard of care using systemic analgesics, no adjunctive dronabinol). Patients randomized to the dronabinol arm should receive their first dose within 12 h of randomization, with a dose range of 5 mg up to 30 mg daily in divided doses, in addition to systemic analgesics as needed for pain. The primary efficacy endpoint is a change in opioid consumption (morphine equivalents), assessed post-randomization (48 h after randomization) minus pre-randomization (24 h prior to randomization). This is the first randomized trial to investigate whether adjunctive dronabinol is effective in reducing opioid consumption in acute pain management of traumatic injury. Trial Registration: ClinicalTrials.gov Identifier: NCT03928015.