The Subjective Psychoactive Effects of Oral Dronabinol Studied in a Randomized, Controlled Crossover Clinical Trial for Pain

Background: Many cannabinoid medications are approved in North America or in phase III trials, such as dronabinol, nabilone, or nabiximols. Little is known about their subjective psychoactive effects when used for pain management. We hypothesized that when used for pain, dronabinol has psychoactive effects in a dose-response relationship, whose peak effects are comparable with smoking Cannabis. Methods: This was a randomized controlled trial of single dose placebo, 10 or 20 mg dronabinol in 30 chronic noncancer pain patients taking opioids and not using Cannabis. Participants completed the Addiction Research Center Inventory (ARCI) hourly for 8 hours during 3 monitored sessions. Comparison sample was the ARCI ratings in participants with no pain (N=20), monitored every 30 minutes after smoking a 1.99% THC (low) and a 3.51% (high strength) Cannabis cigarette. Results: The 10 and 20 mg dronabinol doses had significantly elevated scores over time on 4/5 subscales versus placebo (P<0.05). Average daily morphine use, total pain relief (TOTPAR), age, sex, and baseline pain level were not significant covariates. ARCI peak effects at 2 hours were similar to peak effects of smoked Cannabis at 30 minutes (P=0.80, 10 mg=low strength, 20 mg=high strength). Conclusions: In pain patients, oral dronabinol has similar psychoactive effects to smoking Cannabis. This risk must be considered in any decision to prescribe cannabinoid medications for pain.