This is the first study to examine the effect of dronabinol for acute pain management following traumatic injury. These preliminary data suggest adjunctive dronabinol used as part of a multimodal analgesia regimen may result in a marked reduction in opioid consumption. The opioid-sparing effect appears to be more pronounced in patients who are marijuana users. Adjunctive dronabinol did not lead to corresponding reductions in pain scores, although both groups experienced similar reductions in pain and the dronabinol group achieved this reduction while also significantly reducing their opioid consumption. The promising results of this study have led us to initiate a randomized controlled trial to formally evaluate the efficacy of dronabinol for reducing opioid consumption following traumatic injury (clinicaltrials.gov identifier: NCT03928015).

There is little research for cannabinoid use in acute pain management. A 2017 systematic review assessed the analgesic efficacy of cannabinoid medications in acute pain management in seven studies, which included a total of 116 patients.15 In this review, article acute pain was defined as ‘pain of recent onset and probably limited duration’, which aligns with our definition of acute pain following traumatic injury. Of the seven cannabinoid studies, two studies included dronabinol.17 18 Buggy et al randomized patients 1:1 to Δ⁹-THC 5 mg versus placebo for pain related to elective abdominal hysterectomies in 40 patients.17 A single dose was given on the second postoperative day when patients requested analgesia, with no statistical difference in pain scores at rest and movement between the groups. In a study by Seeling et al, patients were either given dronabinol 5 mg or placebo for acute pain following radical prostatectomy with regional lymphadenectomy; no differences in the resting pain score were observed between groups.18

Aligning with the above studies, our matched cohort study also demonstrated no significant difference in pain scores among patients who received dronabinol compared with their matched controls. However, pain scores are subjective and thus may not be the most appropriate measure of efficacy when examining acute pain management. The addition of dronabinol resulted in reduced opioid consumption that coincided with reduced pain scores in both groups, suggesting a beneficial opioid-sparing effect of dronabinol in acutely painful conditions.

As the USA is currently fighting an opioid epidemic, where the Centers for Disease Control and Prevention estimate 130 Americans are dying daily from opioid overdose, the use of dronabinol to decrease opioid use is an attractive option.19 Colorado was a leading state in legalizing both medical and recreational marijuana. The Colorado Department of Public Health Environment estimates that 40.4% of adults use marijuana in some form (inhalation, ingestion).20 Because our study showed that the opioid-sparing effect of dronabinol may be greatest in patients who use marijuana, use of dronabinol adjunctively may benefit nearly half of the state’s population.

Severe pain is commonly experienced following traumatic injury and needs to be treated with medication. There are several reasons we believe adding adjunctive dronabinol may be favorable to increasing narcotic dosages in patients whose pain is not well managed: (1) the addictive tendency of marijuana and the negative effects of that addiction on patient morbidity and (especially) mortality are magnitudes less for marijuana than for narcotics; (2) in the acute care setting, the effects of dronabinol on vascular neurological response and respiratory depression are not as significant as with narcotics, especially when dronabinol is used adjunctively to reduce or maintain the opioid regimen rather than increasing narcotic dosages to detrimentally high levels; (3) our providers use dronabinol only during the initial phase to get the patient through the acute trauma episode. Patients are not routinely discharged with dronabinol, and other pain medications are conservatively prescribed at discharge. This practice limits over prescription of dronabinol and narcotics.

One of our study’s objectives was to determine whether the effect of dronabinol is more pronounced in marijuana users. The gestalt is that home marijuana users would have a more profound decrease in their opioid consumption with dronabinol; this has not yet been reported in the acute setting and is one of the main findings of our study. Nearly half of patients who received dronabinol were not current marijuana users, reflecting the decision to prescribe dronabinol to be multifactorial and not based solely on marijuana use. Still, there were differences in marijuana use between cases and controls, likely reflecting clinicians’ preference to prescribe dronabinol to marijuana users. A limitation of this study is that patients were not matched by self-reported marijuana use. Our randomized controlled trial uses a stratified block randomization design that randomizes patients 1:1 based on pre-injury marijuana use; this design should elucidate whether there is an opioid-sparing effect of dronabinol, and whether it is similar for marijuana users and marijuana-naïve patients.

Additional limitations to our study exist. First, we did not examine adverse events, although no cases needed to be discontinued from dronabinol. Other studies have suggested that any beneficial effects of cannabis-based medicines may be offset by potential harms.3 14 It is possible that the risk versus benefit ratio may be more favorable in acutely painful conditions because the treatment period and total dosing should be less than that seen in chronic painful conditions. The median treatment period in our study was 3 days, whereas a Cochrane review of cannabis-based medicines for chronic painful neuropathy included studies with a treatment duration of 14–182 days.14 Second, controls did not receive dronabinol, so the pretreatment period was estimated to be the first 48 hours from admission. This estimate was based on the median time from admission to first administration of dronabinol among cases of 55 hours. While there were no differences in the time from admission to the start of the ‘post’period for cases and controls, some cases may have been prescribed dronabinol later in the hospital stay, whereas the ‘post’period for all controls was 48–96 hours from admission. Third, we do not know why controls were not prescribed dronabinol or if they refused dronabinol. Fourth, our results may not be generalizable to hospitals in states where marijuana is illegal because they might expect a lower prevalence of marijuana use among the trauma population. Fifth, marijuana use was based on self-report because only 13 patients had a urine toxicology screening; of those, 12 patients tested positive for drugs, including 7 cases and 5 controls. Sixth, we do not know whether patients who received dronabinol were more satisfied with their hospital pain control compared with those who received opioids without adjunctive dronabinol; satisfaction could be considered a more relevant outcome to self-reported pain NRS scores. Finally, we did not study whether other cannabinoids can be used as analgesics in acutely painful conditions because our institution does not have other cannabis-based medications on formulary.