The primary findings from this pilot study suggest that marijuana use significantly affects acute pain management and results in increased consumption of opioid analgesics and greater self-reported pain following traumatic injury, especially in patients who did not report using other drugs. We also identified a low prevalence of other drug use but a relatively high prevalence of chronic marijuana use among trauma patients, especially in trauma centers in Colorado where marijuana has been legalized for both medical and recreational use.

To our knowledge, this is the first study to examine the effect of marijuana use and abuse on acute pain management following traumatic injury. We observed that marijuana’s effect on pain was modified by concomitant drug use. In drug users the addition of marijuana did not appear to effect opioid consumption unless it was used chronically. In non-drug users (representing 91% of our population), opioid administration over the course of the hospital stay was greatest for trauma patients who had used marijuana, both for chronic and episodic use compared to non-marijuana users, even after adjustment for injury severity, age, and specific type of MVC. This translates to a 25–37% increase in opioid consumption for marijuana users than non-marijuana users. Additionally, pain scores were significantly higher in marijuana users compared to non-users, even after adjustment for relevant confounders. The difference in pain scores in marijauna users vs. non-users (5.3 vs. 4.2) is striking when considering that pain scores ≤4 on a 0–10 scale are mild/moderate and scores of ≥5 are considered severe [26].

Prior studies report changes in acute pain management in opioid-tolerant patients, including an increase in opioid consumption [27,28,29]. Patanwala et al. were the first to prospectively compare the effect of opioid tolerance on the post-surgical analgesic response to opioids, demonstrating a significant increase in opioid consumption and greater pain NRS scores immediately after total knee arthroplasty in opioid tolerant patients relative to the naïve group [28]. Other studies examining opioid tolerance and post-operative pain management reported greater use of analgesics [29], and greater post-surgical requirement for epidural anesthesia [27] in patients who had prior opioid treatment. Neighbor and colleagues examined illegal substance abuse in the emergency department, which included cocaine, heroin, and amphetamine, reporting that substance abusers had significantly higher pain NRS scores compared to non-substance abusers at triage (8.96 vs. 7.81, p = 0.003) [30]. We also identified an association between marijuana use and abuse with acute pain management, and much like the opioid tolerant populations, identified chronic use of marijuana resulted in the greatest need for increased analgesia following injury.

Trauma patients commonly have substance abuse issues or other positive toxicology findings. There was a low prevalence of other drug use but a relatively high prevalence of chronic marijuana use, especially in trauma centers in Colorado. In our study 25% were acutely intoxicated, 21% used marijuana, and 9% used other drugs. Marijuana use was reported approximately 4 times more frequently in Colorado hospitals compared to the hospital in Texas. While the study is not designed to point to any causality related to the permissive marijuana laws, we were impressed by the prevalence of marijuana usage amongst our trauma populations. There appears to be a profound increase in marijuana use amongst trauma patients in the states with permissive marijuana laws. It is possible that the increased marijuana use leads to more motor vehicle collisions, but it is not possible to draw this conclusion based upon our data. This study should serve as a call to action for more research into the topic of legalization of marijuana.

We believe the increasing prevalence of marijuana use and other substance abuse issues will have clinical implications for acute pain management. Specifically, these data suggest that patients with marijuana use and abuse issues merit special consideration during acute pain management. These data may help set reasonable expectations for patients regarding the severity and duration of pain they experience, and could help clinicians recognize patients that are more likely to experience suboptimal pain management.

Despite its generally illicit status globally and its schedule I status in the US, there is a growing body of research examining endogenous cannabinoids (endocannabinoids) and exogenous cannabinoids as a target of pharmacotherapy [15]. Several endocannabinoids function to suppress pain sensitivity through their binding to the G-coupled CB1 and CB2 receptors [31]. The activation of these cannabinoid receptors inhibits calcium channels, resulting in activation of potassium channels and decreases in neurotransmitter release from several tissues [32, 33], including inhibition of norepinephrine release from sympathetic nerve terminals and diminished sympathetically mediated pain [15]. This activation of the cannabinoid receptors may be a potential mechanism of action for the antinociceptive effects of cannabinoids [34]. However, the antinociceptive effects of cannabinoids may respond to inflammatory, neurogenic, and chronic pain better than acutely evoked pain [35]. Other studies have demonstrated that the binding of endocannabinioids to CB1 receptors unexpectedly resulted in pain sensitization in in-vivo experiments, and may increase the risk of turning acute pain into chronic pain [36]. Thus, it is plausible that cannabis may be beneficial in treating chronic pain but may be detrimental in the acute pain setting.

There are study limitations. Primarily, this is a pilot study. Some subgroup sizes are low and possibly too small to draw valid conclusions. However, this is a pilot trial and is used as hypothesis generating in order to plan future studies. In the planned prospective study, approximately 360 patients are needed to adequately power the study. Second, the study has many of the disadvantages of a retrospective chart review. For instance, there is the possibility of exposure misclassification: patients were considered non-users if they had no urine drug toxicology screen or a negative toxicology screen and did not self-report using marijuana. Also, marijuana users without details on frequency of use were considered episodic users. Third, our findings might not be generalizable because we excluded minors and we chose to focus on patients who sustained MVC injuries because this population was thought to contain a high concentration of marijuana users. Marijuana consumption also increases the risk of non-traffic injuries, in particular falls in older adults [37], which is a population of interest for future study. Fourth, we excluded patients with a LOS > 14 days (10% of the population), because there is the possibility that the amount of opioids received for pain management over several weeks might lead to acute tolerance and increased opioid consumption unrelated to pre-injury drug and marijuana use [38]. Fifth, 14% of analgesics were non-opioids; we did not report differences in non-opioid analgesics, in part because of there is no standard approach to converting to equianalgesic doses. However, multimodal analgesia can achieve opioid-sparing effects, thereby affecting the data reported for opioid consumption. Lastly, patients who are conscious but non-verbal use a picture face scale, which also utilizes a pain NRS but there are fewer categories: 0 (no pain), 2 (just a little bit) 4 (hurts a little more), 6 (hurts even more), 8 (hurts a whole lot), and 10 (hurts as much as you can imagine). Only the anchor points of 0 and 10 are directly comparable to the pain NRS (0–10). Pain scores may be less accurate in patients with more severe injuries. This limitation should not bias our findings because there were no differences in injury severity (ISS or GCS) between marijuana users and non-users.