EXECUTIVE SUMMARY

Investigators are beginning to unearth important findings from a rich data set regarding cannabis-related ED visits at a large, academic medical center in Colorado. As states move to legalize recreational and/or medicinal cannabis use, the information is important to helping frontline providers understand how to recognize and treat such patients.

  • Investigators note the most common symptoms that brought cannabis users to the ED over a five-year period were intoxication, a cyclical vomiting condition, and acute psychiatric distress, such as psychosis, anxiety, panic attacks, or even suicidality and depression.
  • In a small number of patients, cardiovascular symptoms were observed. These included cardiac ischemia, an arrhythmia, or even a heart attack.
  • While users of edible products made up just a small percentage of cannabis users who presented to the ED, researchers found that their symptoms tended to be more intense or acute than for users of inhaled cannabis.

Colorado pioneered the legalization of cannabis for recreational use in 2014, and the idea has caught on elsewhere. Today, 33 states plus the District of Columbia have enacted laws legalizing the use of marijuana in some form. This means there is more opportunity for people to experience adverse drug events from cannabis use, and to end up in the ED as result.

Although such patients are not overwhelming EDs in Colorado or elsewhere, it is becoming increasingly important for frontline providers to understand how to recognize and manage these cannabis-associated visits. However, with research in this area still relatively young, emerging findings continue to offer fresh guidance. For instance, in one new study in Colorado, investigators found that while edible forms of cannabis make up only a small percentage of sales of cannabis products in that state, they are associated with more acute symptoms than the inhaled forms of the drug in patients who present to the ED. This is just one of several intriguing findings from a rich set of data that researchers are pouring over with the expectation they will unearth other important nuggets in the near future.

Treat the Symptoms

Patients with cannabis-related complaints comprise a small percentage of the overall population of patients who present to the ED at the University of Colorado Hospital in Aurora; however, providers here see such patients daily, according to Andrew Monte, MD, an associate professor of emergency medicine at the University of Colorado School of Medicine and an emergency physician in the hospital’s ED. “We are talking about one or two out of 300 patients every day,” he explains.

Most commonly, patients will present with symptoms of intoxication, but it is rarely just due to cannabis, Monte observes. “Usually, this will involve multiple drugs, of which cannabis is one,” he says.

Further, in patients who use cannabis heavily, providers see a lot of gastrointestinal (GI) symptoms, specifically a condition referred to as cannabinoid hyperemesis syndrome, which involves a cyclical vomiting condition. “The GI symptoms are the second most common symptom that [cannabis users] have” following cannabis intoxication, Monte says. However, Monte reiterates that it tends to occur only in patients who use cannabis every day or multiple times a day.

The third most common cannabis-related problem that brings people to the ED is acute psychiatric distress. “This may involve acute psychosis, acute anxiety, acute panic attacks, or even suicidality and depression,” Monte notes. Managing patients with cannabis-related problems typically involves treating the symptoms, Monte states.

“For example, in patients [who are] vomiting, we very often try anti-nausea medicines, although in patients with [cannabinoid hyperemesis syndrome], the anti-nausea medicines are not effective. We treat those patients with antipsychotics,” he explains. “That seems to be most effective, relatively low-dose antipsychotic medicines for the nausea.” Typically, patients who are vomiting frequently will receive fluids, Monte adds.

In patients with psychosis or anxiety, sedatives or benzodiazepines are administered to help them relax. “Then, sometimes, antipsychotics [are given] as well if patients are experiencing active hallucinations that are particularly problematic,” Monte notes.

Less commonly, patients who use cannabis will present with cardiovascular symptoms, such as cardiac ischemia, an arrhythmia, or even a heart attack, Monte explains. Consequently, he observes that patients exhibiting cardiovascular symptoms should receive an ECG. “You shouldn’t be blowing them off, thinking that it is just the pot,” he says. “They do need an ECG to make sure they don’t have cardiac ischemia or an arrhythmia.”

Note Impact of Edibles

Although most cannabis-related complaints are associated with inhaled versions of cannabis, new research by Monte and colleagues revealed that edible forms of cannabis are associated with more acute symptoms. In a review of ED visits that occurred between Jan. 1, 2012, and Dec. 31, 2016, researchers found there were 9,973 visits that were at least partially attributable to cannabis. Of these, 238 cases involved edible cannabis. However, researchers found these patients were nearly twice as likely (18% vs. 10.9%) to exhibit acute psychiatric symptoms vs. patients who inhaled cannabis. Further, patients who ingested edible cannabis were more than twice as likely (8% vs. 3.1%) to present with cardiovascular symptoms vs. patients who inhaled cannabis. On the other hand, GI symptoms were more prevalent in patients exposed to inhaled versions of cannabis (48% vs. 6.6%).1

Also, Monte and colleagues found that overall, cannabis-associated ED visits tripled during the study period, but that visits linked to edible forms of cannabis were 33 times higher than investigators expected, considering the fact that surveys suggest edible cannabis comprised only 0.3% of the total weight of tetrahydrocannabinol (THC), the primary active ingredient in cannabis, in cannabis product sales during this period.

Why would the edible forms of cannabis produce more intense or acute symptoms? Monte observes that investigators have not pinned down a precise answer, but he suspects that several factors are involved. For instance, Monte notes that when a cannabis product is ingested, the body metabolizes it so that the drug can cross the blood-brain barrier more effectively. Another potential factor involves the kinetics of the drug.

“Essentially, when someone smokes cannabis, they start to feel the effects right away. The symptoms peak in about 30 minutes. Then, [the drug] is cleared in two to three hours,” Monte explains. “However, when someone eats a cannabis product, it doesn’t even start to take effect until about a 30-minute period [has elapsed]. It doesn’t peak until two to three hours later, and then it can remain in the system for 12 hours.”

The delayed onset of the drug effect from an edible product provides more opportunity for someone to come to the ED if they are experiencing an adverse drug event, Monte suggests.

“If someone smokes cannabis, an [adverse effect] may only last a few minutes. Then, things settle down, they feel better, and may conclude they don’t need to go to the ED. But in someone who eats a cannabis edible, the effect may last hours. That puts them at risk to do something that they may regret, or just the symptoms may be so worrisome for so long that they will come to the ED.”

One other factor that may play a role: Considering that it takes longer to feel the effects of an edible cannabis product, people may consume more of the product, producing what Monte refers to as a stacking phenomenon.

Make the Diagnosis

From a clinical standpoint, providers cannot necessarily confirm that cannabis is the source of symptoms or illness. However, they can rule out other potential causes for symptoms, Monte observes. “We get pretty good at understanding and diagnosing based upon constellations of symptoms,” he says.

For instance, providers know that the cyclical vomiting syndrome occurs in people who smoke very heavily, and that patients will experience these episodes periodically. The history will help clinicians confirm the diagnosis in concert with workups that are negative, Monte explains.

Also, at least in Colorado, patients are very open about their use of cannabis, which is helpful in pinning down a diagnosis. “Cannabis is legal and it has been destigmatized for many, many years here now,” shares Monte. “Patients are fine with talking about it.”

Further, it is not difficult to distinguish intoxication from cannabis from that of alcohol or other drugs. For example, with alcohol intoxication, there tends to be far more issues with coordination, Monte notes.

“We can get some level of that with opioids as well because they are sedatives, but there is a very well-defined toxidrome [or distinguishing list] of what the symptoms are when people have actually taken too many opioids.”

Take a Good History

Monte’s advice to frontline providers in states that may be new to legalization, and are just beginning to see larger numbers of cannabis-associated ED visits, is to focus on taking a good history. For example, find out how often patients use cannabis, what types of products they use, and what percentage of THC the products contain. Secondly, develop an understanding of all the conditions that cannabis can cause, he says.

“Clearly, [cannabis] is associated with this cyclical vomiting syndrome in heavy users, and it is an intoxicating agent,” Monte reiterates. “It also doubles the risk of motor vehicle collisions. People need to understand that they shouldn’t be driving after utilizing [cannabis].”

Monte adds that both inhaled and edible cannabis products can cause hallucinations and acute psychiatric decompensation, facts worth considering when patients arrive with psychiatric exacerbations. “It is important to understand what their exposures are in order to potentially mitigate their symptoms going forward,” he says.

Further, stay tuned for new findings because there is much more to learn about cannabis in the coming months and years. Indeed, Monte suggests he and his research colleagues have only just begun to pull important information from a rich batch of pertinent data in Colorado. “There needs to be more characterization of the cardiovascular [symptoms], and there needs to be more characterization about neurologic conditions such as seizures,” Monte notes. “Many people believe cannabis can be an effective treatment for some seizure conditions. However … in our data set, we have several patients that have used large amounts of cannabis and have then had seizures.”

As more states move to legalize cannabis use, it is important to produce additional guidance so that medical providers are knowledgeable and prepared.

“When you get too much of something, it can be dangerous and cause adverse drug events,” Monte observes. “We just need to start to educate physicians as well as the public about what the risks are in order to help us mitigate some of those risks.”

REFERENCE

  1. Monte AA, Shelton SK, Mills E, et al. Acute illness associated with cannabis use, by route of exposure: An observational study. Ann Intern Med 2019;170:531-537.