High stakes: Considerations about cannabis

As more states legalize recreational and medical cannabis, hospitalists are finding themselves caring for regular users more frequently.

And not only is cannabis more accessible than ever, but the variety of ingestion routes and concentrations of tetrahydrocannabinol (THC)—the psychoactive cannabinoid in cannabis—are both increasing, potentially complicating inpatient care.

"What we're seeing is the isolation of THC as the cannabinoid of use," explained Susan Calcaterra, MD, MS, MPH, an addiction medicine physician and hospitalist at the University of Colorado Hospital in Aurora. "Before, people tended to smoke the flower, which has THC, cannabidiol, and around a hundred known cannabinoids in the product. But increasingly in Colorado, we're seeing people moving away from smoking the flower and using products containing pure THC."

Before the 1990s, cannabis THC concentrations hovered around 2%. In 2015, a chemical analysis of legal cannabis in Colorado found average concentrations of 18%, and 30% in some samples. "We know regular use of high THC-containing products is associated with adverse effects," Dr. Calcaterra said.

That risk, along with the fact that many patients use cannabis as part of their daily routines, underscores the importance of taking a detailed history of cannabis use in a nonjudgmental manner, whether patients present to the hospital with issues related to their drug use or other problems, according to experts.

What to say

To do this, hospitalists must be mindful of the language they use, said Srikar Jonna, MD, assistant professor of anesthesiology, critical care, and pain medicine at The University of Texas Health Science Center at Houston.

For recreational users, "giving the disclaimer that this question is being asked so that we can better tailor [their] medical care and that it's not being used to stigmatize or ostracize can be helpful in getting a patient to be more forthcoming," he said.

Thanks to decriminalization and legalization laws passing in many states, conversations on what was once a taboo topic have become more normalized.

"Most states have either legalized or decriminalized or at least have a cultural environment where cannabis is no longer heavily stigmatized," explained Charles Reznikoff, MD, FACP, an internal medicine physician and addiction specialist at Hennepin County Medical Center in Minneapolis. "For most states and environments, the clinician need only ask in a nonjudgmental way and to have an open-minded conversation with the patient. … I think they will find that patients are ready to talk about this."

Regular cannabis use can be a particular concern in some of hospitalists' typical patients, like the elderly and those with certain underlying conditions.

One recent review, published in PLoS One in February 2023, found that cannabis use was linked with greater frequencies of depression, cognitive impairment, anxiety, accidents and injuries, and acute health care use in patients ages 50 years and older.

"In older patients, anything that can inhibit the ability to think clearly can be a problem," said Jason Persoff, MD, a hospitalist at University of Colorado Hospital in Aurora.

Changes in body composition make seniors especially susceptible to the effects of cannabis. "THC is a fat-soluble substance and with increasing age, you have more body fat relative to water, which means that THC sticks around your system longer than it would when you were younger, so symptoms related to its use may last longer," explained Dr. Calcaterra.

Despite these risks, cannabis use among older adults rose by almost 50% between 2016 and 2018, according to research published by Annals of Internal Medicine in 2020.

Certain conditions also heighten risks associated with cannabis. Research presented at the 2023 American Heart Association Scientific Sessions found that cannabis use was linked with a 20% increased risk of an in-hospital major heart or brain event in patients with existing cardiovascular risk factors like hypertension, elevated cholesterol, or type 2 diabetes.

"While cannabis does not cause heart disease, it can exacerbate heart disease by causing vasodilation, a compensatory tachycardia, and orthostasis," said Dr. Reznikoff. "Someone who's having anginal symptoms, it would not be ideal to have them using cannabis, especially high-dose cannabis in that setting. … Cannabis can essentially cause coronary steal by creating vasodilation and exacerbate ischemic heart disease." Vasodilation and orthostasis can also predispose patients to falls.

One study published in the Journal of the American College of Cardiology in January 2020 estimated that more than 2 million Americans who reported in 2015-2016 that they currently use or have used cannabis had cardiovascular disease.

The drug carries a unique set of risks in the perioperative setting as well. "The risk of a heart attack after someone uses cannabis is five times higher if they have smoked it in the last hour prior to a stressor such as surgery," said Shalini Shah, MD, an anesthesiologist and pain management specialist at UCI Health in Orange, Calif. Dr. Shah is a coauthor of the American Society of Regional Anesthesia Pain Medicine's consensus guidelines on the management of perioperative patients on cannabis and cannabinoids, published in January 2023.

Certain conditions, like underlying heart disease, will increase that perioperative risk even further, Dr. Shah added. "This is why it's so important to ask patients if they have used cannabis."

Cannabis with other drugs

Several of the 100 cannabinoids in cannabis can have important drug-drug interactions. For example, cannabidiol, or CBD, is metabolized in the liver by P450 enzymes. For this reason, Dr. Reznikoff recommends hospitalists complete a P450 drug-drug interaction check with the patient's medicine list, especially for those taking high-dose oral CBD.

"I just use a standard internet search to remind myself what the P450 interactions are," he said.

Drugs like ketoconazole, itraconazole, ritonavir, and clarithromycin inhibit CYP3A4, the enzyme that metabolizes CBD. When any of these drugs are consumed with CBD, levels of CBD may increase. CBD may also raise serum concentrations of cyclosporine, sildenafil, antihistamines, haloperidol, and antiretrovirals, according to a review published by the Journal of General Internal Medicine in 2021.

In addition, some symptoms of cannabis use, like euphoria, somnolence, and increased appetite, can be compounded by other medications, for example, psychiatric drugs, said Dr. Jonna, who cowrote a paper on perioperative complications in patients with cannabis use disorder, published by JAMA Surgery in 2023.

On the other hand, those who are regular heavy cannabis users may experience withdrawal upon hospitalization and require medications for that.

Cannabis withdrawal is not life-threatening and usually doesn't carry serious medical consequences. But symptoms, including irritability, tremors, restlessness, insomnia, loss of appetite, headaches, and abdominal pain, among others, can be uncomfortable for patients.

"If someone is hospitalized or is postoperative and they're in cannabis withdrawal, that might create some clinical uncertainty about what's happening if they were to have these symptoms," explained Dr. Reznikoff. "It's important for clinicians to know the timeline of cannabis withdrawal and the symptoms, so that if these symptoms happen, they at least include cannabis withdrawal on their differential diagnosis."

Withdrawal can start around two days after abstinence and can last up to four weeks in chronic users.

To treat withdrawal, hospitalists could potentially prescribe dronabinol, a synthetic THC medication that's approved to treat nausea and vomiting in chemotherapy patients and to increase appetite in patients with HIV/AIDS. The drug is taken orally and comes in a capsule form of 10 mg, 2.5 mg, and 5 mg, as well as an oral solution of 5 mg/mL.

Its use for cannabis withdrawal is off-label. "Each hospital's pharmacy committee is going to probably want to review that," Dr. Reznikoff said. A dose of dronabinol will also not substitute for the THC a patient would take outside the hospital, but "giving typical doses of dronabinol to such a patient, it will make them feel a lot better," he said.

Off-label use of quetiapine and gabapentin may also help alleviate withdrawal symptoms, said Dr. Calcaterra, while Dr. Jonna noted that mirtazapine can help with insomnia and loss of appetite. Metoclopramide or promethazine can alleviate nausea, Dr. Calcaterra said.

Hospitalization due to cannabis

In many cases, cannabis is the reason patients present to the hospital in the first place.

Cannabis hyperemesis syndrome, which causes cyclical vomiting, nausea, and abdominal pain, is typically seen in frequent users, and rates of this condition are on the rise.

In one study carried out in Ontario, Canada, monthly ED visits for cannabis hyperemesis syndrome increased 13-fold between January 2014 and June 2021, and the rise was associated with market commercialization of cannabis. Findings were published by JAMA Network Open in September 2022.

Getting patients to accept that chronic cannabis use could be the root cause of their vomiting can be difficult.

"They believe and are entrenched in believing that [cannabis] is helping with their chronic nausea and vomiting when it's actually the cause of their chronic nausea and vomiting," explained Dr. Persoff. In these patients, it's crucial to get a full, detailed cannabis history, and be sure not to use stigmatizing language, he stressed.

Stopping cannabis use is the only way to get rid of the syndrome, but topical capsaicin can help relieve symptoms.

"We do see a lot [of] patients that come in with [cannabis hyperemesis syndrome]," said Dr. Calcaterra. Talking to these patients about their cannabis use and possibly using motivational interviewing "to hear if there is any room to change their behavior is really important, to get the patient on your side and try to maybe see how their use may be impacting their health," she said.

In addition to hyperemesis syndrome, hospitalists may see patients with acute cannabis intoxication. This is more common among infrequent users who do not have a tolerance to the drug. These patients can have a range of symptoms that oftentimes mimic other conditions.

If a patient comes in acting somnolent or is a little delirious, "you might be worried about things like sepsis," said Dr. Jonna. Cannabis can also cause tachycardia and nausea, leading clinicians to suspect cardiac diseases.

"We might be going down the wrong path in diagnosis if we think that someone has had acute intoxication with [cannabis] versus one of these other very serious conditions, too," Dr. Jonna cautioned.

Additional signs of acute intoxication include orthostatic hypotension, conjunctival injection, panic and anxiety, paranoia, and gait instability.

Treatment for acute intoxication includes supportive symptomatic care, like moving the patient to a quiet room with minimal stimulation. Additional care can target reduction of cannabis's adverse effects, said Dr. Calcaterra.

In-hospital use

The rise of cannabis use and confusion over the substance's legality means hospitalists may come across patients using the substance in the hospital. "Right now, it's happening a lot. It's probably happening under the radar," said Dr. Reznikoff.

Cannabis' classification as a Schedule I drug at the federal level while legal for recreational and medicinal purposes in several states puts hospitals and patients in a tricky position.

For the most part, hospital policies treat cannabis interchangeably with other federally illegal drugs, explained Dr. Reznikoff. Because most hospitals receive funding from CMS, they may be hesitant to condone use of a federally prohibited substance. "It's a very complicated issue," he said.

In-hospital use can be hard to monitor, especially when patients use vape pens or less obvious forms of ingestion. Some indicators of use are mild tachycardia or orthostatic hypotension, in addition to a change in mental status. As controlled substances typically aren't allowed in hospitals, security may confiscate patients' cannabis if it's found during their stay.

"Where we practice, at the University of Colorado in Aurora, Colorado, if nursing or security comes across [cannabis] products they are confiscated, even though it's legal in our state to use them recreationally," said Dr. Persoff. If this happens, "the first and most important thing is to reinforce the messaging that this is the local law or the current practice of the hospital and is not a judgment on the patient," he stressed.

In some cases, patients who feel they benefit from taking cannabis at home may experience a return of the symptoms they were medicating during their abstinence in the hospital.

"The commonest medicinal benefit people cite from cannabis use is help with sleep, and sleep is always poor in the hospital," said Dr. Reznikoff. "Being in tune to insomnia and helping your patients with insomnia is another tip for [care of] cannabis users who are hospitalized."

Cannabis's Schedule I classification also limits research on cannabis and related education of physicians, both of which experts think are needed. "Most studies examining the impact of cannabis use on various outcomes are observational [and] have heterogeneity in approaches taken for describing the cannabis-containing product used, the route of its use, and the concentration of THC in the product," explained Dr. Calcaterra.

In the meantime, recognizing that cannabis use is common, improving history taking to better tailor care, and normalizing cannabis consumption to ensure patients feel comfortable discussing their use are key.

"The biggest training issue is working [on] destigmatizing language to lower the barriers of helping patients feel connected to their clinicians, and understanding that we're not there to judge them," said Dr. Persoff. "Our job is not to judge them, but to help them make informed decisions."