CANNABINOID HYPEREMESIS SYNDROME

But they are in fact classic signs of cannabinoid hyperemesis syndrome (CHS), a puzzling gastrointestinal condition that’s associated with frequent, long-term use of marijuana.

First described in 2004 by doctors in Australia, CHS affects an estimated 2.75 million people in the U.S. each year, and cases are rising: According to research in an October 2024 issue of JAMA, emergency department visits related to CHS doubled in the U.S. and Canada from 2017 to 2021.

(Do you smoke weed recreationally? Here’s what experts want you to know.)

What’s behind the rise? It may be partly because marijuana is now easier to access, thanks to the broadening legalization of cannabis for recreational use. Research supports this notion. In a 2024 study published in the Journal of Clinical Gastroenterology, researchers compared hospitalizations for CHS at a large hospital in Massachusetts in 2012 and 2021, before and after cannabis was legalized in the state: They found a significant increase in hospitalizations.

Another factor: “The cannabis that’s available now is much more potent than what was available 30 years ago,” says Deepak Cyril D’Souza, a professor of psychiatry at the Yale University School of Medicine and director of the Yale Center for the Science of Cannabis and Cannabinoids. In the 1960s, the potency of delta-9-tetrahydrocannabinol (THC), the psychotropic component in marijuana, was typically 2 to 4 percent, D’Souza notes, whereas these days the concentration of THC can be 18 to 35 percent or higher.

Still “why some people seem to be vulnerable to this and not others really seems to be a mystery,” says D’Souza. Here’s what researchers are unraveling about this curious condition.

Who’s at risk and why

The biggest risk factor for CHS is heavy cannabis use, as in almost daily or multiple times per day over several years. People can develop the syndrome at any time, even after decades of prolonged use of cannabis.

That said, “most people who smoke cannabis daily don’t get this,” says Christopher N. Andrews, a clinical professor of gastroenterology at the University of Calgary. Among those who do, it isn’t a constant affliction. “It comes and goes and it happens in cycles,” says D’Souza. “If it continued indefinitely, that would force a person to stop” using cannabis.

(Indica vs. sativa: Science suggests there’s not actually a difference.)

In a 2019 review of 271 cases, researchers found that the mean age for having CHS was 30 and that 69 percent of people were male. They also found that daily use occurred in 68 percent of people with the syndrome, and the mean duration of cannabis use before the onset of CHS was 6.6 years. 

So what might make some people more susceptible? D’Souza speculates that it may have to do with some people’s endocannabinoid systems.

The human body has an endogenous (internal) cannabinoid system that regulates many critical bodily functions, including learning and memory, pain perception, and immune function. It’s comprised of cannabinoid receptors (mainly in the brain and throughout the gut) that respond to signals from the body, as well as compounds known as endogenous cannabinoids that are similar to those found in the cannabis plant.

CHS may be related to an imbalance in the body’s communication system—the hypothalamic-pituitary-adrenal (HPA) axis—which regulates stress responses,” says Andrews. “The [brain’s] endocannabinoid system modulates the stress response, and cannabis makes that pendulum swing further one way than the other,” which can trigger symptoms.

There also may be a genetic susceptibility to CHS, and depression and anxiety are common in people with the syndrome. “The paradox of this is we don’t understand what’s triggering this in a particular moment,” says David Levinthal, director of the Neurogastroenterology and Motility Center at the University of Pittsburgh Medical Center. Among the leading suspects, he says, are lack of sleep and intense stress. 

The symptom patterns associated with CHS are similar to cyclic vomiting syndrome (CVS), a chronic disorder related to gut-brain interaction that’s characterized by recurrent episodes of nausea, vomiting, and dry heaving, separated by symptom-free periods in between.

(What is cyclic vomiting syndrome and how is it diagnosed?)

The biggest difference between the two syndromes: It’s chronic cannabis use that triggers flareups of CHS. “There’s a debate about whether cannabinoid hyperemesis syndrome is a subset of cyclic vomiting syndrome with a different trigger,” says Levinthal.

Regardless of how it’s classified, “this can be a severe condition that can cause complications if it’s not treated,” says Maria Isabel Angulo, an assistant professor of internal medicine and pediatrics at the University of Illinois in Chicago. Complications can include severe dehydration and electrolyte imbalances, which can lead to kidney injury, heart rhythm abnormalities, and seizures. In addition, frequent vomiting from any cause can lead to erosion of tooth enamel and potentially tooth loss, she adds. 

Diagnosis and treatment

The criteria for diagnosing CHS includes having three or more episodes of nausea, vomiting, and abdominal pain in a year, with each episode lasting less than a week; using cannabis more than four days per week for more than a year; and having symptoms resolve after quitting cannabis for at least six months, according to the AGA.

“The way to make the diagnosis is to come off cannabis, proving retrospectively that it’s the cannabis [that was causing the symptoms],” Andrews explains. Because it requires many months of abstinence to diagnose CHS, some chronic cannabis users are reluctant to go down that path, experts say. 

When CHS flare-ups occur and the vomiting is profuse, people can become dehydrated, which is why they should seek urgent medical care. That way, they can receive intravenous fluids (with electrolytes) and anti-emetics drugs (anti-nausea medications such as ondansetron, promethazine, or prochlorperazine) to stop the vomiting. In other instances, they may be given a benzodiazepine (such as alprazolam) or an antipsychotic medication (such as haloperidol) to try to stop an episode in its tracks. 

During a flare-up, people with CHS also often take hot baths or showers, sometimes multiple times per day, to try to relieve their discomfort. “People with CHS often report temporary relief of symptoms from bathing in hot water, which may lead to compulsive bathing,” Angulo says. This suggests that the area of the brain that’s involved in regulating body temperature—the hypothalamus—might be involved in CHS, D’Souza says.

A lesser known intervention: Application of topical capsaicin (0.1%) cream to the upper abdomen can reduce nausea and vomiting associated with CHS. A study in the journal Academic Emergency Medicine found that when people with nausea and vomiting due to CHS were treated with capsaicin cream, they experienced a significant reduction in nausea within an hour.

So far, giving up cannabis has been shown to be the only long-term solution. But quitting cold turkey can lead to cannabis withdrawal symptoms such as anxiety, irritability, anger, sleep disturbances, depressed mood, and loss of appetite. Working with a counselor and taking a tricyclic antidepressant (such as amitriptyline) “can help with marijuana cessation,” Angulo says. Another option is to slowly taper off use of THC.

For people who can’t contemplate quitting, “other ways to improve symptoms [of CHS] are to reduce cannabis use and to stop using concentrates,” says Andrews. He adds that people might also switch to a more balanced formulation of THC and other cannabinoids such as cannabidiol (CBD), which does not cause a “high” sensation; these hybrid formulations are less potent.

Meanwhile, scientists are continuing to explore the mechanisms behind this mysterious condition and how it can be better treated. “Clearly, we need to study this more,” D’Souza says.