Expanding recreational access to plant-based and synthetic cannabis is causing concern amongst emergency room (ER) doctors across the country, who say that they are seeing increasing numbers of patients presenting with cannabinoid hyperemesis syndrome (CHS).

The condition, which is characterized by severe nausea, prolonged and heavy vomiting, and diffuse abdominal pain and tenderness, appears to occur among consistent heavy cannabis users who consume as much as 4 g daily over a year or more.

Cross-sectional data from numerous studies, including one published late last year, appear to support the dangerous intersection of regular use of higher potency products and recreational access and the rise in cases presenting to the ER. However, CHS has no standard diagnosis, differentials, tests, or consensus on evidence-based treatment, which may indicate an overestimation of case numbers and/or misdiagnosis, further challenging management.

It can be a frustrating condition, ER doctors who encounter these patients told Medscape Medical News.

“It is a little difficult to diagnose because we don’t have a specific test or biomarker; it’s a diagnosis of exclusion,” said Andrew C. Meltzer, MD, professor of emergency medicine at George Washington University in Washington, DC.

“I think that there’s a danger of anchoring on this and missing other diseases; sometimes a colleague will tell me that they’ve seen three of these cases and then the next one looks similar. It turns out they’ve missed something else that was significant, for example, pancreatitis cancer or gastric ulcer,” he said.

CHS is believed to be a form of cyclical vomiting, “which tends not to have an underlying cause,” said Sam Torbati, MD, chair of emergency medicine at Cedars-Sinai Medical Center in Los Angeles. “With CHS, cannabinoids are triggering it and differentiation can be impossible unless patients tell you about their habit.”

Causation vs Correlation

CHS was first reported in nine patients by an Australian family physician over 20 years ago, but the first known index case dated back to 1996. Cannabinoids have a biphasic dose-response effect; in small doses, tetrahydrocannabinol (THC), the primary psychoactive component in cannabis display anti-emetic properties (and has been used to relieve nausea and vomiting in patients receiving cancer chemotherapy) but in high doses, becomes pro-emetic.

“Many people like to say that CHS is due to toxic exposure to pesticides or NEEM in the cannabis plant, but there’s no foundation for that,” said Ethan Russo, MD, neurologist, psychopharmacology researcher, and founder and CEO of Credo-Science, a research and development company dedicated to making cannabis safer. He also disputed the hypothesis that CHS is a form of CVS, which he said most commonly appears in infancy or childhood and is an atypical manifestation of migraine.

“We have to provide an explanation for why some people use huge amounts of cannabis and never develop CHS vs those who do,” said Russo. “Several years ago, I hypothesized there could be a genetic susceptibility.”

It might be the case.

In a small study among CHS diagnosed and never diagnosed heavy cannabis users who agreed to undergo genetic testing, Russo identified mutations in several genetic receptors involved with heat/pain responses, THC metabolism, dopamine metabolism/susceptibility to addiction, depression and other psychiatric issues, and ironically, cholesterol regulation.

Despite regular, heavy cannabis use exceeding 4 g daily, only individuals with some or all of these mutations had received a physician diagnosis of CHS, while the control individuals with similar consumption patterns received neither a diagnosis or experienced vomiting, nausea, and abdominal pain.

Thangam Venkatesan, MD, professor of medicine in the Division of Gastroenterology, Hepatology, and Nutrition at Ohio State University Wexner Medical Center in Columbus, Ohio, said that she agrees with Russo that there is likely a genetic component. But her clinical and research experience in both CVS and cannabinoids has led in another direction.

“I think that there’s probably a small subset of patients where cannabis can unmask symptoms or lead to vomiting,” she said. But “CHS is probably a subset of CVS.”

“I have patients who stop cannabis and it doesn’t go away. And I have patients who continue to use cannabis, and I treat them like I treat CVS and their symptoms improve,” she said. The problem, she noted, is that thus far, studies have not met what she considered the bar for providing clear evidence one way or the other.

Patient Denial Is Real

Many patients with CHS are reluctant to discuss their cannabis use or consider that symptoms are associated with cannabis. This hesitancy makes differential diagnosis difficult and is often a harbinger for ongoing ER visits.

“Management of these patients is predominantly based on their pattern, how much information they offer, how honest they are, and how much previous testing they’ve done,” said Torbati, also noting that it’s not unusual for CHS patients to visit hospitals that don’t have electronic medical records that connect to other hospitals in order to hide their condition.

“When patients don’t tell us what their history is (and unfortunately, a lot of patients with this condition), it’s hard to minimize testing and focus on treatment,” he said.

“There are many situations of a young person going to the ER, being asked about vomiting and abdominal pain and if they use cannabis. The doctor only has a few minutes to talk to them,” said Russo. “This is not a situation that is amenable to sorting things out in a few minutes.”

“A lot of cannabis user who develop CHS, don’t necessarily believe it’s the cannabis causing their symptoms,” said Joshua Ring, MD, an emergency medicine and pediatric emergency medicine physician at Duke Regional Hospital in Durham, North Carolina. “People have told me they’ve been smoking for years and have never had a problem. Other times, cannabis might make them feel better and help their nausea for a bit and then a few hours later, they start vomiting again,” said Ring.

“I’ve never in my career experienced a group of patients that has resisted diagnosis as much as this group, I think it is really part of the condition,” said Russo.

Meltzer noted the impact on lives is significant.

“What’s really striking is how people really can’t go back to work, they can’t function, they can’t take care of their kids, they’re driving up medical bills by getting all of these tests and seeing all of these doctors,” he said.

Moving Past the Acute Event

Currently, acute CHS treatment strategies include haloperidol to stop vomiting and address anxiety that might be exacerbating vomiting (benzodiazepines might also be helpful for the latter), hot baths or showers, topical capsaicin, and fluids to relieve dehydration.

Like many substance abuse issues, CHS requires time to treat and help patients sustain. But unlike other substance conditions, it does not have an identifiable target to help facilitate and maintain cessation. For now, the only management tool shown to be effective is abstinence.

“We need to figure out how to connect with these patients and gain their trust; the more they trust us, the more likely it is that they will hear us and engage in what it takes for their recovery,” said Torbati.

The key, said Meltzer “is to ask questions without judgement and emphasize empathy.”

“For most people, it’s one of the worst days of the year. I hate to take advantage of a crisis, but perhaps this is a time when patients might be a little more receptive to being reminded that there’s another way to deal with this.”

Torbati, Meltzer, Venkatesan, and Ring reported having no financial disclosures of interest. Russo reported being the founder and CEO of Credo-Science.Com.

Liz Scherer is an independent health and medical journalist. She frequently writes about cannabinoids and cannabis.