Cannabinoid hyperemesis syndrome (CHS) is a condition that gastroenterologists are increasingly encountering in both the inpatient and outpatient setting. A survey conducted in the United States found that approximately 8.4% of the population aged 12 or older were current cannabis users.1 As the laws surrounding cannabis use continue to evolve, more people will undoubtedly be exposed to cannabis. In addition to recreational use, cannabis is frequently used as an adjunctive treatment in multiple conditions including chemotherapy-induced nausea and vomiting, chronic pain, lack of appetite, and depression.2  

As more people are exposed to cannabis, new clinical entities will undoubtedly evolve. One such diagnosis is CHS, where patients develop cyclic vomiting in the setting of chronic cannabis use.3 Classically, patients with CHS frequently report relief of nausea and vomiting when they take hot baths or showers. 

CHS can be challenging to diagnose based on multiple factors. There can be a certain stigma associated with cannabis use, along with potential legal ramifications in certain parts of the United States. This can make patients wary to disclose their cannabis use and can make physicians hesitant to ask for a detailed history. Cannabis is available in numerous formulations; therefore, standardizing the dosing is extremely challenging. Even if a detailed history is elicited by a physician, the lack of formal diagnostic criteria can make the diagnosis relatively subjective. This makes the real-time diagnosis difficult, while at the same time complicating formal clinical research studies. 

Although formal diagnostic criteria are not available, CHS appears to be relatively common in the real world. One United States-based retrospective study of 1571 found that CHS affects up to 6% of those who were evaluated for recurrent vomiting in the emergency department.4 


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Based on the lack of formal diagnostic criteria, many patients with CHS will undergo an extensive evaluation including laboratory work, imaging, and endoscopic procedures such as esophagogastroduodenoscopy.3 When first evaluating a patient for CHS, it is reasonable to start with basic laboratory work such as a complete blood count, comprehensive metabolic panel, hemoglobin A1c, and thyroid function tests. Depending on the history and physical, additional studies to consider include abdominal ultrasound, contrast enhanced computed tomography or magnetic resonance imaging of the abdomen, a gastric emptying scan, and imaging of the brain to rule out central causes. 

As expected, a complete and thorough workup can be both time and cost exhaustive. In addition to the expenses associated with the diagnostic testing, there is also a significant economic burden in the setting of frequent primary care, specialist and emergency room visits, and medication trials.5 An observational study found that the median charge for emergency department visits and hospital admissions was over $95,000.5 

In attempts to further clarify formal diagnostic criteria, researchers published a systemic review in the Journal of Medical Toxicology that included 170 publications, although the overall quality of the articles was low which precluded a formal meta-analysis.3 The studies were relatively heterogeneous, but there was significant overlap between certain diagnostic characteristics among the publications. Of the studies evaluated, the overlapping diagnostic findings included a history of regular cannabis uses for more than 1 year (74.8%), severe nausea and vomiting (100%), vomiting in a cyclical pattern over months (100%), compulsive hot showers/baths with symptom relief (92.3%), resolution of symptoms after cannabis discontinuation (96.8%), being a man (72.9%), abdominal pain (85.1%), at least weekly cannabis use (97.4%), and age less than 50 at time of evaluation (100%).3 Therefore, when evaluating a patient for potential CHS, it is critical to obtain the frequency and duration of any cannabis use.

The systematic analysis conducted by the authors yielded a total of 211 patients with CHS. Investigators found that the median ages associated with CHS benchmarks occurred before age 30, with a median age of onset of cannabis use of 16 years, a median age at symptom onset of 24 years, and a median age at diagnosis of 28 years (interquartile range 14-18, 19-29, and 22-34, respectively).3 The mean delay of symptom onset to CHS diagnosis was 4.1±4.6 years. These data indicate that CHS is both under-recognized and underdiagnosed. Researchers also found that 36.3% of patients used cannabis for 2 to 5 years and 25.1% used cannabis for <1 year prior to symptom onset. The frequency of cannabis use was reported as daily use in 47.9% of patients, while 23.7% reported greater than daily use.3

The pathophysiology of CHS is not entirely understood and is most likely multifactorial. Potential mechanisms include the dysregulation of the endocannabinoid system with its downstream effects of decreased gastrointestinal motility including delayed gastric emptying, desensitization and downregulation of the normally antiemetic cannabinoid receptors, and dilation of the splanchnic vasculature.3 The relief that hot baths and showers provide does support the role of the latter, as peripheral vasodilation and consequential shunting of blood away from the splanchnic vasculature may lead to reduced symptoms.3 In addition to these factors, other pathophysiologic factors such as enzymatic breakdown and genetic predispositions may also play a significant role.3 

The only reliable treatment identified in the systematic review was cessation of cannabis use.3 If patients are able to tolerate the discontinuation of cannabis, it may take up to 2 weeks before the patient reports relief, which can make this therapeutic option challenging.6 There were mixed data on topical capsaicin and dopamine antagonists, including haloperidol. Topical capsaicin is relatively inexpensive, available over-the-counter, and offers a therapeutic option to patients who may not be able to tolerate oral medications. Capsaicin cream may help patients with CHS by activating the transient receptor potential vanilloid subtype 1, which plays a role in the endocannabinoid system.6 

Physicians should consider limiting treatment with opioids as this may further alter the patient’s gastrointestinal motility and predispose to opioid dependence, especially with repeat evaluations and admissions. Supportive care with intravenous fluid and other anti-emetics are often administered; however, the definite clinical impact is not known. Benzodiazepines are also frequently administered to patients with CHS based on their antiemetic and anxiolytic properties, but these agents are better suited for acute management vs long-term treatments based on their side effect profile.6 

As with many studies evaluating CHS, the systematic review was limited by the heterogeneity of the studies included.3 However, this review was still a useful study attempting to clarify more thoroughly researched diagnostic criteria. The authors concluded that key characteristics of CHS include severe cyclic nausea and vomiting usually accompanied by abdominal pain, symptom onset preceded by at least weekly cannabis use, temporary relief with hot showers, and resolution of symptoms with cessation of cannabis use. In addition to these characteristics, other factors that supported the diagnosis of CHS included the onset of cannabis use in the teenage years, symptom onset in the third decade of life, and a predisposition toward the male gender.3 

CHS will continue to be a diagnostic challenge now and in the future. More formal clinical studies are needed in order to further clarify diagnostic criteria and the best acute and chronic treatment options. Gastroenterologists will have to continue to balance the risks and benefits of ordering a multitude of diagnostic tests when CHS is suspected. Meanwhile, attempting to limit the perceived stigma of inquiring about cannabis use may be crucial to obtaining a thorough and accurate history from the patient. 

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References

1.     Hedden SL, Kennet J, Lipari R, et al. Substance Abuse and Mental Health Services Administration. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health.   https://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf. Published September 2015. Accessed August 18, 2020.

2.     Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456-2473.

3.     Sorensen CJ, DeSanto K, Borgelt L, Phillips KT, Monte AA. Cannabinoid hyperemesis syndrome: diagnosis, pathophysiology, and treatment—a systematic review. J Med Toxicol. 2017;13(1):71-87.

4.     Simonetto DA, Oxentenko AS, Herman ML, Szostek JH. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc. 2012;87(2):114-119.

5.     Perrotta G, Miller J, Stevens T, et al. Cannabinoid hyperemesis: relevance to emergency medicine. Presented at: Society for Academic Emergency Medicine Annual Meeting; Chicago, IL; May 9-12, 2012. Abstract 542. 2012;19:S286-S287.

6.     Chocron Y, Zuber JP, Vaucher J. Cannabinoid hyperemesis syndrome. BMJ. 2019;366:I4336.