CRx MAGAZINE

Summer 2020

Cannabinoid Hyperemesis Syndrome

Clinicians and patients must be aware of a rare consequence of chronic cannabis use.

Cannabinoid hyperemesis syndrome (also known as cannabis hyperemesis syndrome or CHS) is a recently identified, poorly understood condition associated with chronic, heavy use of cannabis. The serious phase of CHS is characterized by abdominal pain, nausea, and bouts of severe vomiting that may be relieved by taking hot showers or baths. However, it’s well established that the pain and vomiting (hyperemesis) stop only after complete abstinence from cannabis use (in all forms).

It’s not clear whether there are any noteworthy risk factors other than years of heavy, often daily cannabis use. Yet, there are plenty of examples of patients who use medical cannabis daily for years who don’t develop CHS. And while the prevalence appears to have increased rapidly since the condition was named, it’s possible that cases of CHS were misidentified for years.

Although CHS didn’t appear by name in medical literature until 2004, it’s likely that the condition had been around for much longer but had been identified as cyclic vomiting (CV). In both illnesses, patients present with repeated and severe bouts of vomiting.

And while CHS is rare, its prevalence appears to be on the rise with the legalization of medical and adult use of cannabis across the country. A group of physicians in Colorado looked at retrospective data to determine the prevalence of patients presenting with CV before and after the legalization of medical cannabis and describe the odds of marijuana use among CV visits in the same time period.1 In this study, they reviewed emergency department (ED) visits coded for CV. They found that the prevalence of CV presentations nearly doubled after the legalization of medical cannabis and that those patients were more likely to report frequent cannabis use. Thus, they conclude that many previous cases of CV may have been CHS.

The most significant difference between CV and CHS is that CHS is definitively treated by abstaining from all cannabis products.2 Unfortunately, because patients usually present in the ED with generalized abdominal pain, nausea, and vomiting and are often not truthful about cannabis use, diagnosis and treatment are delayed by extensive testing and pharmaceutical treatment of the symptoms.

Understanding the diagnostic criteria and having candid conversations with patients are the keys to uncovering the underlying cause of symptoms quickly and making it possible to provide at-home solutions for symptom management and long-term treatment.

Symptoms
Health care professionals divide the symptoms of CHS into the following three phases:

PHASE 1 | Prodromal
The first phase is characterized by early-morning nausea and abdominal pain, yet the patient is able to maintain normal eating patterns. At this point, regular users may try to use more cannabis in order to control the nausea. It’s possible for this phase to last months or years.

PHASE 2 | Hyperemetic
Symptoms during this phase include ongoing nausea, repeated episodes of intense vomiting, abdominal pain, and decreased food intake that may lead to dehydration and weight loss. In this phase, patients may find relief by taking hot showers multiple times a day. Sufferers usually seek medical care during this phase.

PHASE 3 | Recovery
Once cannabis use is completely discontinued, symptoms go away; normal eating and other daily activities resume. However, once a patient has experienced CHS, it’s likely that the symptoms will return quickly if cannabis is reintroduced.3

Diagnosis
From a clinical standpoint, CHS is a condition that leads to repeated and severe bouts of vomiting.3 Unfortunately, medical cannabis is often used to treat abdominal pain, nausea, and vomiting, which means the solution may worsen the condition it’s being used to treat—something that may be hard for medical users to appreciate. Because CHS has a generalized presentation, many health care professionals will order a series of tests to rule out other causes of vomiting. Tests can include benign blood tests for anemia, electrolytes, liver function, pancreatic enzymes, pregnancy, or drug use, and urine analyses. They may also include more invasive and expense tests such as X-rays, endoscopies, and head and abdominal CT scans. Because CHS is a relatively new diagnosis, health care professionals may not spot it, and as test results come back within normal ranges, it can take years for a patient to receive a CHS diagnosis. Not only is treatment delayed but also the patient cost can be significant. In one report, the median charge for diagnosis and treatment for CHS was more than $95,000 over two years.2

These challenges have led some EDs, especially in those states where cannabis is legal for both medical and adult use, to develop protocols for assessing patients who present with generalized nausea and vomiting symptoms for CV vs CHS.4

A systematic review revealed the following major diagnostic criteria in order of prevalence2:

  • severe nausea and vomiting (100%);
  • vomiting that recurs in a cyclic pattern over months (100%);
  • age less than 50 at time of evaluation (100%);
  • at least weekly cannabis use (97.4%);
  • resolution of symptoms after stopping cannabis use (96.8%);
  • compulsive hot baths/showers with symptom relief (92.3%);
  • abdominal pain (85.1%);
  • daily cannabis use (76.6%);
  • regular cannabis use for more than one year (74.8%); and
  • male predominance (72.9%).

While these are accepted as major diagnostic criteria, there’s no agreement about how many of these features are required for diagnosis. Those that overlap among different ED protocols for diagnosis include at least weekly cannabis use for greater than one year, severe nausea and vomiting that recur in cyclic patterns over months and are usually accompanied by abdominal pain, resolution of symptoms after cannabis cessation, and compulsive hot baths/showers with symptom relief. Even in states where medical cannabis is legal, it’s difficult for health care professionals to ascertain cannabis use. Studies have shown patients tend to deny or underreport drug use.5 Some EDs train their providers in motivational interviewing techniques that allow for brief interventions and identification of actual cannabis (or other substance) use. Motivational interviewing–based approaches include open-ended questions, affirmations, reflective listening, and summarizing.6 Combining the proposed diagnostic criteria with motivational interviewing techniques when patients present with generalized CV could save valuable time as well as money.

Pathophysiology
Much of what’s known about CHS is based on case studies, including some pertaining to CV. Moreover, because most CHS patients don’t agree to participate in follow-up programs, elucidating the pathophysiology is difficult and the occurrence of CHS in some long-term daily cannabis users and not others isn’t understood.7 Because the endocannabinoid system (ECS) is connected to gastrointestinal motility, appetite, and nausea/vomiting, dysregulation of the ECS may be the cause of CHS. One rat study suggests that chronic cannabinoid administration may elicit changes in expression of cannabinoid receptors within the stomach wall.8

While experts agree that more research is needed to uncover the precise cause of CHS, authors of a systematic review present the following two most studied hypotheses:

1. Long-term, daily use of cannabis causes cannabinoids to exaggeratedly bind to CB1 receptors in the gastrointestinal tract. This decreases gastrointestinal motility and gastric emptying, which may lead to hyperemesis.2
2. Chronic cannabis use leads to desensitization and downregulation of CB1 receptors that ordinarily have antiemetic effects that may cause rebound vomiting and pain. Cannabis cessation may allow for the recovery of CB1 receptor activity and relief from CHS symptoms.2

Treatment
The only definitive treatment identified for CHS is the discontinuation of cannabis use; the duration of abstinence that leads to symptom relief varies among patients and may be related to the length of time cannabis has been used chronically. In one small study of CHS ED visits (n=10), three patients didn’t abstain from cannabis use and continued to have symptoms, six patients stopped using cannabis and noted complete resolution of symptoms within one to three months, and one patient didn’t complete the follow-up program.9 Of note, absence of symptoms after ceasing cannabis use is considered by most health care professionals the key diagnostic criteria for CHS. Thus, tracking the true prevalence of CHS is difficult because patients rarely submit to follow-up visits.

There’s limited evidence for other supportive and symptomatic care for CHS patients. Secondary to severe vomiting and poor appetite, sufferers present with mild to moderate dehydration or acute renal failure that requires IV fluids and, possibly, a hospital admission.2 During hospitalization, other pharmaceuticals may be ordered to treat symptoms of pain and vomiting. In one case study, complete cessation of vomiting occurred in a CHS patient within one hour after administration of a dopamine antagonist.10 While opioids are often used for pain management, case study authors caution against using them because they’re associated with gastrointestinal dysfunction, which may worsen CHS symptoms, or worse, create opioid dependence.11

Most sufferers report finding relief from nausea and vomiting by taking warm or hot showers. At least one patient has reported spending four hours in a hot shower to get relief. There are anecdotal reports that rubbing capsaicin cream (0.025%) on the abdomen relieves the pain, nausea, and vomiting associated with CHS.12 Capsaicin cream is available as an over-the-counter treatment for arthritis. One study suggests that capsaicin exerts its effects via the TRVP-1 receptor, which is known to interact with the ECS.13

Clinical Applications
Research shows that chronic—daily and intermittent—cannabinoid administration may influence gastric motor function, leading to CHS in some people. Thus, it’s important to educate long-term therapeutic users to monitor and evaluate gastric discomfort and hyperemesis. Because severe, prolonged vomiting can lead to complications such as muscle spasms/weakness, seizures, kidney failure, or heart rhythm abnormalities, it’s important for therapeutic users to seek medical treatment and be honest about cannabis use if they suspect CHS.

At-home treatment is possible in the early (prodromal) stage of CHS. First and foremost, patients should take a cannabis holiday, which means discontinuing use for at least one week. While this may seem counterintuitive to patients, especially those who have been using cannabis to control abdominal pain, nausea, or vomiting for years, it’s the fastest way to confirm the diagnosis and eliminate symptoms. Second, hot showers provide relief but aren’t a first line of defense; they may only prolong symptoms if cannabis use continues. Last, some studies suggest that over-the-counter capsaicin cream (0.025%) may be used to treat abdominal pain, nausea, and vomiting because it mimics the action of a hot shower. Patients should be counseled that it may cause an uncomfortable burning sensation at first and to keep the cream away from the face, eyes, genitourinary region, and other areas of sensitive or broken skin. Finally, as with hot showers, capsaicin cream isn’t a replacement for cannabis abstinence.

Keep in mind that CHS doesn’t affect every chronic therapeutic cannabis user. It’s still considered very rare. For patients concerned about reports of increasing prevalence of CHS, they can be assured that some of the rise in reports is because health care professionals are becoming more aware of the condition. Working with a cannabis practitioner can reduce the prevalence through awareness and education.

— Bonnie Johnson, MS, RDN, HCP, is a registered dietitian nutritionist, food industry consultant, speaker, and certified cannabis consultant. She spends much of her volunteer time educating a variety of audiences about the benefits and potential risks of using cannabis to treat chronic pain, anxiety, insomnia, and other ailments. As a consultant, she works with the food and cannabis industries to bring science-based education to health care professionals and category-changing products to market.

References

1. Kim HS, Anderson JD, Saghafi O, Heard KJ, Monte AA. Cyclic vomiting presentations following marijuana liberalization in Colorado. Acad Emerg Med. 2015;22(6):694-699.

2. 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.

3. Cannabinoid hyperemesis syndrome. Cedars-Sinai website. https://www.cedars-sinai.org/health-library/diseases-and-conditions/c/cannabinoid-hyperemesis-syndrome.html. Accessed March 28, 2020.

4. Lapoint J, Meyer S, Yu CK, et al. Cannabinoid hyperemesis syndrome: public health implications and a novel model treatment guideline. West J Emerg Med. 2018;19(2):380-386.

5. Rockett I, Putnam S, Jia H, Smith G. Declared and undeclared substance use among emergency department patients: a population-based study. Addiction. 2006;101(5):706-712.

6. Hawk K, D’Onofrio G. Emergency department screening and interventions for substance use disorders. Addict Sci Clin Pract. 2019;14(1):26.

7. Perrotta G, Miller J, Stevens T, et al. Cannabinoid hyperemesis: relevance to emergency medicine. Acad Emerg Med. 2012;19:S286-S2S7.

8. Abalo R, Vera G, López-Pérez AE, Martínez-Villaluenga M, Martín-Fontelles MI. The gastrointestinal pharmacology of cannabinoids: focus on motility. Pharmacology. 2012;90(1-2):1-10.

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

10. Hickey JL, Witsil JC, Mycyk MB. Haloperidol for treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med. 2013;31(6):1003.e5-1003.e6.

11. Galli JA, Sawaya RA, Friedenberg FK. Cannabinoid hyperemesis syndrome. Curr Drug Abuse Rev. 2011;4(4):241-249.

12. Graham J, Barberio M, Wang GS. Capsaicin cream for treatment of cannabinoid hyperemesis syndrome in adolescents: a case series. Pediatrics. 2017;140(6):e20163795.

13. Rudd JA, Nalivaiko E, Matsuki N, Wan C, Andrews PL. The involvement of TRPV1 in emesis and anti-emesis. Temperature (Austin). 2015;2(2):258-276.

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