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Pharmacology 101: Cannabinoid Hyperemesis Syndrome

Pharmacology 101 is an online column designed to keep EMS providers informed on formularies, dosages, effects, applications, and current research related to medications administered in the prehospital setting. If you have a medication-related question you’d like the author to address, contact editor@emsworld.com.

Marijuana is the most widely used drug in the world, with an estimated 183 million users (nearly 4% of the global population).1 Other statistics note that users over the age of 12 have been increasing, and one report found 49% of Americans said they had tried marijuana.2,3 Additionally, as states relax their legislation and marijuana becomes more widely used both for medical and recreational purposes, the adverse effects associated with acute and chronic use may become more prevalent. For example, one study in Colorado reported nearly double the number of emergency department visits for cyclic vomiting after liberalization of medical marijuana use.4

Cannabinoid Hyperemesis Syndrome

Cannabinoid hyperemesis syndrome (CHS) is characterized by the marijuana user experiencing severe cyclic nausea and vomiting (hyperemesis). This paradoxical hyperemetic effect can be confusing, as marijuana is known to be an antiemetic. Although marijuana has been used since the third millennium BC, CHS was only described for the first time in the medical literature in 2004—so why is it we’re only seeing cases of CHS now? At this time our understanding of CHS is still growing, and this is reflected in the fact that CHS may be underrecognized, and diagnosis may occur only after the patient undergoes repeated visits to the emergency department, hospitalizations, and expensive testing.3

The exact mechanisms of cannabinoid hyperemesis are unknown. Theories include chronic activation of cannabinoid receptors in the brain resulting in a paradoxical hyperemetic effect, the activation of receptors in the gut causing abdominal discomfort, and the increasing potency of cannabis over the years.3,5

Patients who present with CHS are typically younger (under 50 years) and ­long-term marijuana users. They will present with severe cyclical nausea and vomiting with abdominal pain. These signs and symptoms predictably occur in three phases: prodromal, hyperemetic, and recovery.

Prodromal—Patients will begin to experience nausea and vomiting that typically occurs in the morning. The sight and smell of food may induce nausea and may trigger a fear of vomiting. Abdominal pain may be present, and ironically, patients may increase their marijuana use at this stage in hopes it will relieve their nausea and vomiting.2,5

Hyperemetic—Patients will begin to experience nausea and vomiting with greater frequency (up to five times an hour), and weight loss may occur due to the incapacitating and overwhelming nature of the attacks. During this stage patients often discover that very hot showers or baths provide relief that is not found with antinausea medications like ondansetron or promethazine. Patients will learn the hottest showers provide the greatest relief and will sometimes stand under the shower until the hot water runs out or they’re scalded. This is a hallmark sign of CHS. During this stage patients also begin to seek care from healthcare providers, going to clinics and emergency departments an average of 15 times, with at least 1–2 hospital admissions.2,5

Recovery—Only when the patient stops using marijuana does the nausea and vomiting cease. Unfortunately the time to resolution of symptoms may take anywhere from a week to a month. Once the symptoms are resolved, using marijuana again will trigger symptoms—a compelling indication of the role of marijuana in CHS.2,5

Treatment

Scalding hot showers notwithstanding, pharmacological treatment options seem limited for CHS. The “usual” antiemetic drugs such as ondansetron, promethazine, prochlorperazine, and metoclopramide may be used but with limited relief.

Interestingly, topical capsaicin cream has been used with some success in patients with CHS. Capsaicin interacts with cannabinoid transient receptor potential vanilloid receptor 1 (TRPV1), which is also activated by temperature extremes. This is thought to be an explanation for both the capsaicin and the hot showers. The most common adverse effect with topical capsaicin cream is a burning sensation that may be intolerable to some patients.

A recent trial called Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC) found haloperidol to be superior to ondansetron for first-line treatment in marijuana users who present to the ED with active and ongoing vomiting. However, this was a small trial with a number of limitations, so its results should be interpreted carefully.6

Ultimately, the only truly definitive method for treating CHS is complete abstinence from marijuana. As mentioned previously, it may still take time for symptoms to abate once the patient ceases use. Patient education is essential once a diagnosis is made, as many patients believe marijuana use will relieve symptoms of nausea and vomiting and may be reluctant to abstain.

The views and opinions expressed in this article are those of the author and do not necessarily reflect those of the people, institutions, or organizations he has been, currently is, or will be affiliated with.

References

1. Richards JR. Cannabinoid Hyperemesis Syndrome: Pathophysiology and Treatment in the Emergency Department. J Emerg Med, 2018; 54(3): 354–63.

2. Lu MLRY, Agito MD. Cannabinoid hyperemesis syndrome: Marijuana is both antiemetic and proemetic. Cleve Clin J Med, 2015; 82(7): 429–34.

3. Khattar N, Routsolias JC. Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review. Am J Ther, 2018; 25(3): e357–e361.

4. Kim HS, Anderson JD, Saghafi O, Heard KJ, Monte AA. Cyclic vomiting presentations following marijuana liberalization in Colorado. Acad Emerg Med, 2015; 22(6): 694–9.

5. Pizarro-Osilla C. What Is Cannabinoid Hyperemesis Syndrome? J Emerg Nurs, 2018; 44(6): 665–7.

6. Ruberto AJ, Sivilotti MLA, Forrester S, Haet al. Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial. Ann Emerg Med, 2020 Nov 5; S0196-0644(20)30666-1 [epub ahead of print].

Daniel Hu, PharmD, BCCCP, has Doctor of Pharmacy degree and is a critical care and emergency medicine pharmacist. He is a frequent speaker at conferences and has many publications in peer-reviewed journals. 

Commentary from the EMS World Medical Director

Cannabinoid hyperemesis syndrome is only one of the diseases that can cause severe paroxysmal attacks of vomiting. As Dr. Hu says, it is even more challenging because some patients have traditionally treated nausea with cannabinoids. Cyclic vomiting syndrome, gastroparesis, pancreatitis, bowel obstructions, chemotherapy for cancer treatment, myocardial infarction and even elevated intracranial pressure from brain tumors can cause similar symptoms. In each of these, our traditional antiemetics may fail. Profound dehydration and its complications including renal failure may occur. 
 
From an EMS perspective, history of this and previous episodes, a physical exam, capillary blood glucose check, potentially a 12 lead EKG, and ultimately additional workup in the ED may be necessary for an accurate diagnosis and appropriate care. EMS treatment of the vomiting patient should include attention to the nausea, appropriate hydration and transport in a position of comfort. The history obtained by the EMS provider may be key to assuring accurate ED care and disposition of these challenging patients.
 
Michael W. Dailey, MD, FACEP, FAEMS, is Chief of Prehospital and Operational Medicine and Associate Professor of Emergency Medicine at Albany (N.Y.) Medical College.
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