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Case Study

An anxious 28-year-old female patient arrives at your emergency department (ED) with severe nausea, vomiting and abdominal pain. This is her fifth visit in two months. In triage she reports her symptoms began at 10am and have continued for 6 hours without resolution. Her boyfriend says she only gets relief by taking long, hot baths or showers. Upon physical exam, she is afebrile with stable vital signs. Her abdomen is benign and laboratory values are within normal limits (WNL). Her earlier point-of-care ultrasound, CT scan, and workup were unremarkable. The patient reported long-term, chronic cannabis use during previous visits and has returned to the emergency room for symptomatic relief.  

Providers should consider cannabinoid hyperemesis in younger patients with a history of long-term cannabis use and recurrent episodes of nausea, vomiting, and abdominal pain. Cannabinoid hyperemesis syndrome (CHS) is a diagnosis of exclusion defined by three key characteristics: consistent and frequent use of marijuana over an extended duration, persistent episodes of severe nausea and vomiting that are resistant to standard anti-nausea treatments, and notable alleviation of symptoms when exposed to hot showers or baths [11]. Complete resolution of cannabis hyperemesis occurs with the cessation of cannabis use [11].  

Introduction   

Cannabis is the most cultivated, trafficked, and misused illegal drug worldwide with psychoactive and physiologic effects [1]. The term Cannabis refers to a variety of psychoactive substances derived from the Cannabis sativa plant. Delta 9-tetrahydrocannabinol (▵9_THC), the main psychoactive component in cannabis, is known to cause a range of pharmacological effects in both animals and humans [2].  

Tetrahydrocannabinol (THC) is a small lipophilic molecule along with over one hundred and fifteen cannabinoids identified which accumulates in the adipose tissue where it remains stored for extended periods of time [6][7]. The two primary receptors for cannabis are CB1, expressed through gastrointestinal (GI) symptoms, in which the drug reduces motility and sphincter tone, and CB2 found in the peripheral tissues [8].  

One explanation for cannabinoid hyperemesis syndrome is hyperstimulation of the CB1 receptor. The active compounds in cannabis–tetrahydrocannabinol (THC) can affect psychomotor behavior, mood, short-term memory impairment, thoughts, perceptions, intoxication, and anti‐emetic effects [3].  

Marijuana use disorder, where individuals struggle to control their use despite negative consequences, affects three in 10 users, and the risk increases with early use and frequency [16][17]. Moreover, extensive use of cannabis may heighten the likelihood of developing psychotic disorders [2].  

Medical literature identifies two syndromes related to the case scenario: cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS), both characterized by recurrent episodes of heavy nausea and vomiting [9]. For distinction, the features within (CVS), an underlying history of migraines, psychiatric comorbidities, and rapid gastric emptying exist [10].  

Statistical Evidence 

Concentrations of THC (part of marijuana that causes a high) has increased over the last 10 years, from 9.75% in 2009 to 13.88% in 2019 [12]. Between the years 2001-2002 and 2012-2013, the percentage of Americans who reported using marijuana more than doubled, coinciding with marijuana use disorder.  

A sizable portion of young adults in the United States use cannabis, according to the National Survey on Drug Use and Health. In 2021, over a third (35.4%) of young adults aged 18 to 25, representing 11.8 million people, reported using cannabis in the past year [4].  

During pregnancy, Cannabis sativa is the most used illicit drug. Studies have found that the self-reported rate of cannabis use among pregnant individuals varies between 2% and 5% [5].  

Definition 

Cannabinoid hyperemesis syndrome (CHS) is a constellation of symptoms characterized by chronic cannabis use leading to recurrent episodes of severe nausea and vomiting. Cannabinoid hyperemesis syndrome was first described as a phenomenon of increased marijuana use in 2004 [13].  

CHS is a rare condition affecting frequent, long-term users of cannabis (marijuana) characterized by a history of regular cannabis use, recurring episodes of severe nausea and vomiting often accompanied by vague and diffuse abdominal pain, compulsive hot bathing or showering, loss of appetite, weight loss, dehydration, headache, and fatigue occurring every few weeks to months [14].  

The exact cause of CHS is unknown, though research indicates the long-term effects of cannabinoids (the active compounds in cannabis) on the body’s endocannabinoid system, which regulates various functions including nausea, vomiting, and pain [15]. Resolution of symptoms after stopping cannabis use confirms the diagnosis. Patients with CHS often find temporary relief from symptoms by taking hot showers or baths [11].  

This syndrome is distinct because the nausea and vomiting are resistant to most traditional antiemetic (anti-nausea) therapies, and the symptoms persist until the cessation of cannabis [18]. Cannabinoid Hyperemesis Syndrome (CHS) is a recognized medical condition with multiple ongoing studies attempting to understand the underlying mechanisms. 

Pathophysiology  

The precise pathophysiology of CHS remains a subject of active research. The current leading hypothesis include endocannabinoid system dysregulation, capsaicin receptor (TRPV1) activation, gastrointestinal motility abnormalities, serotonergic system involvement, cannabinoid metabolite accumulation, and genetic predisposition [11][15][21][22].  

The Endocannabinoid System 

The endocannabinoid system (ECS) is known to play an essential role in the effects of cannabis on end organs [21]. Case studies and pre-clinical data indicate that THC, the main psychoactive compound in cannabis, disrupts the endocannabinoid system through its action on CB1 receptors [21]. This disruption affects several key systems, including stress and anxiety response, temperature regulation, the vanilloid pain system, and various neurotransmitter pathways [15]. These dysregulated systems are potential mechanisms behind the debilitating symptoms of CHS.  

Gastrointestinal System 

The chronic overstimulation of Cannabinoid receptors (CB1 and CB2) in the brain and gastrointestinal tract may disrupt the delicate balance of the endocannabinoid system [11]. Studies suggest that CHS might involve altered gut motility patterns through direct effects of cannabinoids on gastrointestinal smooth muscle or indirect effects through the endocannabinoid system, leading to delayed gastric emptying, and contributing to nausea and vomiting [15].  

Neurological System 

In addition, the CB1 receptor downregulation in specific brain regions could contribute to the cyclic nature of CHS [15]. Other potential mechanisms include Capsaicin Receptor (TRPV1) deactivation. Cannabis contains capsaicin-like compounds that activate TRPV1 receptors, which play a role in pain and temperature perception [19]. Prolonged exposure to cannabinoids inactivates TRPV1 resulting in central nausea, altered gastric motility, and abdominal pain [20].  

Serotonin is a neurotransmitter known to play a significant role in nausea and vomiting. Research suggests that CHS patients might have altered serotonin levels or receptor activity contributing to their symptoms [22].  

Storage in Fat 

Cannabinoid metabolites can accumulate in the bodies of CHS patients, although their specific role in the syndrome remains unclear. Research indicates that THC’s affinity for adipose tissue creates a reservoir, prolonging its effects and contributing to Cannabinoid Hyperemesis Syndrome (CHS).  

This “long-term storage” can lead to unexpected re-intoxication when stress or hunger triggers fat breakdown, releasing THC back into the bloodstream triggering the syndrome’s characteristic vomiting and nausea [23].  

THC is known to affect the hypothalamus, a region of the brain that regulates body temperature and digestive processes. Chronic THC exposure might disrupt the hypothalamic function, leading to the characteristic symptoms of CHS [24]. 

Genetic Factors 

There may be a genetic factor that makes certain individuals more susceptible to developing CHS. This could explain why only a subset of long-term cannabis users develop the syndrome. In the largest cohort of CHS patients analyzed to date (where mutations related to neurotransmitters, the endocannabinoid system, and the cytochrome P450 complex were involved in cannabinoid metabolism), there was a noted association between cannabis induced hyperemesis and a mutation observed in the intron of gene coding dopamine-2 receptor [31]. 

Stages of Cannabis Hyperemesis Syndrome 

The clinical course of cannabinoid hyperemesis syndrome occurs in three phases: prodromal, hyperemetic, and recovery phase. The hyperemetic phase ceases within 48 hours, and treatment involves supportive therapy with fluid resuscitation and anti-emetic medications. 

Prodromal Stage 

The prodromal stage has mild, nonspecific symptoms like nausea, abdominal discomfort, and anxiety. This stage can last for months or years before progressing [23].  

Hyperemesis Stage 

The hyperemesis stage is the most severe stage, characterized by recurrent episodes of intense nausea and vomiting. These episodes can last for hours or even days and may require hospitalization for hydration and treatment [23]. 

Recovery Stage 

The recovery stage occurs after stopping cannabis use and symptoms improve and resolve over time [23].  

Management/Treatment 

Supportive care and the cessation of cannabis are the primary treatments for the diagnosis of cannabis hyperemesis syndrome. Accompanying features of the diagnosis include age under fifty, weight loss, morning sickness, normal bowel patterns (no diarrhea), and an unremarkable diagnostic workup [25]. 

Once cannabis use ends, symptoms can resolve within 24-48 hours [15]. In severe cases, supportive care may include intravenous fluids, and medications for nausea and vomiting may be necessary [23]. It is important to note that CHS can recur if the patient resumes cannabis use. Therefore, long-term abstinence is crucial for managing the condition.  

If required, treatment in the ED involves fluid resuscitation and antiemetic medications. With ongoing emesis (two hours of heaving), providers can administer haloperidol 0.05mg/kg or 0.1mg/kg, superior to Ondansetron in clinical trials [26]. In patients receiving haloperidol, monitor for akathisia, dystonia, and rare sudden cardiac death secondary to QT prolongation [27].  

Complications 

Cannabis-induced hyperemesis syndrome, if left untreated, can cause several potential health complications including severe dehydration from the loss of fluids and electrolytes [14]. Electrolyte imbalances can lead to complications like muscle weakness, cramps, heart rhythm disturbances, and in severe cases, seizures [28]. Dehydration and electrolyte imbalances can impact the kidneys leading to acute kidney injury (AKI), a serious condition where the kidneys are unable to filter waste from the blood [29]. 

Violent nausea and vomiting can cause tearing of the delicate lining of the esophagus (Mallory-Weiss syndrome) producing significant chest pain and the potential for life-threatening bleeding [30]. The chronic nature of CHS can impact mental health, introducing anxiety, depression, and social isolation [14]. 

Conclusion

In the scenario of the 28-year-old female patient with a history of chronic cannabis use who presented to the ED on multiple occasions with severe nausea, vomiting, and abdominal pain, symptomology suggests cannabinoid hyperemesis syndrome.  

Symptom relief with hot baths or showers, normal investigative results, and the ineffectiveness of standard antiemetic treatments supports the diagnosis [9]. CHS is an under-recognized condition linked to long-term cannabis use, marked by cyclic episodes of nausea and vomiting, and abdominal discomfort [9]. Though pathophysiology remains complex, CHS involves the dysregulation of the endocannabinoid system and other physiological mechanisms.  

Awareness of CHS and its potential complications is crucial for effective treatment and prevention of long-term adverse effects. While medical cannabis can alleviate pain, nausea, and vomiting, its overuse can lead to complications in certain vulnerable and at-risk patients. Well-defined medicinal uses for cannabis do not negate the health complications for these individuals. The unwanted effects depend on the frequency and quantity of cannabis use. 

Management of CHS involves cessation of cannabis use and supportive care, with a focus on hydration and symptomatic relief. Given the rising prevalence of cannabis use and the increased potency of THC, healthcare providers should be vigilant about recognizing this condition in younger patients with a history of long-term cannabis use [32].  

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