Pharmacologic Treatment of Cannabinoid Hyperemesis Syndrome: A Systematic Review

First identified in 1990, the innate endocannabinoid system serves multiple endocrine functions, through the activation of receptors (principally CB1 and CB2) within the central nervous system, as well as in bones, the gastrointestinal tract, hepatocytes, pancreatic cells, muscles, uterus, and adipose cells. When exposed to low doses of cannabinoid, the activation of this system principally has an antiemetic effect. Within the gastrointestinal tract, this interaction inhibits the opening of the gastro-esophageal sphincter, slows peristalsis (through its action on smooth muscle cells), and lowers acid secretion [3, 4]. In the CNS, activation of these receptors has a direct role in regulating the sympathetic and hypothalamic-pituitary-adrenal axis, preventing overstimulation.

Cannabis Hyperemesis Syndrome (CHS)

Often recurrent, these frequent consultations add to the congestion of already chronically saturated emergency department(s) (ED). In order to curb this phenomenon, a specific approach for these patients is key, to enable appropriate treatment and long-term follow-up. Lorazepam has no studies assessing its utility in CHS, but a summary of case reports suggests an efficacy of 58.3% in 19 patients [3]. Despite the lack of evidence, clinical experience has led to lorazepam being recommended as an adjunct in recent cyclic vomiting syndrome guidelines for patients who have an anxiety component to their presentation [8].

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• We strive to reshape medical education and academia in their evolution beyond the traditional classroom.
• Examples of cannabinoids include tetrahydrocannabinol (THC) and cannabidiol (CBD).
• Bearing CHS and CWS in mind, patients who are chronic THC users presenting with hyperemesis and abdominal pain can have a multitude of other pathologies; Table 1 presents a non-exhaustive list of differential diagnoses illustrating the wide range of possibilities.
• This may include providing information about potential cognitive, psychiatric, and physical harms of cannabis use, plus clear patient-centric recommendations.

The San Diego Emergency Medicine Oversight Commission in collaboration with the County of San Diego Health and Human Services Agency and San Diego Kaiser Permanente Division of Medical Toxicology created an expert consensus panel to establish a guideline to unite the ED community in the treatment of CHS. Here is what pediatric health care providers need to know about this often debilitating disorder. Most people with CHS who stop using cannabis have relief from symptoms within 10 days. Researchers are currently studying several treatment options to manage the hyperemetic phase of CHS.

When should you consider cannabinoid hyperemesis syndrome as a diagnosis?

Importantly, for the definition of cyclic vomiting syndrome, these episodes of vomiting cannot be attributed to other disorders. This factor is a key distinguishing feature from cannabis hyperemesis syndrome, where the toxicokinetics of cannabis itself influence the course of the disease. Ultimately, the treatment of any illness is the removal of precipitating factors, not merely the management of its symptoms. The only definitive treatment of cannabis hyperemesis syndrome is the removal of cannabis exposure, which may ultimately require extensive coordination between the committed patient, an empathic and dedicated primary care physician, and appropriate substance use counseling and resources. An electrocardiogram may be useful to assess the patient’s QTc interval, especially in the context of antipsychotic medication use, as well as before the administration of certain antiemetics, which may prolong the QTc interval to extreme lengths.

Cannabinoid hyperemesis syndrome: public health implications and a novel model treatment guideline

CWS, on the other hand, tends to present in chronic users within 1–10 days after last THC intake, with a peak incidence between days 2 and 6. No correlation has been established between symptoms severity and quantity (of THC) previously consumed, and initial presentation (to acute care) tends to vary, with a clinical course not well defined. Symptoms, which include nausea and vomiting as well as psychological and other somatic issues, generally worsen the further the patient is from last consumption, and can last up to 4 weeks. This likely corresponds to the time needed for CB1 receptors to return to their original state in the central dopaminergic pathways; this important feature is key to long-term management of these patients, who require ambulatory follow-up rather than simple symptomatic relief [13]. A well-recognized association of symptoms, abdominal pain, and vomiting is, in chronic users, generally attributed to cannabinoid hyperemesis syndrome (CHS).

Cannabis use disorder (CUD) is the third most prevalent SUD with an estimated 22 million cases worldwide (following opioid use disorder at 26 million cases). We would like to acknowledge the work of Mrs. Chantal Briones, a community care nurse, who took the time to review with us the different therapeutic options and discuss long-term follow-up. Using the keywords “Cannabis,” “Hyperemesis,” “Syndrome,” “Withdrawal,” and “Emergency Medicine,” we performed an in-depth literature review of 3 electronic databases (PubMed®, Google scholar®, and Cochrane®), aimed at all articles containing any of the above keywords, until November 2021. We aim to disrupt how medical providers and trainees can gain public access to high-quality, educational content while also engaging in a dialogue about best-practices in EM and medical education.

Cannabinoid Hyperemesis Syndrome: Public Health Implications and a Novel Model Treatment Guideline

Like many EDs worldwide, the normalization of cannabis consumption has led to an increase in the number of cannabis-related consults in the ED (positive delta from 2.3 to 13.3 cases per 100,000 ED visits in the USA from 2006 to 2013) [43]. In light of the severity of their symptoms, cannabinoid hyperemesis syndrome these patients often require increased monitoring and accompaniment. With average ED times of 13.9 h [26], these patients, who often do not fill the criterion for hospitalization, are bound to already chronically oversaturated EDs and add to the pressure on healthcare systems.

• Distinguishing between these two pathologies is important as the underlying mechanism and treatment options differ.
• As highlighted by the public health opioid crisis, emergency physicians have a responsibility to prescribe opioids only for conditions where they would benefit patients.25 A novel CHS treatment guideline is presented to assist frontline clinicians with managing this increasingly common condition.
• In Switzerland, nearly 1/3 of the population over the age of 15 years has already tried cannabis for reasons other than medical purposes [2].
• In adult ED patients (over the age of 18) with moderate to severe alcohol withdrawal who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone.
• Working in a dose-dependent and biphasic manner, progressive desensitization of CB1 receptors can occur when overstimulated, creating paradoxical effects.
• Probably, a crucial factor in the genesis of CHS is the composition of cannabis.

Presentation to care during the prodromal or hyperemetic phases of CHS can prompt a variety of short- and long-term outcomes, from repeated ED visits with catastrophic sequelae to successful symptom control and patient-centric connection with long-term care. When pediatricians are aware, CHS symptoms can be the canary in the coal mine, leading patients to multidisciplinary support, insight, motivation, and long-term recovery. The only proven way to prevent cannabis hyperemesis syndrome is to avoid cannabis (marijuana). Treatment during the hyperemetic phase includes rehydration with bolus intravenous (IV) crystalloid fluids, IV dextrose-containing fluids (to arrest ketosis), correction of electrolyte abnormalities, and treatment of nausea (Table 2).

• Cannabis use disorder (CUD) is the third most prevalent SUD with an estimated 22 million cases worldwide (following opioid use disorder at 26 million cases).
• Cannabinoid hyperemesis syndrome (CHS) is a very unpleasant — and potentially dangerous — complication of long-term marijuana use.
• We lack high-grade evidence treatments specific to CHS, but essential management includes acute stabilization, longitudinal primary and mental health care to reduce harm of cannabis use, and serial reconsideration of diagnosis.

Haloperidol for treatment of cannabinoid hyperemesis syndrome