A Last-Resort Drug for CHS: Case Report Finds Fosaprepitant Effective When Standard Antiemetics Fail
A new case report published in Cureus documents a successful use of fosaprepitant — a drug typically reserved for chemotherapy-induced nausea — in a patient with cannabinoid hyperemesis syndrome after all standard antiemetic treatments failed.
Authored by Markus D. Moore, Saeed K. Alzghari, and Andrew N. Soliman and published on August 19, 2025 (DOI: 10.7759/cureus.90477), the report contributes to a small but growing body of evidence suggesting that NK-1 receptor antagonists may offer a viable rescue option for patients with CHS who do not respond to conventional therapy.
Background: Why CHS is so difficult to treat
Cannabinoid hyperemesis syndrome is a condition that develops in people who have used cannabis heavily over a prolonged period — typically several years — and is defined by recurring, cyclical episodes of severe nausea, vomiting, and abdominal discomfort. These episodes tend to occur every few weeks to months, and symptoms fully subside only when cannabis use is discontinued entirely.
Cannabis interacts with cannabinoid (CB) receptors distributed throughout the central nervous system, including in the hypothalamus, hippocampus, cerebellum, and along the vagus nerve. Through its influence on the hypothalamus-pituitary-adrenal axis, THC affects a broad range of physiological processes — including the body’s vomiting reflex. The gastrointestinal tract is also densely populated with CB receptors and histamine receptors, both of which can trigger the emetic response when activated.
Repeated vomiting episodes in CHS carry serious medical consequences: progressive erosion of tooth enamel, dehydration, acute kidney injury, and potentially dangerous electrolyte disturbances that may require inpatient hospitalization.
Despite these risks, standard pharmacological options — IV fluids combined with antiemetics such as metoclopramide, ondansetron, promethazine, or prochlorperazine — are only partially effective at best. In a substantial subset of CHS patients, these medications provide little or no relief, leaving clinicians without clear alternatives.
The case: a patient with multiple comorbidities
The patient described in this report presented with a complex medical history including type 2 diabetes mellitus, hypertension, gastroparesis, and a seizure disorder. Prior to arriving at the emergency department, paramedics responded to her home and found her on the bathroom floor, actively vomiting. She received 25 mg of intravenous promethazine in the field, which produced only marginal improvement.
Upon arrival, she appeared pale and diaphoretic. She denied any recent trauma, recreational drug use, or alcohol consumption. She reported that similar vomiting episodes had been occurring repeatedly over the prior one to two months.
Initial laboratory workup was largely unremarkable, with one significant exception: her urine drug screen returned positive for tetrahydrocannabinol (THC). She disclosed to her care team that she had recently been discharged following a gastroparesis hospitalization and was currently taking an injectable GLP-1 receptor agonist (semaglutide). Her treating physician concluded that the intersection of chronic cannabis use, semaglutide therapy, and poorly controlled type 2 diabetes had collectively contributed to her pattern of cyclic vomiting.
When the antiemetics administered during her admission — similar in profile to those that had been tried in previous encounters — again failed to provide adequate relief, the clinical team made the decision to try fosaprepitant, an intravenous NK-1 receptor antagonist most commonly used in oncology settings to prevent chemotherapy-induced nausea and vomiting.
Fosaprepitant: a new option for refractory CHS?
Following administration of fosaprepitant, the patient’s nausea and vomiting resolved. She was clinically stable and was discharged in a timely manner.
The authors note that a prior published case described a similar clinical scenario, in which a CHS patient who failed multiple standard antiemetics was ultimately given oral aprepitant — the oral equivalent of fosaprepitant — as a final intervention. That patient also responded favorably and was discharged shortly after.
Together, these two cases suggest a consistent pattern: NK-1 receptor antagonists, whether delivered orally or intravenously, may be capable of interrupting the vomiting cascade in CHS when no other pharmacological approach has succeeded.
Conclusions and clinical implications
The authors conclude that fosaprepitant deserves consideration as a treatment option for patients hospitalized with refractory CHS. While the drug is not currently part of standard CHS management protocols, the evidence from this and related cases indicates it can provide meaningful relief when first- and second-line antiemetics are insufficient.
Importantly, the report underscores that fosaprepitant should be viewed as a bridge, not a cure. The only definitive resolution for CHS remains complete cessation of cannabis use. Clinicians managing CHS patients must continue to address the underlying use pattern alongside any acute pharmacological intervention.
As CHS becomes more prevalent — driven by wider cannabis access and increasingly potent products — expanding awareness of alternative treatment strategies among emergency medicine and inpatient providers is essential.
