Two adolescents with cannabinoid hyperemesis syndrome who didn't respond to standard treatments for 36–45 hours experienced rapid resolution of vomiting within 1 hour of receiving aprepitant.
Emergency physicians treating CHS, pediatric gastroenterologists, and heavy cannabis users who experience cyclic vomiting.
What the researchers found
Cannabinoid hyperemesis syndrome (CHS) vomiting can be agonizing and resistant to standard antiemetics. This case report describes two teenagers with CHS who failed to improve despite 36–45 hours of ondansetron, metoclopramide, haloperidol, and capsaicin—the usual CHS treatment toolkit.
Then they received aprepitant, a neurokinin-1 (NK1) receptor antagonist originally developed for chemotherapy-induced nausea. The response was dramatic: vomiting stopped within 1 hour, oral fluids were tolerated within 1–2 hours, solid food within 4–8 hours, and both patients were discharged the following day without needing additional antiemetics.
The speed and completeness of the response is striking. After nearly two days of failed conventional treatment, a single dose of aprepitant resolved the acute episode. While cannabis cessation remains the only long-term solution for CHS, having an effective rescue medication for acute episodes could prevent the dangerous complications of prolonged vomiting—like the Wernicke's encephalopathy described in RTHC-00164.
The NK1 receptor pathway makes biological sense for CHS: substance P (which NK1 receptors mediate) is involved in the vomiting reflex, and the endocannabinoid system interacts with substance P signaling in the brainstem.
Why it matters
CHS is becoming more common as cannabis use increases, particularly among young people (RTHC-00162). Current treatment options are limited and often ineffective for severe episodes. If aprepitant proves effective in larger studies, it could become a critical rescue medication—preventing the prolonged vomiting that can lead to dehydration, electrolyte imbalances, kidney injury, and even brain damage (RTHC-00164).
The numbers in context
2 adolescent patients. 36–45 hours of failed standard treatment. Vomiting resolved within 1 hour of aprepitant. Oral fluids tolerated: 1–2 hours. Solid food tolerated: 4–8 hours. Discharged next day. No additional antiemetics needed.
How the study worked
Case report of 2 adolescents meeting Rome IV criteria for CHS with documented chronic cannabis use. Both failed standard antiemetics (ondansetron, metoclopramide, haloperidol, capsaicin) for 36–45 hours. Aprepitant administered as rescue therapy. Outcomes: time to vomiting cessation, oral fluid tolerance, solid food tolerance, and discharge timing.
Who was studied
2 adolescents with chronic cannabis use presenting symptoms of Cannabinoid Hyperemesis Syndrome.
What this study cannot tell us
Only 2 cases—far too few to establish efficacy. No blinding or control condition. The timing of symptom resolution could reflect natural episode resolution coinciding with aprepitant administration. Rome IV criteria for CHS are relatively new and may not capture all cases. No long-term follow-up on CHS recurrence. Aprepitant is an expensive medication.
How to read the evidence
Two-patient case report—promising but requires controlled trials to establish efficacy beyond anecdotal evidence.
When this study was published
Published in 2025 in the Journal of Adolescent Health, reflecting the increasing recognition of CHS in young people.
The bigger picture
This is directly relevant to RTHC-00164's case of CHS-induced Wernicke's encephalopathy after 8 weeks of vomiting. If aprepitant had been available as a rescue medication in that case, the prolonged vomiting—and resulting brain damage—might have been prevented. The growing CHS case literature (also reflected in RTHC-00162's review of increasing cannabis-related ER visits) underscores the need for better acute treatment options beyond telling patients to stop using cannabis.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Would aprepitant prove effective in a randomized trial against standard CHS treatments? Should it be used early (instead of as rescue after 36+ hours of failure) for faster resolution? Could NK1 receptor antagonists be developed specifically for CHS?
Read the original research
Cannabinoid Hyperemesis Syndrome in Adolescents: The Role of Aprepitant as a New Treatment Option for Rapid Symptom Relief.
The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 77(6), 1223-1225
The Journal of Adolescent Health is a respected publication focusing on health issues affecting adolescents.
Citation
Sigal, Anat; Padilla, Gabrielle; Carroll, Taryn; Mautone, Susan G. (2025). Cannabinoid Hyperemesis Syndrome in Adolescents: The Role of Aprepitant as a New Treatment Option for Rapid Symptom Relief.. The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 77(6), 1223-1225. https://doi.org/10.1016/j.jadohealth.2025.08.004
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