Episode 558: Which is better for Cannabis Hyperemesis Syndrome – haloperidol or ondansetron?

In this episode, I’ll discuss the use of haloperidol vs ondansetron for Cannabis Hyperemesis Syndrome.

The mechanism behind Cannabis Hyperemesis Syndrome is unknown. It is a rarely occurring syndrome that seems to be associated with daily cannabis use for at least 1 year. It is a diagnosis of exclusion and is characterized by severe cycles of protracted vomiting.

Evidence to date suggests that the syndrome is resistant to traditional antiemetics and goes away eventually after cessation of cannabis use.

Due to case reports that suggested haloperidol was an effective treatment, a group of investigators in Ontario, Canada carried out a randomized controlled trial comparing haloperidol with ondansetron for Cannabis Hyperemesis Syndrome.

Cannabis users with active emesis were randomized in triple-blind fashion to 1 of three groups:

1. Haloperidol 0.05 mg/kg IV
2. Haloperidol 0.1 mg/kg IV
3. Ondansetron 8 mg IV

13 patients received haloperidol and 17 patients received ondansetron.

The primary outcome was the reduction from baseline in abdominal pain and nausea (each measured on a 10-cm visual analog scale) at 2 hours after treatment.

Both doses of haloperidol were superior to ondansetron with significant improvements in pain, nausea, reduced use of rescue antiemetics, and less time spent in the ED.

The differences favoring haloperidol were also clinically significant, with the changes from baseline more than double ondansetron’s, half the need for rescue antiemetics, and one-third shorter ED stay, saving 2.5 hours of time in the ED.

Two patients in the high dose haloperidol group did return to the ED for acute dystonia.

This trial had difficulties with enrollment and was halted early for benefit. Stopping a trial early for benefit may overstate the treatment effect, as discussed in episode 456.

However it represents the best available information on treatment of this rare syndrome. If haloperidol is used, the lower dose of 0.05 mg/kg IV makes the most sense as it was effective without causing dystonia in this small sample of patients.

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