Is haloperidol better than ondansetron for treating cannabis hyperemesis syndrome?

Haloperidol was superior to ondansetron (difference 2.3 cm on VAS, 95% CI 0.6-4.0, p=0.01) with similar improvements in both pain and nausea. Haloperidol patients required fewer rescue antiemetics (31% vs 59%) and had shorter ED stays (3.1 vs 5.6 hours, difference 2.5 hours, p=0.03). Two patients in the higher-dose haloperidol group returned with acute dystonia.

Triple-blind randomized controlled trial. 33 cannabis users with active emesis randomized to haloperidol (with nested randomization to 0.05 or 0.1 mg/kg) or ondansetron 8 mg IV. Primary outcome: reduction in abdominal pain and nausea on 10-cm VAS at 2 hours.

This is one of the first RCTs comparing treatments for CHS. The superiority of haloperidol over ondansetron (a first-line antiemetic) confirms anecdotal reports and provides evidence to change emergency department practice for this increasingly common condition.

The efficacy of haloperidol (a dopamine antagonist) over ondansetron (a serotonin antagonist) provides insight into CHS pathophysiology, suggesting dopaminergic rather than serotonergic mechanisms underlie the vomiting. This has implications for understanding why traditional antiemetics fail in CHS.

Small sample (n=30 treated). Single-center study. Acute dystonia occurred with higher-dose haloperidol, raising safety concerns. Short-term outcomes only; no follow-up for recurrence.