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Comparing Haloperidol (Haldol®), Droperidol, and Ondansetron (Zofran®) for Symptomatic Relief of Cannabinoid Hyperemesis Syndrome (CHS) in an Emergency Room Setting

Antipsychotic medications that also provide symptomatic relief of nausea and vomiting, such as haloperidol (Haldol®) or droperidol, may be more effective in providing symptomatic relief to persons with cannabinoid hyperemesis syndrome (CHS) than commonly prescribed anti-nausea medications such as ondansetron (Zofran®).

A 2020 randomized, controlled study led by Aaron Ruberto M.D. (Ruberto, Ann Emerg Med., 2020) sought to compare the effectiveness of haloperidol and ondansetron in persons with CHS. Ruberto’s 2020 study recruited long-term daily marijuana users who had experienced episodes of cyclic vomiting within the past two years. Participants were divided into two haloperidol…

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Lower doses of haloperidol were recommended (0.05 mg/kg) due to higher rates of adverse reactions with larger doses. Weight-band based dosing may be a more practical approach: Haloperidol 2.5 mg IV for adults < 80 kg, Haloperidol 5 mg IV for adults > 80 kg.

 More Than a Hot Shower – Treatment for Cannabinoid Hyperemesis Syndrome (CHS)

Previously reserved for agitated patients, haloperidol has been used off-label for postoperative nausea and has been often used successfully to treat CHS.

Articles of Interest

Cannabinoid Hyperemesis Syndrome Grand Rounds Summary

To summarize, the current evidence would best support a haloperidol-first approach to treating vomiting episodes in CHS. Since haloperidol comes in a 5 mg/ml concentration, a dose of 2.5 mg is likely reasonable for smaller patients, with a dose of 5 mg for patients larger than 80 kg. This would approximate the 0.05 mg/kg dose from the HaVOC trial. The use of capsaicin should be a shared decision with patients since there is no strong evidence to recommend it.

Drugs for Immediate Relief of Cannabinoid Hyperemesis Syndrome

It appears that the butyrophenones (haloperidol and droperidol) are effective antiemetics and capsacin may also have a role.

Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review

Multiple case reports are now finding that haloperidol has significant antiemetic effects on CHS patients in both the ED and outpatient settings.

Haloperidol as a treatment option in cannabinoid hyperemesis syndrome

Although the direct mechanism responsible for the symptoms of intractable nausea and vomiting is still unclear, haloperidol is an effective method of treatment for the hyperemetic phase of CHS and can be used as an adjunct to empiric antiemetic therapy. The most reliable treatment for CHS is complete cessation of cannabinoids.

Haloperidol vs. ondansetron for cannabis hyperemesis syndrome

In this small trial, haloperidol (0.05 or 0.1 mg/kg IV) was superior to ondansetron (8 mg IV) in the treatment of acute cannabis associated hyperemesis.

Is haloperidol the wonder drug for cannabinoid hyperemesis syndrome?

Haloperidol may be considered as an effective treatment option for patients with refractory CHS in the emergency department.

The HaVOC Trial: IV Haloperidol vs Ondansetron for Cannabis Hyperemesis Syndrome

The bottom line is that only cannabis cessation at this time appears to be the most effective treatment modality but supportive care with intravenous fluids, topical capsaicin cream, avoidance of narcotic medications, and the use of dopamine antagonists such as haloperidol (at a lower dose of 0.05mg/kg) are potentially promising adjunct modalities based on the level of evidence that we have to date.

Topical Capsaicin & Cannabinoid Hyperemesis Syndrome

Widespread availability, low cost, low adverse effect profile and ability to reduce nausea at 60 minutes are all factors that favor the use of capsaicin cream in the treatment of patients with CHS. Although not statistically significant, there were trends toward higher proportion of patients with complete nausea relief, overall rates of vomiting and need for rescue medications again favoring the capsaicin arm. Due to this study being underpowered, major conclusions cannot be drawn however this pilot trial provides direction for planning larger scale, adequately powered, clinical trials on this topic.

Treating cannabinoid hyperemesis syndrome in the emergency department

As more states legalize marijuana for recreational use, data have shown an increase in cannabis use among teenagers. Some of those teenagers may develop cannabinoid hyperemesis syndrome (CHS), a condition noted for persistent vomiting resulting from habitual cannabis use. Benzodiazepines, droperidol, haloperidol, antiemetics, acid suppression therapy, or capsaicin are all currently recommended for treatment, although no consensus exists regarding the comparative efficacy of the therapies, nor are there definitive dosing recommendations.

Trick of the Trade: Topical Treatment of Cannabinoid Hyperemesis Syndrome

Topical capsaicin cream binds to TRPV1 receptors with high specificity, impairing substance P signaling, much like a hot shower. In multiple case series and reports, capsaicin cream used in the ED was found to provide adequate relief of symptoms...

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

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.