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 treatment groups (0.5mg/kg or 1mg/kg) and one ondansetron treatment group (8mg delivered intravenously over three sessions separated by seven days). Ruberto’s team used scales to rate the severity of nausea and abdominal pain before the treatment, 60 and 120 minutes after the treatment, and 24 and 48 hours after discharge from the hospital.

Ruberto found that haloperidol, at either dose, was more effective than ondansetron in providing symptomatic relief of CHS. These findings are important as they suggest that ondansetron may offer little benefit to persons with CHS. Undesirable side effects, including muscle spasms, were more common in the high-dose haloperidol group, potentially limiting its clinical utility.

A retrospective 2019 study by Carl Lee (Lee, Clin Toxicol (Phila), 2019 ) examined droperidol, an antipsychotic similar to haloperidol, and also found that it to be effective in providing symptomatic relief to persons with CHS. Lee’s study examined medical records of persons with suspected CHS. About half of patients were treated with intravenous droperidol, and about half were treated with typical antiemetics such as ondansetron. Lee found a significantly shorter hospital stay in the droperidol group than in the other antiemetic group. In addition, significantly fewer medications were needed following administration of droperidol.

Future research may benefit from comparing droperidol and haloperidol, as both are shown to have similar efficacy in reducing CHS symptoms. Comparing droperidol and haloperidol in conjunction with capsaicin cream may also be beneficial. More research is needed.

The specific cause or causes of CHS remain largely unknown, however, a recent study by Ethan Russo (Russo, Cannabis Cannabinoid Res., 2022) points to possible genetic mutations in persons with CHS that may affect cannabinoid metabolism. While ondansetron seems to be largely ineffective in the treatment of CHS, haloperidol has shown promise. Examining haloperidol’s mechanism of action may provide important clues to better understanding the causes of CHS.

People with cannabinoid hyperemesis syndrome may require hospitalization in order to maintain hydration while their nausea and vomiting persist. While anti-emetic or anti-nausea medications can treat the symptoms of CHS, the hard reality is that they aren’t solving the underlying issue. At the end of the day, the only proven way to treat CHS is to stop using marijuana. Permanent cessation of marijuana leads to the only assured cure (Richards, J Emerg Med, 2018).