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The department is filled with the sound of retching as you approach the room of the next patient, a 29-year-old male with nausea, vomiting, and abdominal pain. Although the patient received ondansetron in the ambulance, he is still uncomfortable. He reveals that he has had similar episodes of generalized abdominal pain, nausea, and vomiting in the past. Taking a hot shower sometimes helps. He has not had fevers or diarrhea, and his abdominal exam is benign. Before exiting the room, you have one remaining question to ask: Does he use marijuana, and if yes, how often? 

Cannabinoid Hyperemesis Syndrome

This is a classic case of cannabinoid hyperemesis syndrome (CHS). The treatment, cessation of marijuana use, will not provide immediate relief in the emergency department. So what do you do in the meantime?

CHS, first characterized in 2004, presents similarly to other cyclic vomiting syndromes.¹ CHS is characterized by nausea, vomiting (classically described as cyclic), and abdominal pain in patients with chronic use of marijuana. Patients frequently report that hot showers relieve symptoms, and some have described compulsive bathing.² For some, CHS seems at odds with the long-touted antiemetic properties of tetrahydrocannabinol (THC). How could an antiemetic cause a cyclic vomiting syndrome? 

The mechanism underlying CHS is not entirely clear, but it is believed that the gastrointestinal effects are a result of activation of cannabinoid 1 (CB1) receptors, which inhibit gastric emptying and motility. With chronic use, THC can at times emerge from adipose tissue and enter the bloodstream, potentially contributing to a bout.

In many instances, ondansetron does not suffice in treating CHS.³ Fortunately, the butyrophenones—haloperidol and droperidol—have emerged as promising treatments.  Reports of the success of haloperidol and droperidol have largely been documented in case series and retrospective studies.⁴ These medications have a track record of efficacy in postoperative nausea and migraine headaches, so it is credible that they might be effective in CHS. Until recently, the best available evidence was a retrospective study of patients who received droperidol, most of whom received 0.625 mg or 1.25 mg. Patients who received droperidol had a shorter length of stay (6.7 hours versus 13.9 hours).⁴ However, we now have a small prospective randomized trial comparing haloperidol to ondansetron in CHS, which was published in the Annals of Emergency Medicine.

New Evidence

In this trial, Ruberto et al randomized 13 patients to intravenous haloperidol (either 0.05 or 0.1 mg/kg) and 17 patients to 8 mg of intravenous ondansetron.⁵ Haloperidol outperformed ondansetron at two hours after treatment, reducing pain and nausea 2.3 points more than ondansetron on a 0–10 scale (difference 2.3 cm; 95% CI, 0.6–4.0). The authors sliced and diced the data, looking at multiple outcomes (various pain and nausea measurements, administration of rescue medications, and length of stay). Essentially, all of the secondary outcomes favored haloperidol, although these results are not conclusive given the small size and design of the trial. 

While the study was too small to demonstrate the superiority of one dose of haloperidol over the other in a statistical manner, when the researchers looked at trends in pain scores, the high-dose haloperidol group did not seem to trend to faster or better reduction of pain and nausea. Importantly, there were three occurrences of akathisia or dystonia in patients in the haloperidol group—all of whom received the high-dose haloperidol regimen. Although the study is small, these results are conclusive enough to state the following: Forget the idiom that says, “go big or go home.” In fact, the low-dose haloperidol group was something of a misnomer; subjects in the “low-dose” group received what many of us would consider to be a normal, if not hefty, dose of haloperidol. Most subjects in the “low-dose” arm of the study received more than the 2.5 mg IV dose that many practitioners use for nausea and vomiting today. The “high-dose” group meanwhile, might have better been called the “very high-dose” group—a 70-kg patient would have received 7 mg of haloperidol. 

Turning Up the Heat

In addition to haloperidol and droperidol, capsaicin has been touted as a treatment for CHS in numerous case reports.^6-9 Similar to hot showers, this topical treatment activates receptors responsible for the sensation of heat and has been used as an analgesic. In Academic Emergency Medicine, Dean et al report results from a pilot randomized trial of 30 patients with CHS.¹⁰ In this blinded trial, 17 patients were randomized to 0.1% topical capsaicin and 13 to a moisturizing lotion placebo. At 30 minutes, nausea fell by about 2 points on a 10-point scale in both groups. But at 60 minutes, nausea was reduced by another full point in the capsaicin group, while those in the placebo group reported no change. Fewer patients in the capsaicin group received antiemetics both before randomization and as a rescue medication. 

Although these randomized studies are small, they confirm the treatment of CHS that many have adopted on the grounds of anecdotes, retrospective data, and clinical practice. It appears that the butyrophenones (haloperidol and droperidol) are effective antiemetics and capsacin may also have a role.

Dr. Westafer (@LWestafer) is assistant professor of emergency medicine and emergency medicine research fellowship director at the University of Massachusetts Medical School–Baystate, and co-host of FOAMcast.

References

1. Allen JH, de Moore GM, Heddle R, et al. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut. 2004;53(11):1566-1570.
2. Simonetto DA, Oxentenko AS, Herman ML, et al. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc. 2012;87(2):114-119.
3. Chang YH, Windish DM. Cannabinoid hyperemesis relieved by compulsive bathing. Mayo Clin Proc. 2009;84(1):76-78.
4. Lee C, Greene SL, Wong A. The utility of droperidol in the treatment of cannabinoid hyperemesis syndrome. Clin Toxicol (Phila). 2019;57(9):773-777.
5. Ruberto AJ, Sivilotti MLA, Forrester S, et al. Intravenous haloperidol versus ondansetron for cannabis hyperemesis syndrome (HaVOC): a randomized, controlled trial. Ann Emerg Med. 2020;S0196-0644(20)30666-1.
6. Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clin Toxicol (Phila). 2017;55(8):908-913.
7. Graham J, Barberio M, Wang GS. Capsaicin cream for treatment of cannabinoid hyperemesis syndrome in adolescents: a case series. Pediatrics. 2017;140:e20163795.
8. Moon AM, Buckley SA, Mark NM. Successful treatment of cannabinoid hyperemesis syndrome with topical capsaicin. ACG Case Rep J. 2018;5:e3.
9. Wagner S, Hoppe J, Zuckerman M, et al. Efficacy and safety of topical capsaicin for cannabinoid hyperemesis syndrome in the emergency department. Clin Toxicol (Phila). 2020;58(6):471-475.
10. Dean DJ, Sabagha N, Rose K, et al. A pilot trial of topical capsaicin cream for treatment of cannabinoid hyperemesis syndrome. Acad Emerg Med. 2020;27(11):1166-1172.