Introduction: One of the most common adverse effects of habitual cannabis use is hyperemesis—recurrent bouts of protracted vomiting, retching and abdominal pain superimposed on a baseline of daily nausea and anorexia. Largely anecdotal evidence supports the use of haloperidol, benzodiazepines or topical capsaicin over traditional antiemetics, yet little is known about the cause or optimal treatment of this newly recognized disorder. We report the results of one of the first clinical trials on so-called cannabis hyperemesis syndrome (NCT03056482). Methods: We approached adults with a working diagnosis of hyperemesis due to cannabis, provided they had ongoing emesis for >2 hours, a cyclic pattern of 3+ episodes in the last 2 years, and near daily use of cannabis by inhalation. We excluded those who were pregnant, deemed unreliable, or using opioids. Subjects provided written consent to be randomized during the index or any subsequent visit to either haloperidol (with a nested randomization to either 0.05 mg/kg or 0.1 mg/kg) or ondansetron 8 mg intravenously in a quadruple-blind fashion, and to be followed for 7 days. The primary outcome was the average reduction from baseline in abdominal pain and nausea (each measured on a 10-cm VAS) at 2 hours. While the original trial design allowed for crossover, the primary analysis used only the first treatment period since fewer than the prespecified threshold of 20% of subjects crossed over. Results: We enrolled 33 subjects, of whom 30 (16 men, 29+/-11 years old, using 1.5+/-0.9 g/day since age 19+/-2 years) were treated at least once (haloperidol 13, ondansetron 17). Haloperidol at either dose was superior to ondansetron (difference 2.3 cm [95%CI 0.6, 4.0]; p = 0.01), with similar improvements in both pain and nausea, as well as less rescue antiemetics (27% vs 61%; p = 0.04), and shorter time to ED departure (3.1+/-1.7 vs 5.6+/-4.5 hours; p = 0.03 Wilcoxon rank sum). There were two (haloperidol) vs six (ondansetron) return visits for ongoing nausea/vomiting, as well as two return visits for acute dystonia, both in the higher dose haloperidol group. Conclusion: Haloperidol is superior to ondansetron for the acute symptomatic treatment of patients with ongoing hyperemesis attributed to habitual cannabis use. The efficacy of this agent over ondansetron provides insight into the mechanism of this new disorder, now almost a daily diagnosis in many Canadian emergency departments.

Introduction: Cannabis hyperemesis syndrome (CHS) is associated with long-term, regular use of marijuana. CHS patients typically present to emergency departments (ED) during a hyper-emetic phase of paroxysmal nausea and vomiting. Despite extensive investigations as well as frequent ED presentations, CHS patients have a delayed time to diagnosis, and many are often missed. To date, there is a paucity of research examining CHS in emergency departments. Our objective was to identify CHS cases presenting to EDs within the Calgary health region, and to quantify the number of patients and frequency of ED visits for CHS. Methods: A retrospective chart review was performed on all patients who presented to any Calgary ED or urgent care center between January 1, 2015 and December 31, 2016 (ages 18 55 years) who had an ED discharge diagnosis of either nausea or vomiting alone, nausea with vomiting, or poisoning by cannabis, as identified in administrative data. Data abstraction from medical records was performed by trained personnel using standardized forms with comprehensive inclusion criteria for CHS. Results: The search strategy yielded a total of 320 ED visits from 156 individual patients. 55% of visits were by males, and 45% by females. The average age was 29.5 years. Of the 156 patients, 53% had cannabis use documented in the chart, with 51% reporting daily and/or regular cannabis use. Relief of symptoms from use of hot showers (a pathognomonic finding) was found in 17% of patients. 18% of patients (n=28) met criteria for CHS, and 28% (n=44) met partial criteria for CHS (having documented regular cannabis use, cyclic vomiting and abdominal pain) but no record of symptom resolution with cessation of cannabis use or from the use of hot showers. Patients meeting CHS criteria had an average of five repeat ED visits during the study period with 16% (n=12) of ED visits resulting in hospital admission. Conclusion: We identified a large cohort of patients with confirmed or suspected CHS. Given that nearly one third of the sample met partial criteria for CHS highlights the need for improved patient screening, as it is possible that this cohort may include missed cases. Further, many CHS patients are not responsive to first-line anti-emetics and accurate diagnosis is crucial for managing these patients effectively in the ED. This is of particular importance given the admission rate for CHS and resulting burden on the health system.