Systematically Testing the Evidence on Marijuana

Cannabinoid Hyperemesis Syndrome

By: Sean Reid, MD and Rachel S. Wightman, MD FACMT

Despite being commonly recognized for its antiemetic properties, cannabis has also more recently been associated with cyclic vomiting in some individuals with chronic use. Cyclic vomiting is defined as episodes of severe recurrent vomiting without a clear cause separated by periods of baseline health.¹

Cannabinoid Hyperemesis Syndrome (CHS), first described in 2004,² is characterized by cyclic vomiting that occurs in the context of chronic daily or near-daily cannabis use. Compulsive use of hot water bathing or showering to relieve symptoms has been described but is not required for diagnosis. Ultimately, cannabis abstinence is the only documented treatment to date that results in disease resolution,^3,4 though with limited longitudinal follow up data available, the required period of abstinence is poorly characterized.

Evidence Highlights

The majority of CHS research to date has been focused on characterizing the syndrome, exploring acute symptomatic treatments, and attempting to determine the prevalence of CHS cases.

Most patients with suspected CHS present to the emergency department for acute treatment of symptomatic vomiting due to dehydration and the lack of alternate outpatient options for management. These patients often respond poorly to standard antiemetic therapies such as ondansetron and metoclopramide and instead require alternative regimens that can include medications like topical capsaicin,^5-8 antipsychotics,^9-11 and benzodiazepines¹² as summarized in a 2021 systematic review by Senderovich et al. ³ Notably, this review highlights the paucity of quality data in regards to treating CHS as it describes a total of two randomized control trials and three retrospective cohort studies, with the remainder being case series and case reports.

There is significant overlap of CHS with other cyclic vomiting syndromes and it remains controversial whether CHS should be characterized as a subset of cyclic vomiting or its own entity.¹³ This, in combination with factors such as patients’ hesitancy to disclose cannabis use, has led to highly variable reports of CHS prevalence.^14-17

Clinical Considerations

Making a CHS diagnosis should only occur once more immediately concerning alternate etiologies have been ruled out.

Resolution of symptoms with cessation of cannabis use is central to the diagnosis of CHS, and a requirement of current proposed diagnostic criteria.⁴

Rome IV Diagnostic Criteria

The Rome Foundation. Rome IV Criteria. Rome Foundation. Published January 16, 2016. Accessed September 21, 2022. https://theromefoundation.org/rome-iv/rome-iv-criteria/

Based on limited evidence, it is reasonable to trial medications such as low-dose haloperidol, topical capsaicin, or benzodiazepines for symptom control early in an acute treatment setting when one has high suspicion for CHS, or after more standard modalities fail to resolve a patient’s symptoms when there is diagnostic uncertainty.

Engaging resources such as social workers, addiction specialists, and other community and behavioral supports should be considered when making recommendations for cannabis cessation to patients with chronic cannabis use and suspected CHS.

Bottom Line

• Despite the high likelihood that CHS cases will continue to rise in the setting of increased legal access to cannabis,^1,18 we don’t fully understand the root cause of CHS or why cyclic vomiting occurs in some individuals with chronic cannabis use but not others.
• Many therapies for acute symptom control have been proposed but their efficacy is still debated. Data on long term treatment options and disease phases, pathophysiology, and prevention is limited.
• Stopping cannabis use is the only documented way to resolve CHS.

Citations

1. Perisetti A. Cannabis hyperemesis syndrome: an update on the pathophysiology and management. Ann Gastroenterol. 2020;33(6). doi:10.20524/aog.2020.0528
2. Allen JH. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut. 2004;53(11):1566-1570. doi:10.1136/gut.2003.036350
3. Senderovich H, Patel P, Jimenez Lopez B, Waicus S. A Systematic Review on Cannabis Hyperemesis Syndrome and Its Management Options. Med Princ Pract. 2021;31(1):29-38. doi:10.1159/000520417
4. The Rome Foundation. Rome IV Criteria. Rome Foundation. Published January 16, 2016. Accessed September 21, 2022. https://theromefoundation.org/rome-iv/rome-iv-criteria/
5. McConachie SM, Caputo RA, Wilhelm SM, Kale-Pradhan PB. Efficacy of Capsaicin for the Treatment of Cannabinoid Hyperemesis Syndrome: A Systematic Review. Ann Pharmacother. 2019;53(11):1145-1152. doi:10.1177/1060028019852601
6. Wagner S, Hoppe J, Zuckerman M, Schwarz K, McLaughlin J. Efficacy and safety of topical capsaicin for cannabinoid hyperemesis syndrome in the emergency department. Clin Toxicol (Phila). 2019;58(6):471-475. doi:10.1080/15563650.2019.1660783
7. 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). doi:10.1111/acem.14062
8. Yusuf HM, Geier C, Staidle A, Montoy JCC. Efficacy of Topical Capsaicin for The Treatment of Cannabinoid Hyperemesis Syndrome: A Retrospective Cohort Study. Am J Emerg Med. 2021;43:142-148. doi:10.1016/j.ajem.2021.01.073
9. Witsil JC, Mycyk MB. Haloperidol, a Novel Treatment for Cannabinoid Hyperemesis Syndrome. Am J Ther. 2017;24(1):e64-e67. doi:10.1097/mjt.0000000000000157
10. Moussa G, Genest M, Villeneuve E, Wang JJ. Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial. Ann Emerg Med. 2021;77(5):555. doi:10.1016/j.annemergmed.2020.12.016
11. 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. doi:10.1080/15563650.2018.1564324
12. Kheifets M, Karniel E, Landa D, Vons SA, Meridor K, Charach G. Resolution of Cannabinoid Hyperemesis Syndrome with Benzodiazepines: A Case Series. Isr Med Assoc J. 2019;21(6):404-407.
13. Venkatesan T, Levinthal DJ, Li BUK, et al. Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome. Neurogastroenterol Motil. 2019;31(S2). doi:10.1111/nmo.13606
14. Aziz I, Palsson OS, Whitehead WE, Sperber AD, Simrén M, Törnblom H. Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults. Clin Gastroenterol and Hepatol. 2019;17(5):878-886. doi:10.1016/j.cgh.2018.05.020
15. Habboushe J, Rubin A, Liu H, Hoffman RS. The Prevalence of Cannabinoid Hyperemesis Syndrome Among Regular Marijuana Smokers in an Urban Public Hospital. Basic Clin Pharmacol & Toxicol. 2018;122(6):660-662. doi:10.1111/bcpt.12962
16. Sandhu G, Smith S, Stephenson K, et al. Prevalence of cannabinoid hyperemesis syndrome and its financial burden on the health care industry. Baylor University Medical Center Proceedings. 2021;34(6):654-657. doi:10.1080/08998280.2021.1937874
17. Kim HS, Anderson JD, Saghafi O, Heard KJ, Monte AA. Cyclic Vomiting Presentations Following Marijuana Liberalization in Colorado. Bird S, ed. Acad Emerg Med. 2015;22(6):694-699. doi:10.1111/acem.12655
18. National Conference of State Legislatures. State Medical Marijuana Laws. Ncsl.org. Published November 29, 2021. Accessed September 21, 2022. https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx

Suggested citation: Reid S, and Wightman RS. Cannabinoid Hyperemesis Syndrome. The Systematically Testing the Evidence on Marijuana Project. January 2023. https://www.cannabisevidence.org/clinician-resources/clinician-briefs/cannabinoid-hyperemesis-syndrome/

Acknowledgments: Thank you to Robert Jackman, MD and Devan Kansagara, MD MCR for critically reviewing this document. 

Author affiliations: Department of Emergency Medicine; Warren Alpert Medical School of Brown University; Providence, RI 

Grant funding: Dr. Wightman is partially supported by the National Institute of General Medical Sciences of the NIH (P20GM12550), by the National Institute on Drug Abuse of the NIH (R21DA055023; UG3DA056880), and by a Foundation for Opioid Response Efforts (FORE) award. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Health or FORE Foundation.