Cannabinoid Hyperemesis Syndrome

Aka: Cannabinoid Hyperemesis Syndrome, Cannabis Hyperemesis Syndrome, Cannabinoid Hyperemesis

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II. Pathophysiology

  1. Associated with chronic Marijuana use
  2. Proposed mechanisms
    1. Cerebral fat deposition of lipophilic Marijuana metabolites with frequent Marijuana use
    2. THC binding to vanilloid receptors in the Hypothalamus (transient receptor potential vanilloid receptor, TRPV1)
      1. Low THC concentrations and warmer Temperatures (>109.4 F or 43 C) are Anti-emetic
      2. High THC concentrations are pro-emetic

III. Diagnosis

  1. Essential criteria
    1. Chronic Marijuana use
  2. Major criteria
    1. Severe cyclical Nausea or Vomiting
    2. Abdominal Pain
    3. Weekly Marijuana use (esp. >=4 days/week for prior year)
    4. Improves with Marijuana cessation (resolves completely after 6 months of abstinence)
    5. Hot showers or baths help to relieve Nausea
  3. Supportive criteria
    1. Age under 50 years
    2. Weight loss over 5 kg
    3. Symptoms predominant in morning
    4. Normal bowel habits
    5. Negative diagnostic evaluation

IV. Management

  1. Home
    1. Marijuana cessation
    2. Symptomatic relief with hot showers or bath
    3. Capsaicin (see below)
  2. Emergency Department
    1. Antiemetics (e.g. Ondansetron, Prochlorperazine, Promethazine, Metoclopramide)
      1. Typically less effective in canabinoid hyperemesis
    2. Capsaicin cream (0.075%)
      1. May work on vanilloid receptors in Hypothalamus (similar to the action of a hot shower)
      2. Emergency Department Protocol
        1. Apply 0.075% Capsaicin cream as a thin film every 4 hours until symptoms resolve
        2. Apply cream to 15 x 25 cm or palm sized area periumbilical area using a gloved finger
        3. Peak effect in 20-30 minutes and lasts 3 hours
      3. References
        1. LoVecchio (2022) Crit Dec Emerg Med 36(6): 32
        2. Dezieck (2017) Clin Toxicol 55(8): 908-13 +PMID:28494183 [PubMed]
    3. Haloperidol
      1. Haloperidol 2.5 mg IV or IM
        1. Some studies have used doses as high as 0.05 to 1 mg/kg IV (higher than typical dosing)
        2. Jones (2016) Case Rep Psychiatry +PMID: 27597918 [PubMed]
        3. Ruberto (2021) Ann Emerg Med 77(6):613-619 +PMID:33160719 [PubMed]
    4. Inapsine (Droperidol)
      1. Dosing: 0.625 mg to 2.5 mg IV
      2. Author adds Droperidol to a bag of Normal Saline to more slowly infuse, and reduce Akathisia risk)
      3. Lee (2019) Clin Toxicol 57(9): 773-7 [PubMed]
  3. Other medications that may considered in Emergency Department refractory cases
    1. Aprepitant
      1. Parvataneni (2019) Cureus 11(6):e4825 +PMID: 31403013 [PubMed]
    2. Erector Spinae Plane Block
      1. Mechanism: Blocks afferent pain pathways
      2. Gawel (2026) Am J Emerg Med 100:93-5 +PMID: 41313935 [PubMed]
  4. Medications to AVOID
    1. Opioids
      1. Not effective in Cannabinoid Hyperemesis, and may worsen symptoms
    2. Benzodiazepines
      1. Not effective in Cannabinoid Hyperemesis, and risk for sedation, misuse and respiratory depression
      2. May consider in coingestions (esp. with stimulants)

V. Prognosis

  1. Symptoms may start to improve after first 7-10 days of Cannabis abstinence
  2. Even small amounts of Cannabis after abstinence can trigger symptoms
  3. Symptoms typically persist or recur for first 6 months of Cannabis abstinence

VI. References

  1. Orman and Zodda in Herbert (2018) EM:Rap 18(2): 10
  2. Oxentenko (2011) Mayo Internal Medicine Review
  3. Swaminathan and Rech (2026) Cannabinoid Hyperemesis, EM:Rap, 8/24/2026

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