Introduction

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CHS is a syndrome of cyclic vomiting, nausea, and abdominal pain often refractory to available antiemetics

and analgesics in patients who chronically use cannabis.

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Hallmark symptom of CHS is compulsive hot bathing as it results in symptom relief.

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Cannabis cessation is the only current definitive treatment of CHS.

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Treatment is unknown, but regimens include capsaicin, dopamine antagonists, and benzodiazepines.

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Opioids should be avoided as they may exacerbate nausea and vomiting.

Clinical Detail

ParameterCapsaicinDopamine AntagonistsBenzodiazepines
Mechanism of ActionStimulates transient receptor potential vanilloid-1 (TRPV1), a G-protein coupled receptor on peripheral tissue; TRPV1 interacts with the endocannabinoid system resulting in symptom reliefAntagonizes dopamine receptor upregulation in chronic cannabis use; targets D2 receptors in the gastrointestinal tract and chemoreceptor trigger zoneStimulation of inhibitory neurotransmitter GABA to reduce nausea/vomiting anticipation; decreases activation of cannabinoid type receptor 1 (CB1) in frontal cortex
Dose2-3 inch stripHaloperidol: 1-5 mg
Droperidol: 0.625-2.5 mg		Clonazepam: 0.5 mg
AdministrationTopical application to abdomen or back of armsIV, POIV, PO, ODT
Recommended Dosage FormCream: 0.05%, 0.075%, 0.1%IVIV, ODT
Adverse EffectsBurning & itchingExtrapyramidal reactionsDrowsiness, confusion, respiratory depression
Drug Interactions & WarningsAvoid touching eyes, mouth & genitals after application; should be applied wearing gloves
*8% patch utilization may result in severe skin irritation/burns		Caution use in psychiatric disorders; QT prolonging agentCaution in hepatic and/or renal dysfunction

Evidence

Author, YearDesign (Sample Size)Intervention & ComparisonOutcomes
Capsaicin
Kum et al., 2021Retrospective, cohort (n=201)Topical capsaicin
Adult & pediatric patients		• Greater proportion of patients who received capsaicin achieved primary efficacy outcome (55 vs 21%, p<0.001, OR 1.44 [95% CI 0.586-0.820])
• Reduction in time to discharge following capsaicin admin (3.72 vs 6.11 hr, p=0.001)
Yusuf et al., 2021Retrospective, observational (n=55)Topical capsaicin vs no capsaicin• Capsaicin administration within first two rounds of medication treatment had significantly shorter length of stay (4.83 vs 7.09 h, p=0.01)
• No difference in 24 h bounceback or admission rate between groups (0.11 vs 0.10, p=0.43; 0.19 vs 0.05, p=0.07)
Dean et al., 2020Double-blind, randomized, placebo-controlled (n=30)Topical capsaicin 0.1% vs placeboCapsaicin administration was associated with a non-significant reduction in nausea/vomiting at 30 minutes (difference -2, 95% CI 0.2 to -4.2) and a significant reduction at 60 minutes (difference -3.2, 95% CI -0.9 to -5.4) by visual analog scale
Wagner et al., 2020Retrospective, matched cohort (n=43)Topical capsaicin (varying strengths) vs no capsaicin• Trend towards reduction in ED length of stay with capsaicin use (179 vs 201 min; p=0.33)
• 67% of patients did not require any additional rescue medications prior to discharge
Graham et al., 2018Case series (n=2)Topical capsaicin 0.025%
Adolescent patients		Following failure of other medications, both patients reported symptom relief within 30 minutes following capsaicin administration
Dezieck et al., 2017Multicenter case series (n=13)Topical capsaicin (varying strengths)All patients reported symptom relief following capsaicin administration though several required additional rescue medications
Dopamine Antagonists
Ruberto et al., 2021Randomized, Controlled (n=33)Haloperidol 0.05 mg/kg IV
Haloperidol 0.1 mg/kg IV
Ondansetron 8 mg IV		• Haloperidol at either dose was superior to ondansetron (diff 2.3 on VAS, 95% CI 0.6-4)
• Less use of rescue antiemetics in haloperidol group (31 vs 59%, 95% CI -61 to 13)
Lee et al., 2019Retrospective, comparative (n=76)Droperidol IV (avg dose 0.625 mg) vs no droperidol• Length of stay was significantly lower in the droperidol group (6.7 vs 13.9 hours, p=0.014)
• Ondansetron/metoclopramide use was reduced by half with the use of droperidol
Witsil et al., 2017Case series (n=4)Haloperidol 5 mg IVAll 4 patients reported resolution of nausea/vomiting within 1-2 hours of haloperidol administration
Inayat et al., 2016Case report (n=1)Haloperidol 1-2 mg IVGI symptoms and compulsive hot bathing resolved with haloperidol 1 mg; subsequent symptoms resolved with haloperidol 2 mg
Hickey et al., 2013Case report (n=1)Haloperidol 5 mg IVAll CHS symptoms completely resolved within 1 hour of haloperidol administration
Benzodiazepines
Kheifets et al., 2019Case series (n=4)Clonazepam 0.5 mg PO q8h2 patients had symptom relief after 1 dose, the remaining patients had symptom relief after 24 hours

Conclusions

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Capsaicin and dopamine antagonists appear as potential treatment options for CHS symptom management;

however the only true treatment is cannabis cessation.

References

  • Lapoint J, et al. West J Emerg Med. 2018:19(2):380-86.
  • Sorensen CJ, et al. J Med Toxicol. 2017;13:71-87.
  • Kum, et al. Am J Emerg Med. 2021;49:343-51.
  • Yusuf, et al. Am J Emerg Med. 2021;43:142-8.
  • Dean, et al. Acad Emerg Med. 2020;27(11):1166-72.
  • Wagner S, et al. Clin Toxciol (Phila). 2020;58(6):471-5.
  • Graham, et al. Pediatrics. 2017;140(6):e20163795.
  • Dezieck L, et al. Clin Toxicol (Phila). 2017;55(8):908-13.
  • Ruberto A, et al. Ann Emerg Med. 2021;77(6):613-9.
  • Lee, et al. Clin Toxicol (Phila). 2019;57(9):773-7.
  • Witsil JC, et al. Am J Ther. 2017;24(1):e64-7.
  • Inayat F, et al. BMJ Case Rep. 2017;bcr2016218239.
  • Hickey JL, et al. Am J Emerg Med. 2013;31(6):1003.e5-6.
  • Kheifets M, et al. IMAJ. 2019;21:404-7.
Tags:cannabinoid hyperemesis capsaicin haloperidol nausea