All Pharmacy Pearls

Introduction

●

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

and analgesics in patients who chronically use cannabis.

o

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

●

Cannabis cessation is the only current definitive treatment of CHS.

o

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

o

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

Clinical Detail

Comparative pharmacology of agents used in CHS symptom management.

CapsaicinDopamine 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

Summary of published evidence, grouped by drug class (Capsaicin, Dopamine Antagonists, Benzodiazepines).

Author, YearDesign (Sample Size)Intervention & ComparisonOutcomes
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 capsaicinCapsaicin 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 significant reduction in nausea/vomiting at 30 and 60 minutes by visual analog scale (difference -2, 95% CI 0.2 to -4.2; difference -3.2, 95% CI -0.9 to -5.4)
Wagner et al., 2020Retrospective, matched cohort (n=43)Topical capsaicin (varying strengths) vs no capsaicinTrend 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
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 droperidolLength 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
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

●

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

Source PDF

PFP – Pharmacotherapy for cannabinoid hyperemesis syndrome.Final.pdf