Topical capsaicin for cannabinoid hyperemesis syndrome

Inexpensive, safe and highly effective

Introduction:

Emergency physicians are increasingly confronted with cases of cannabinoid hyperemesis syndrome (CHS). It is a challenging syndrome to manage, comprised of chronic cannabis abuse and cyclic and/or intractable episodes of nausea, vomiting and abdominal pain.[^1,2] Recurrent presentations to the ED are common and the diagnosis is frequently missed if a history of cannabis use is not explored. Traditional pharmacotherapies for nausea and vomiting including intravenous rehydration, antihistamines, serotonin antagonists like ondansetron, dopamine antagonists and benzodiazepines are typically ineffective.

Antipsychotics including haloperidol and olanzapine have shown some efficacy in limited studies.[^3,4] Unfortunately, many ED visits for CHS result in admission to observation or inpatient units, where symptoms often attenuate slowly upon cannabis cessation. Oddly, CHS patients typically report the greatest (temporary) symptom relief with hot water bathing or showering, which would be an inconvenient treatment modality in most EDs.[^5] The challenge for the ED physician is to rapidly de-escalate symptoms, avoid unnecessary diagnostic testing or admission and counsel the patient regarding cannabinoid cessation. As more and more states legalize marijuana use, we may start to see and treat more patients with CHS. Here we review topical capsaicin, a safe, inexpensive and non-invasive treatment that has shown promise in rapidly alleviating CHS symptoms.

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Notable history:

Capsaicin is a naturally-occurring component of several species of chili peppers belonging to the genus Capsicum. It is widely used in food spices and seasonings as well as pepper sprays, pest repellents, as well as topical and systemic pharmaceuticals.

In pure form, it is a potent irritant to skin and tissues, producing a hot, burning sensation on contact. It has long been used pharmacologically as a topical OTC analgesic to treat pain from arthritis, minor aches and strains, and peripheral neuralgia. Several clinical trials are ongoing to assess the efficacy of capsaicin in various neuropathies, pain, angina and CHS.

In the news:

Cannabis has long been the most prevalent illicit drug in the United States.  Recreational use is now legal in nine states. Recent epidemiologic data suggests that use is increasing nationwide. Concern over the potential for increased ED visits for CHS has stoked interest in enhancing awareness of CHS and identifying simple methods of treatment for these individuals. At this point, the efficacy of topical capsaicin is supported by small case reports and case series, describing rapid and successful treatment of nausea, cyclic vomiting and abdominal pain in ED patients with a history of significant cannabis abuse after traditional therapies failed.[^8,9,10,11]  All case reports and case series to date have included a short period of observation in the ED, with no information regarding duration of effect, need for readministration, re-presentation to the ED or clinical course after discharge.

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How it works:

The pathophysiology of CHS is not fully understood. Tetrahydrocannabinol (THC) is the primary psychoactive component in cannabis, and it is known to act on multiple receptors in the body, including the cannabinoid receptors CB1 and CB2 and the transient receptor potential vanilloid subtype 1 (TRPV1).

Historical models have placed responsibility for CHS predominantly on the cannabinoid receptors, but more recent models favor an enhanced role of TRPV1.⁶ TRPV1 is a peripheral nervous system nociceptor expressed in multiple organ systems, including the area postrema or chemoreceptor trigger zone in the brain, enteric nerves, gastric epithelium and skin. It is noted to have activity in both pain relief and body heat regulation. TRPV1 is activated by cannabinoids, nociceptive heat stimuli (i.e. hot baths) and capsaicin. Chronic use of cannabinoids is thought to downregulate TRPV1 signaling, leading to altered gastric motility, nausea and vomiting.[^7] Topical capsaicin produces a strong heat sensation upon contact with the skin acting as a potent TRPV1 agonist, alleviating the gastrointestinal symptom complex associated with CHS.

Dosing and administration:

Regimens typically include application of 0.025% to 0.075% capsaicin cream to a clean, dry area of the abdomen as a 1-mm-thick coating. Additional application of capsaicin cream to the back and arms has also been described in case reports. Onset of effect is rapid, within 5- to 10-minutes, but duration of effect and recommendations regarding repeat application remain unclear. Gloves should be worn while applying the cream, to prevent skin irritation to the provider. Patients should be cautioned not to touch their skin and particularly to avoid ocular or mucosal contact. Use in adolescent patients is described as safe and effective.[^12]

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Adverse Events:

The most commonly reported adverse reaction with topical capsaicin is a burning sensation to the skin. The potential for dermatologic reactions to a topical cream exist, but systemic side effects of topical capsaicin are unlikely. Application to the face, eyes, mouth, or areas of broken, wounded or irritated skin should be avoided.  If excessive skin irritation occurs to either the patient or provider, wash the area with cold milk to quickly relieve symptoms. Milk serves as a detergent to remove the capsaicin.

Cost:

A 1.5-3 oz. tube of capsaicin cream costs $5 to $10. If capsaicin is unavailable at your institution, it is widely available OTC in all pharmacies and drug stores nationwide for minimal cost. If institutional policy allows, it can be obtained OTC for use in the ED setting. It is reasonable and safe to consider recommendation of outpatient home application of capsaicin for patients with recurrent CHS episodes.

References

1. Allen J, de M, Heddle R, Twartz J. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut. 2004;53(11):1566-1570.
2. Sontineni SP, Chaudhary S, Sontineni V, et al. Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse. World J Gastroenterol. 2009;15(10):1264-6.
3. Richards J, Gordon B, Danielson A, Moulin A. Pharmacologic Treatment of Cannabinoid Hyperemesis Syndrome: A Systematic Review. Pharmacotherapy. 2017;37(6):725-734.
4. Lapoint J, Meyer S, Yu CK, et al. Cannabinoid Hyperemesis Syndrome: Public Health Implications and a Novel Model Treatment Guideline. West J Emerg Med. 2018 Mar;19(2):380-386.
5. Simonetto D, Oxentenko A, Herman M, Szostek J. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc. 2012;87(2):114-119.
6. Richards JR, Lapoint JM, Burillo-Putze G. Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment. Clin Toxicol (Phila). 2017;1:1-10.
7. Rudd JA, Nalivaiko E, Matsuki N, et al. The involvement of TRPV1 in emesis and anti-emesis. Temperature (Austin). 2015;2(2):258-76.
8. Khattar N, Routsolias J. Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review. Am J Ther. September 2017.
9. Lapoint J. Case series of patients treated for cannabinoid hyperemesis syndrome with capsaicin cream. Clin Tox. 2014;52:707.
10. Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clin Toxicol (Phila). 2017;55(8):908-913.
11. Román F, Llorens P, Burillo-Putze G. [Topical capsaicin cream in the treatment for cannabinoid hyperemesis syndrome]. Med Clin (Barc). 2016;147(11):517-518.
12. Graham J,  Barberio  M,  Wang  Capsaicin  cream  for  treatment  of  cannabinoid  hyperemesis  syndrome  in  adolescents:  a  case  series. Pediatrics. 2017;140(6):e20163795.