A Pilot Trial of Topical Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome

Design

Randomized, double-blind, placebo-controlled pilot trial

N = 30

Objective

To evaluate the safety and effectiveness of the topical application of capsaicin cream as a treatment for vomiting due to suspected cannabinoid hyperemesis syndrome (CHS) in the emergency department (ED)

Study Groups

Capsaicin (n = 17)

Placebo (n = 13)

Inclusion Criteria

Adults ≥18 years; presenting with suspected exacerbation of CHS and had active vomiting or nausea in the ED

Exclusion Criteria

<18 years old; pregnant patients; allergy to capsaicin or hot peppers; resolution of nausea prior to randomization; outpatient use of prescription antiemetics within the past 24 hours (removed halfway through the trial); acute infectious or surgical abdominal conditions; did not have cyclical vomiting; had abdominal pain but no nausea; doubted cannabis use was causing symptoms

Methods

Eligible patients were randomized to receive either 5 g of topical 0.1% capsaicin cream or moisturizing cream (placebo). All patients continued to receive conventional therapy independent of study enrollment as determined by the treating physician.

Nausea was assessed using a validated visual analog scales (VAS). Researchers remained at the bedside for the first 60 minutes to assess any immediate adverse events related to the study medication. After the first 60 minutes, the patient was assessed for any additional skin-related adverse events over the entire course of the patient’s ED stay. The researchers also contacted patients after 30 days to assess for any additional skin-related adverse events and for any repeat ED or hospital visits.

Duration

Direct treatment observation: up to 1 hour

Follow-up: 30 days

Outcome Measures

Primary: severity of nausea on a visual analog scale (VAS) of 0-10 assessed at 30 minutes following medication application

Secondary: Patient-reported nausea and percent change from baseline at 60 minutes; complete relief of nausea (VAS = 0); disposition status (i.e. Admission vs Discharge); need for rescue antiemetic medication within 30 and 120 min

Baseline Characteristics

Capsaicin (n = 17)

Placebo (n = 13)

Mean Age, years

Female

Black or African American

Cannabis Use

Daily

Weekly

Less than weekly

Never

9 (52.9%)

4 (23.5%)

3 (17.5%)

1 (5.9%)

10 (75.9%)

2 (15.4%)

1 (7.7%)

0 (0.0%)

Baseline nausea VAS score

Received an antiemetic in the ED prior to randomization

Results

Capsaicin (n = 17)

Placebo (n = 13)

p-value

Nausea visual analog scale (95% CI)

After 30 min

After 60 min

% reduction from baseline at 60 min

4.1 (2.8 - 5.4)

3.2 (1.6 - 4.8)

46% (25.5% - 66.5%)

6.1 (4.1 - 8.1)

6.4 (4.7 - 8.1)

24.9% (7.8% - 41.9%)

0.075

0.007

0.120

Vomiting after study drug

Within 30 min

Within 120 min

1 (5.9%)

1 (5.9%)

4 (30.8%)

5 (38.5%)

0.138

0.061

Need for rescue antiemetic medication

Within 30 min

Within 120 min

0

3 (17.6%)

4 (30.8%)

5 (38.5%)

0.026

0.242

Hospital admission

4 (23.5%)

5 (38.5%)

0.443

Adverse Events

Common Adverse Events: None reported

Discontinued due to Adverse Events: 1 (5.9%) patient did not tolerate the treatment drug due to mild skin irritation

Study Author Conclusions

In this pilot trial, the application of topical capsaicin cream 0.1% was associated with a significant reduction in nausea at 60 minutes, but not at 30 minutes, and provided more complete relief of nausea.

InpharmD Researcher Critique

Although a pilot study, this is one of the first randomized control trials looking at capsaicin as a treatment in CHS due to prior literature being limited to case reports and retrospective studies. Strengths of this study included a double-blinded design and that there were no patients lost to follow-up once allocated to treatment arms.

Limitations include the small sample size, making this study susceptible to a type I error. A higher proportion of patients in the placebo group receiving an antiemetic medication prior to randomization, which may have added to further bias. The baseline nausea VAS was greater in the placebo group compared to those randomized to capsaicin, and the stratification of ages appeared to also be uneven.

Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents: A Case series 

Design

Case Series

Case 1

A 16-year-old female presented to the emergency room with a primary complaint of nausea, vomiting, and abdominal pain for a week. She denied fever, diarrhea, dysuria, or hematuria. She had a history of chronic cannabis use but denies using alcohol. Over the last few weeks, she increased her daily intake of cannabis as an attempt to alleviate her nausea and abdominal pain. However, the symptoms worsened. She complained of diffuse abdominal pain but had a soft abdomen without peritoneal signs.

Her vitals were normal as were her laboratory values. She received intravenous (IV) ondansetron 4 mg, metoclopramide 10 mg, a 1,000-mL normal saline bolus, and 30 mL of an oral lidocaine/diphenhydramine/aluminum/magnesium hydroxide solution. However, these were ineffective. The patient refused a computed tomographic scan and left the emergency room, despite no alleviation of her symptoms. 

Patient returned the following evening with the same complaints. Her vitals were still normal, but her pain was a 6 out of 10. Abdominal exam revealed tenderness of her left upper quadrant and epigastric region as well as a soft, nondistended abdomen. She showed no peritoneal signs. She received sublingual ondansetron 4 mg and 5 mg oral oxycodone. However, it was ineffective.

Diagnosis of exclusion and her history of cannabinoid use led to the diagnosis of cannabinoid hyperemesis syndrome (CHS). Capsaicin cream 0.025% (1-mm-thick coating) was applied to her abdomen. After thirty minutes, she reported a relief of symptoms. However, there was a mild “burning sensation” on her abdomen as a side effect of the capsaicin cream.

Case 2

A 20-year-old male also presented to the emergency rooms with the same complaint of vomiting and abdominal pain. He has a history of asthma and marijuana use for >1 year. He had significant epigastric tenderness and a soft abdomen, but no peritoneal signs. He denied having a fever, diarrhea, dysuria, or hematuria. His vital signs were normal and his abdomen was not distended but soft. He received oral fluids with ondansetron 4 mg and 15 mL of aluminum/magnesium hydroxide/diphenhydramine/lidocaine/simethicone solution by mouth. The presumed diagnose was gastritis, so he was discharged with ondansetron and ranitidine. 

The patient returned one week later with more persistent symptoms of vomiting and abdominal pains. The intensity of the pain worsened and traveled from his right lower to right upper to left upper quadrant to his epigastric region, despite using ranitidine BID and ondansetron daily. He reported hot showers alleviating his abdominal pain. An abdominal ultrasound was performed and appeared normal.

Normal laboratory exams, long-term use of cannabis, and improvement of symptoms with hot showers indicated the patient may have cannabinoid hyperemesis syndrome (CHS). Capsaicin cream 0.025% (1-mm-thick coating) was applied to his abdomen. After thirty minutes, he reported improvement of his symptoms. However, there was a mild “burning sensation” on his abdomen as a side effect of the capsaicin cream.  

Study Author Conclusions

Patients with Cannabinoid hyperemesis syndrome (CHS) may benefit from capsaicin cream 0.025% (1-mm-thick coating) to alleviate pain with one application to the abdomen, arms, and back. The only adverse effect is a mild " burning sensation" to the site of application. Patients start to notice symptom relief approximately 30 minutes after the cream is applied. 

The patient in Case 1 admitted to using marijuana in the past, while Case 2 presented with acute marijuana intoxication. Both patients benefited from capsaicin cream 0.025% (1-mm-thick coating). 

Studies have demonstrated a clinical advantage when a one-time dose of capsaicin 0.075% is applied to several adults with Cannabinoid hyperemesis syndrome (CHS). Other studies have also shown the application of capsaicin 0.075% to the abdomen and 0.025% capsaicin to the back, arms, and abdomen can be benfifical in treating Cannabinoid hyperemesis syndrome (CHS).

Successful Treatment of Cannabinoid Hyperemesis Syndrome with Topical Capsaicin

Design

Case Report

Case Presentation

A 47-year-old male with a 10-year history of daily marijuana use presented to the gastroenterology clinic with 8 years of abdominal pain, nausea, and vomiting relieved by up to 4 hours of hot-water bathing daily. Computed tomography (CT) of the abdomen and pelvis showed an unremarkable liver, no biliary duct dilatation, normal gallbladder, normal pancreatic body and head, normal spleen, and no bowel obstruction or inflammation. Other tests revealed a liver with normal size, no irregularities to the small intestine or colon, normal esophagus and gastric mucosa, and biopsies were negative for Helicobacter pylori. The patient had no improvement with dicyclomine, ranitidine, and twice-daily omeprazole. He was diagnosed with Cannabinoid Hyperemesis Syndrome (CHS) and was encouraged to discontinue marijuana.

The patient continued marijuana use and presented several weeks later to the emergency department with severe, periumbilical, stabbing pain associated with nausea and vomiting. He had a temperature of 37.1° C, heart rate 86 beats/min, blood pressure 146/74 mm Hg, and oxygen saturation 98% on ambient air. Labs showed an elevated white blood cell count 14,000 cells/µL, potassium 3.1 mEq/L, and normal hemoglobin, creatinine, blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin, lipase, and urinalysis. Abdominal CT scan showed no changes since previous scan.

He was treated with intravenous fluids, potassium, ondansetron, metoclopramide, prochlorperazine, fentanyl, viscous lidocaine, aluminum hydroxide/magnesium hydroxide/simethicone, and pantoprazole without improvement of symptoms. Capsaicin cream 0.075% was then applied to a 15×25 cm area in the periumbilical region, with reapplications every 4 hours. The patient reported burning of the skin and improvement in the intensity of his stabbing abdominal pain and nausea a few hours after the first application of capsaicin.

After the second dose, he noted complete resolution of his nausea. He received 2 more doses, which resulted in complete improvement of his abdominal pain. He was discharged the following day with a prescription for topical capsaicin. Over the following 3 months, the patient had no visits to our hospital system or any other providers included in Epic Care Everywhere within Washington State.

Study Author Conclusions

Transient receptor potential vanilloid subtype 1 (TRPV1) agonists (i.e., capsaicin) might augment TRPV1 activity and provide a less burdensome approach to treating cannabinoid hyperemesis syndrome (CHS). Additionally, topical capsaicin has a longer half-life than oral capsaicin.

Exogenous cannabinoids, including delta-9-tetrahydrocannabinol (THC), activate both CB1 and TRPV1 receptors. In vitro data suggests cannabinoids lead to dephosphorylation of TRPV1 and subsequent receptor desensitization. Chronic exposure may downregulate or desensitize TRPV1 signaling, which can lead to altered gastric motility and emesis. 

This case, as well as others, saw improvement in nausea, vomiting, and abdominal pain by the application of a topical capsaicin preparation 0.075%.

Topical Capsaicin for Treating Cannabinoid Hyperemesis Syndrome

Design

Case Report

Case Presentation

A 41-year-old female with a medical history of cannabis use, tobacco use, bipolar disorder, chronic obstructive pulmonary disease (COPD), hypertension, and reflux esophagitis, presented to the emergency department for evaluation of recurrent epigastric pain and severe nausea/vomiting. Her previous esophagogastroduodenoscopy revealed no evidence of Barrett’s esophagus or sprue; however, reflux esophagitis was detected.

For the past 2 years, she had been relatively symptom-free until recently when she began experiencing severe epigastric pain with retching and nausea. Pantoprazole was initiated and she was discharged to follow up as an outpatient. The patient returned to the emergency department a few days later with similar epigastric pain accompanied by nausea and vomiting. The patient was treated with pain medications and again with pantoprazole; then was later discharged after stabilization.

The next day, the patient returned to the emergency department complaining of severe abdominal pain, severe nausea, intermittent vomiting, and no relief from pantoprazole therapy. The patient described her pain as being worse than previous visits (rating of 10/10, twisting in nature, and some sensations of “butterflies” going up in the chest). She stated that her pain was worse when eating, and she had been unable to tolerate any solid or liquid foods. Upon physical examination, the patient had moderate tenderness to palpation in her epigastrium.

The patient was then admitted to the hospital and was given intravenous fluids, antiemetics, and one dose of morphine to decrease her pain and anxiety. The next morning, the patient’s symptoms were unchanged. A urine drug screen was ordered which came back positive for marijuana. The patient reported chronic marijuana usage, with increased use over the past 2 weeks. Concerns for cannabis hyperemesis syndrome (CHS) were raised given the episodes of abdominal pain, nausea, and vomiting with a benign abdominal exam in the setting of chronic use of marijuana.

The patient was continued on pantoprazole with the addition of metoclopramide for nausea control, but symptoms did not improve. After discussion with the patient and her spouse, a trial of capsaicin 0.1% topical cream, one application 3 times daily, was ordered with which the patient had dramatic relief and near-complete resolution of her symptoms.

Study Author Conclusions

Based on the dramatic resolution of symptoms with topical capsaicin, our case supports this promising intervention and provides an alternate approach to antiemetics and narcotics, which are routinely used in patients with cannabis hyperemesis syndrome (CHS). Topical capsaicin is available in concentrations of 0.025% 0.075%, and 0.1%, and literature suggests the higher concentrations are more effective for other conditions (e.g., neuropathic pain).