The Edge: Cannabinoid Hyperemesis Syndrome and Capsaicin Cream

The Edge is a new monthly column from FlightBridgeED that will feature top providers sharing current trends in critical care and prehospital medicine. In this installment FlightBridgeED chief medical director Jeff Jarvis, MD, looks at cannabinoid hyperemesis syndrome. 

You get a call to a private residence for a 28-year-old male with abdominal pain. You are led to the living room of a well-kept home and find your patient lying in a fetal position on the couch, rocking back and forth, moaning in pain.

Seeing no hazards, you make contact with him. Your general impression is that he is uncomfortable but seems to be breathing well without tachypnea or use of accessory muscles. You’re able to feel a bounding, regular radial pulse at a rate of about 110. His skin is wet, as is his hair. 

The patient tells you he just got out of the shower. He is complaining of nausea, vomiting, and diffuse abdominal pain that he describes as cramping. He has had this off and on for the past few months. Despite multiple visits to the ED, he hasn’t received a diagnosis, and the antiemetic prescriptions he’s been given, primarily ondansetron, haven’t been helping. The only medications that seem to help with the nausea are Dilaudid and Phenergan. Although this sets off sirens in your head, he doesn’t really seem to be asking you for Dilaudid. 

There is nothing that makes this pain worse, including movement or eating. He denies any fever or diarrhea and hasn’t had any sick contacts or been tested for COVID. His senses of smell and taste are intact, and he hasn’t been coughing. The pain doesn’t radiate and comes on slowly, usually after the nausea and vomiting start. About the only thing he’s found that helps is taking hot showers. In fact, he takes multiple hot showers a day to ease the symptoms.

The only medication he takes is the prescribed ondansetron, but that isn’t helping. He has no drug allergies or other medical problems. Up until about four months ago, he was in good health. He specifically denies being a diabetic. He doesn’t drink alcohol but does smoke marijuana. He’s been smoking several joints a day for the past few years. In fact, when he first started getting these symptoms, he started smoking more because he’d heard pot helps with nausea.

Your assessment reveals the following: Vital signs are BP 118/84, HR 114, RR 20, SpO₂ 98% on room air, EtCO₂ 30, and temperature 97.8ºF, and an ECG shows sinus tachycardia without ST elevation/depression or ectopy. He is awake and alert without disorientation or apparent focal weakness/neuro deficit. His lungs are clear bilaterally. Despite complaining of diffuse abdominal pain, he doesn’t really have any tenderness with palpation. Specifically, he has no Murphy’s sign or tenderness in McBurney’s point. There is no distention, hyperactive bowel sounds, rebound, or guarding.

You start an IV and give him a liter of Ringer’s with 8 mg of IV Zofran. His heart rate drops to the high 90s, but his symptoms don’t really improve. You have a long transport time, so you give him 10 mg of metoclopramide as a 10-minute infusion, also without improvement. As you’re approaching the ED, you wonder what else might help him.

Cannabinoid Hyperemesis Syndrome

This is a classic case of cannabinoid hyperemesis syndrome (CHS). CHS is an odd idiosyncratic reaction to marijuana—odd because, as your patient correctly indicated, THC, the active ingredient in marijuana, really is an antiemetic…for most people. For some reason some folks, usually but not always with chronic daily use, actually develop uncontrolled nausea and vomiting with it. They will usually go through extensive evaluation over multiple ED visits, often with thorough GI evaluations, including unremarkable endoscopy studies, negative H. pylori tests, and normal gastric motility. 

The gastric motility part is important to differentiate this from gastroparesis, which presents similarly but is caused because of delayed transit through the GI tract. Gastroparesis is often seen in diabetics, so it is important to get this history up front. Finally, gastroparesis is not associated with marijuana use or helped by hot showers. 

The only definitive treatment for CHS is marijuana cessation. In my experience with these patients, the suggestion that marijuana might be causing their symptoms and the only way to treat the symptoms is to stop smoking it is initially met with almost universal disbelief. 

Speaking of hot showers: Along with marijuana use, taking multiple hot showers a day is almost diagnostic for CHS. While we’re not quite sure why it seems to help, there are some theories. One is that the hot showers stimulate receptors responsible for detecting heat on the skin. How does that help, you ask? No clue—but it does. The reason it is important is those receptors are also stimulated by capsaicin cream. 

Yes, that capsaicin—the burny bits from chili and pepper spray. In low concentrations it stimulates a heat sensation without pain (assuming you keep it out of your eyes, that is). So if hot showers can help these symptoms, and capsaicin cream stimulates heat perception receptors, can topical 
capsaicin cream help the CHS symptoms too? Great question. 

Capsaicin Benefit

There was a paper published last year that looked at whether topical use of this cream might help CHS symptoms.¹ This study was a pilot trial, and pilot trials are, by design, small and designed to test the feasibility of a larger study, as well as the safety and efficacy of a treatment. If something shows promise in a pilot trial, a larger study will be done that is powered to better detect differences. 

This was a small, randomized, double-blind placebo-controlled trial done in a single large urban ED. The inclusion criteria were adults over 17 with suspected CHS exacerbation of nausea and vomiting. They excluded patients who were pregnant, had an allergy to capsaicin cream or hot peppers, or had received any antiemetics in the prior 24 hours. This last exclusion had to be dropped in the middle of the trial for some interesting reasons. 

The authors found requiring patients to consent to treatment while they were symptomatic but before giving any treatment made it hard to enroll patients. Once they began enrolling patients who’d been given IV Zofran, they found more patients consented. I’m actually curious about how their IRB looked at this question initially and whether it felt there might be a danger of some patients feeling coerced into consent. I’m sure the people doing the enrolling made it clear treatment wasn’t contingent on enrollment, but I’m still curious. 

Patients were identified by the treating ER doc but consented and monitored by research associates working in the ED. These folks were available in the ED from 8 a.m. to midnight seven days a week, excluding holidays. These associates would handle the consent, enrollment, data collection and reporting, and even stay in the room with the patient for the first 60 minutes of treatment to monitor for adverse events. 

The intervention was topical administration of 5 g 0.1% capsaicin cream to the abdomen. The control was a moisturizing cream that looked similar. Neither cream had an odor. Both were administered by the ED nurse from unmarked tubes. Patients were randomized on a 1:1 basis 
stratified by sex.

The primary outcome was the amount of nausea at 30 minutes using a visual acuity scale similar to the pain scale we’re all familiar with. Secondary outcomes were nausea score at 60 minutes, side effects, and need for rescue medication.

Interestingly, just like with the pain score, there is a validated minimal clinically important reduction in nausea. Both pain and nausea scores are considered clinically important when there is a reduction of more than 2.1 on a 0–10 scale. That’s good to know. They also reported the proportion of patients in each group who had complete resolution of symptoms. 

Results

They enrolled 30 patients after screening over 600. Turns out it was hard to find these folks and get them enrolled. Seventeen patients were randomized to the intervention group, and 13 to the placebo group. That means there were 581 patients screened but not eligible. Fifty-six declined to participate, many because they couldn’t believe marijuana was causing their symptoms. 

Those who received capsaicin were older, more likely to be female, and had more nausea at baseline. Overall, despite a trend toward less nausea with capsaicin, they found no significant difference in nausea scores at 30 minutes, but they did find less nausea at 60 minutes and less need for rescue medications at 30 minutes. They also found more patients had complete resolution of symptoms with capsaicin cream (29%) than with placebo (0%). 

This was just a small pilot trial, so it isn’t worth delving too deeply into the numbers, but it looks like with a larger study there might be more clear evidence of benefit. 

So, while not definitive, these are encouraging results. It looks like the authors are interested in following this up with a larger study. 

My bottom line on this paper is that these folks are miserable, and capsaicin cream seems harmless and might help. As a bonus, it’s available over the counter. I’ll continue to use it in the ED and may even recommend sufferers give it a try at home (along with marijuana cessation).   

Reference

1. Dean DJ, Sabagha N, Rose K, et al. A Pilot Trial of Topical Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome. Acad Emerg Med, 2020 Nov; 27(11): 1,166–72.

Jeffrey L. Jarvis, MD, MS, EMT-P, FACEP, FAEMS, is chief medical director for FlightBridgeED, LLC and cohost of the FlightBridgeED EMS Lighthouse Project podcast.