Habboushe J, Rubin A, Liu H, Hoffman RS. The prevalence of cannabinoid hyperemesis syndrome among regular marijuana smokers in an urban public hospital [published online ahead of print January 12, 2018]. Basic Clin Pharmacol Toxicol.
To gather data on the prevalence of cannabinoid hyperemesis syndrome (CHS) in regular users of marijuana.
Prospective, observational study
Patients (aged 18 to 49 years) who presented to the emergency room department of an urban public hospital; of 2,127 patients approached for participation, 155 met the frequency criteria for marijuana use, which was smoking marijuana at least 20 days per month.
Study Parameters Assessed
A questionnaire was administered (by a trained research associate) to patients presenting at the emergency department. The survey included questions related to CHS symptoms (nausea and vomiting) and Likert scale rankings on 11 symptom-relief methods, including “hot showers.”
Primary Outcome Measures
Patients were classified as experiencing a phenomenon consistent with CHS if they reported smoking marijuana at least 20 days per month and also rated “hot showers” as 5 or more on the 10-point symptom-relief method Likert scale for nausea and vomiting.
Among those surveyed, 32.9% (95% confidence interval [CI]: 25.5%-40.3%) met the criteria for having experienced CHS.
Cannabinoid hyperemesis syndrome is a unique entity associated solely with cannabinoid use. Patients typically present with cyclical vomiting, diffuse abdominal pain, and (interestingly) relief with hot showers. Patients experiencing CHS may present to the emergency room repeatedly and undergo extensive evaluations including laboratory examination, imaging, and in some cases unnecessary procedures. They will often be treated with an array of pharmacologic interventions, including opioids, that not only lack evidence to support their use in this context but may also be harmful.1
Cecilia Sorensen is a physician in the emergency department (ED) at University of Colorado Hospital at the Anschutz medical campus who has studied the syndrome. Sorensen, in a recent interview with the New York Times, reported that the number of cases of cyclic vomiting syndrome seen in her ED doubled after marijuana was legalized in Colorado, believing that many of these cases were probably related to marijuana use.2
However, we have to keep marijuana on our differential list as a possible cause of a range of GI symptoms, including nausea, vomiting, anorexia, weight loss, and chronic pain.
In March 2017, Sorensen and colleagues published a systematic review of the literature regarding CHS.3 In their search of the medical literature, 1,253 abstracts were reviewed and 183 papers were ultimately included in their analysis. Diagnostic characteristics of CHS were identified, and the frequency of major characteristics was as follows:
- History of regular cannabis for any duration of time (100%)
- Cyclic nausea and vomiting (100%)
- Resolution of symptoms after stopping cannabis (96.8%)
- Compulsive hot baths with symptom relief (92.3%)
- Male predominance (72.9%)
- Abdominal pain (85.1%)
- Weekly cannabis use (97.4%).
Episodes of CHS typically last 24 to 48 hours but may last a week or longer. Cannabis cessation appears to be the best treatment. A September 2017 review by Khattar and Routsolias reported similar symptoms as the Sorensen review.4
Symptoms of CHS are in a way paradoxical to the long-recognized antiemetic effects of cannabinoids. Many of our cancer patients are using marijuana in the hope of reducing nausea and vomiting that are secondary to chemotherapy. In at least some cases, patients may mistakenly be attributing the symptoms of CHS to the cancer treatments they are receiving rather than to the cannabinoids they are ingesting. This may be hard to differentiate except for the peculiar symptom that CHS is relieved by heat, typically very hot showers.
There are 2 main cannabinoid receptors: CB1 and CB2. The CB1 receptors are found primarily in the central nervous system while the CB2 receptors are found primarily in the peripheral system, including the gastrointestinal (GI) tract. The cannabinoid receptors regulate and fine-tune neurotransmitter release. The severe vomiting triggered in CHS may be secondary to brainstem effects or enteric neuron effects. Chronic exposure to cannabinoids causes downregulation of the endocannabinoid receptors in animal models. Triggering the peripheral receptors in the enteric nerves may slow gastric motility.
The transient receptor potential vanilloid-1 (TRPV-1) is a G-protein coupled receptor known to interact with the endocannabinoid system. This receptor appears to play an important role in regulating body temperature,5 and is activated by heat (temperature greater than 41°C). This may explain the clinical relief of CHS symptoms by hot showers/baths.6
The TRPV-1 receptors may also explain another curious phenomenon: symptoms of CHS can be temporarily reduced by topical application of capsaicin. Capsaicin also activates TRPV-1 receptors. In January 2018 Andrew Moon and colleagues reported that topical capsaicin provided significant albeit temporary symptom relief in a patient suffering from severe CHS. They proposed that long-term use of cannabis may decreases TRPV-1 signaling and affect gastric motility.6
Moon wasn’t the first to report use of capsaicin to treat CHS. Khattar et al listed capsaicin as a possible treatment for CHS in their 2017 review,6 and in 2014 LaPoint and colleagues reported a complete resolution of nausea and vomiting in a series of 5 patients following the application of capsaicin cream to the abdomen.7 Similar responses were reported by LaPoint in a separate paper that same year.8 The only known receptor in the body that interacts with capsaicin is TRPV-1. In a 2017 paper, Dezieck et al summarized 13 case histories of patients at EDs in Massachusetts and Illinois whose symptoms were relieved with topical capsaicin.9
Guidelines published in March 2018 in the Western Journal of Emergency Medicine describe how capsaicin is used to treat CHS:
Capsaicin 0.075% can be applied to the abdomen or the backs of the arms. If the patients can identify regions of their bodies where hot water provides symptom relief, those areas should be prioritized for capsaicin application. Patients should be advised that capsaicin may be uncomfortable initially, but then should rapidly mimic the relief that they receive with hot showers.1
Thus the current theory of CHS is that chronic cannabinoid exposure inactivates the TRPV-1 receptors, which leads to nausea and vomiting due to central effects and vagal afferents. And the TRPV-1 inactivation changes gastric motility. Both heat and capsaicin applied to the skin appear to relieve symptoms; it is possible that heat and capsaicin reactivate TRPV-1 to normalize motility and at least temporarily reduce emesis.
The actions of cannabis on the digestive tract are complex. Endogenous circulating cannabinoids may have a protective effect on the GI tract and their receptors may prove to be a therapeutic target for treating some GI conditions, especially inflammatory bowel diseases. However, we have to keep marijuana on our differential list as a possible cause of a range of GI symptoms, including nausea, vomiting, anorexia, weight loss, and chronic pain.10
Given that approximately 1 in 3 regular marijuana users in this study were having symptoms of CHS, and considering the subgroup of patients who choose naturopathic care, it is possible that a significant number of our patients may be suffering from CHS but remain undiagnosed.