Cannabinoid hyperemesis syndrome

Relation

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.

Objective

To collect data on the prevalence of cannabinoid hyperemesis syndrome (CHS) among regular marijuana users.

Draft

Prospective observational study

Participant

Patients (aged 18 to 49 years) who presented to the emergency department of an urban public hospital; Of 2,127 patients enrolled, 155 met criteria for frequency of marijuana use, i.e. h. smoking marijuana at least 20 days per month.

Study parameters assessed

A questionnaire was administered (by a trained research assistant) to patients presenting to the emergency department. The survey included questions about CHS symptoms (nausea and vomiting) and Likert scale rankings on 11 methods of symptom relief, including “hot showers.”

Primary outcome measures

Patients were classified as having 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 Likert scale for nausea and vomiting.

Key insights

Among respondents, 32.9% (95% confidence interval [CI]: 25.5%–40.3%) met criteria for CHS experience.

Practice implications

Cannabinoid hyperemesis syndrome is a unique entity that is exclusively associated with the use of cannabinoids. Patients typically present with cyclic vomiting, diffuse abdominal pain, and (interestingly) relief from hot showers. Patients with CHS may present repeatedly to the emergency department and undergo extensive evaluations, including laboratory tests, imaging, and, in some cases, unnecessary procedures. They are often treated with a range of pharmacological interventions, including opioids, which not only lack evidence to support their use in this context but may also be harmful.¹

Cecilia Sorensen is an emergency department (ED) physician at the University of Colorado Hospital at Anschutz Medical Campus who has studied the syndrome. Sorensen, in a recent interview with theNew York Timesreported that the number of cyclic vomiting cases seen in their emergency department doubled after marijuana was legalized in Colorado and believed that many of these cases were likely related to marijuana use.²

However, we must 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 literature review on CHS.³During their search of the medical literature, 1,253 abstracts were reviewed and 183 articles were ultimately included in their analysis. Diagnostic features of CHS were identified, and the frequency of key features was as follows:

• Geschichte von regelmäßigem Cannabis für einen beliebigen Zeitraum (100 %)
• Zyklische Übelkeit und Erbrechen (100 %)
• Abklingen der Symptome nach Absetzen von Cannabis (96,8 %)
• Zwanghafte heiße Bäder mit Linderung der Symptome (92,3 %)
• Männliche Dominanz (72,9 %)
• Bauchschmerzen (85,1 %)
• Wöchentlicher Cannabiskonsum (97,4 %).

Episodes of CHS typically last 24 to 48 hours but can last a week or longer. Cannabis withdrawal appears to be the best treatment. A September 2017 review by Khattar and Routsolias reported similar symptoms to Sorensen's review.⁴

The symptoms of CHS are somewhat paradoxical to the long-recognized antiemetic effects of cannabinoids. Many of our cancer patients use marijuana in hopes of reducing the nausea and vomiting that occurs after chemotherapy. At least in some cases, patients may incorrectly attribute the symptoms of CHS to the cancer treatments they are receiving rather than the cannabinoids they are taking. This can be difficult to distinguish, except for the specific symptom that CHS is relieved by heat, typically very hot showers.

There are 2 main cannabinoid receptors: CB1 and CB2. The CB1 receptors are located primarily in the central nervous system, while the CB2 receptors are primarily found in the peripheral system, including the gastrointestinal (GI) tract. The cannabinoid receptors regulate and optimize the release of neurotransmitters. The severe vomiting induced in CHS may be secondary to brainstem effects or enteric neuron effects. Chronic exposure to cannabinoids leads to downregulation of endocannabinoid receptors in animal models. Triggering the peripheral receptors in the enteric nerves can slow gastric motility.

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,⁵and is activated by heat (temperature above 41°C). This may explain the clinical relief of CHS symptoms from hot showers/baths.⁶

The TRPV-1 receptors may also explain another strange phenomenon: the 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 with severe CHS. They suggested that long-term use of cannabis may reduce TRPV-1 signaling and impair gastric motility.⁶

Moon was not the first to report the use of capsaicin to treat CHS. Khattar et al listed capsaicin as a possible treatment for CHS in their 2017 review,⁶and in 2014, LaPoint and colleagues reported a complete resolution of nausea and vomiting in a series of 5 patients after applying capsaicin cream to the abdomen.⁷Similar responses were reported by LaPoint in a separate paper the same year.⁸The only known receptor in the body that interacts with capsaicin is TRPV-1. In a 2017 publication, Dezieck et al. Compiled 13 case histories of emergency room patients in Massachusetts and Illinois whose symptoms were relieved by topical capsaicin.⁹

Guidelines published in March 2018 in theWestern Journal of Emergency Medicinedescribe how capsaicin is used to treat CHS:

Capsaicin 0.075% can be applied to the stomach or the back of the arms. If patients can identify regions of their body where hot water relieves symptoms, these areas should be prioritized for capsaicin use. Patients should be cautioned that capsaicin may initially be uncomfortable, but should then quickly mimic the relief they get from hot showers.¹

Therefore, the current theory of CHS is that chronic cannabinoid exposure inactivates TRPV-1 receptors, resulting in nausea and vomiting due to central effects and vagal afferents. And TRPV-1 inactivation alters 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 reduce vomiting, at least temporarily.

The effects of cannabis on the digestive tract are complex. Endogenous circulating cannabinoids may have a protective effect on the gastrointestinal tract, and their receptors may prove to be a therapeutic target for the treatment of some gastrointestinal diseases, particularly inflammatory bowel disease. However, we must 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 had symptoms of CHS, and considering the subset of patients who elect naturopathic treatment, it is possible that a significant number of our patients have CHS but are undiagnosed.