Cannabinoid hyperemesis syndrome

CHS is a paradoxical syndrome characterized by hyperemesis (persistent vomiting), as opposed to the better known antiemetic properties of cannabinoids. The most prominent CHS symptoms are cyclical nausea, vomiting, and abdominal pain, concomitant with chronic cannabinoid use. During this phase, treatment with compulsive bathing is rarely reported, and some individuals may attempt to treat their symptoms with cannabis use. This phase can last for months to years. but in others it may take one to three months. ==Pathogenesis==

Cannabis contains more than 400 different chemicals, of which about 60 are cannabinoids. Various pathogenic mechanistic theories attempting to explain symptoms have been put forward: • dose-dependent buildup of cannabinoids and related effects of cannabinoid toxicity • the functionality of cannabinoid receptors in the brain and particularly in the hypothalamus (which regulates body temperature and the digestive system) • direct stimulation of cannabinoid receptors in the digestive system. It has been hypothesized that certain people may be genetically pre-disposed to metabolize cannabinoids in an atypical manner, making them susceptible to CHS. Another cannabinoid called cannabigerol acts as an antagonist at cannabinoid (CB1) and serotonin (5HT1A) receptors, antagonizing the anti-emetic effects of cannabidiol that occurs through its effects on serotonin. Cannabinoid buildup theory Tetrahydrocannabinol (THC) is a fat-soluble cannabinoid that can be deposited into a person's fat stores, accounting for the long elimination half-life of THC. During periods of stress or food deprivation, a person's fat stores can be mobilized (lipolysis) for energy consumption, releasing the previously stored THC back into the blood. The mechanism can be characterized as a "reintoxication effect." == Diagnosis ==

The diagnostic criteria for CHS were ill-defined prior to the establishment of the Rome IV criteria of 2016. Per the Rome IV criteria, all 3 of the following must be met to be diagnosed with CHS. They must be present for at least the last three months and the beginning of symptoms must be at least 6 months prior to the diagnosis being made. • Episodic vomiting that appears similar to cyclic vomiting syndrome • Symptom onset occurs after prolonged cannabis use • Resolution of symptoms with sustained abstinence from cannabis use Other commonly used diagnostic tests include laboratory blood tests (complete blood count, blood glucose, basic metabolic panel, pancreatic and liver enzymes), pregnancy test, urinalysis, and imaging (X-ray and CT scan). These are used to rule out other causes of abdominal pain, such as pregnancy, pancreatitis, hepatitis or infection. Differential Diagnoses Prior to diagnosing and treating for presumed CHS, more serious medical conditions need to be ruled out. The differential diagnoses include, but are not limited to, cyclic vomiting syndrome, bowel perforation or obstruction, gastroparesis, cholangitis, pancreatitis, nephrolithiasis, cholecystitis, diverticulitis, ectopic pregnancy, pelvic inflammatory disease, heart attack, acute hepatitis, adrenal insufficiency, and ruptured aortic aneurysm. However, if simple laboratory tests and imaging have excluded more serious conditions, it is reasonable to monitor for a worsening of the patient's status to prevent the unnecessary application of more invasive, and potentially dangerous, diagnostic procedures (such as exploratory surgery). In general, CHS is most often misdiagnosed as cyclic vomiting syndrome. ==Treatment==

Many traditional medications for nausea and vomiting are ineffective. Treatment is supportive and focuses on stopping cannabis use. Proper patient education includes informing patients that their symptoms are caused by their use of cannabis/cannabinoids, and that exposure to cannabinoids in the future are likely to cause their symptoms to return. If dehydration is severe, hospitalization may be required. The use of capsaicin as first-line treatment for CHS has been well tolerated, though the evidence for its effectiveness is limited. The use of antipsychotics, such as haloperidol and olanzapine, have provided partial relief of symptoms in case-reports. The evidence for the use of benzodiazepines, such as lorazepam, has shown mixed results. Other drug treatments that have been tried, with unclear efficacy, include neurokinin-1 receptor antagonists, first-generation antihistamines (e.g. diphenhydramine), 5-HT3 receptor antagonists (e.g. ondansetron), and non-antipsychotic antidopaminergics (e.g. metoclopramide). Levomepromazine may be effective for CHS but it is not available in the United States. Acetaminophen has shown some benefit in case reports for alleviating headaches associated with CHS. Opioids can provide some relief of abdominal pain, but their use is discouraged due to the risk of worsening nausea and vomiting. ==Epidemiology==

The exact proportion of the population affected by this syndrome is difficult to conclude because there have not always been specific criteria for diagnosis, there are no diagnostic tests to confirm it, and cannabis use may not be reported truthfully. Using this data, the authors estimated that roughly 2.75 million Americans suffer from CHS. An analysis of data from the National Emergency Department Sample between 2006 and 2013 found an increase in emergency room attendees with vomiting who also had cannabis use disorder, to a rate of approximately 13 per 100,000 attendees. It is possible this rise, of around times, may be affected by sampling bias, as initial awareness of CHS prompted more diligent questioning and recording of when such ER attendees were also cannabis users. The number of people affected was unclear as of 2015. CHS has been reported more frequently in people that use cannabis daily (47.9% of people with CHS) and greater than daily (23.7% of people with CHS), compared to once weekly users (19.4% of people with CHS) and less frequent users (2.4% of people with CHS). As the use of cannabis continues to be legalized at the state level, the prevalence of CHS is expected to increase in the US. A retrospective application of the 2016 Rome IV criteria to cases recorded in prior literature suggested that the number of people with CHS had been over-estimated. ==History==

Cannabinoid hyperemesis was first reported in the Adelaide Hills of South Australia in 2004 by an analysis of only 9 patients (originally 19; 10 dropped out of the study) referred to participate in this study with the goal to link cannabis to a vomiting syndrome due to the patients' previously diagnosed cyclical vomiting syndrome and that they happened to use cannabis. The name "cannabinoid hyperemesis syndrome" was also coined at this time. The report focused on nine patients who were chronic cannabis users who presented with cyclical vomiting illness. One woman in the study reported that warm baths provided the only relief from the nausea, severe vomiting, and stomach pain, and reportedly burned herself in a hot water bath three times trying to get relief. ==Society and culture==

CHS is not well known. An emergency department physician in 2018 commented that the condition wasn't on their "radar" in the five years prior, though the condition was being diagnosed more often now. Many people are surprised by the notion that cannabis can induce symptoms of nausea and vomiting, given the fact that cannabis is used to prevent nausea and vomiting. Actor David Krumholtz told The New York Times in 2024 that he had lost over 100 pounds and needed to be hospitalized several times due to cannabinoid hyperemesis syndrome. Krumholtz admitted that he'd spend up to 10 hours at a time in hot baths to relieve symptoms. After CHS nearly cost him his role in the 2023 film Oppenheimer, he quit using cannabis permanently. == References ==