Cannabinoid hyperemesis syndrome

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Cannabinoid hyperemesis syndrome (CHS)
Specialty Gastroenterology
Symptoms Nausea, vomiting, stomach pain [1]
Complications Kidney failure
CausesLong term, heavy use of cannabis [1]
Diagnostic method Based on the symptoms [2]
Differential diagnosis Cyclical vomiting syndrome [3]
Treatment Cannabis cessation, hot baths and showers [2]
Medication Capsaicin cream [2]

Cannabinoid hyperemesis syndrome (CHS) is recurrent nausea, vomiting, and cramping abdominal pain that can occur due to prolonged, high-dose cannabis use. [4] [5] These symptoms may be relieved temporarily by taking a hot shower or bath. Complications are related to persistent vomiting and dehydration which may lead to kidney failure and electrolyte problems. [2]

Contents

Weekly cannabis use is generally required for the syndrome to occur; synthetic cannabinoids can also cause CHS. [6] [5] The underlying mechanism is unclear, with several possibilities proposed. [2] [5] Diagnosis is based on the symptoms, as well as the history of cannabis use (including a urine screen test if necessary). [6] The condition is typically present for some time before the diagnosis is made. [6]

The only known curative treatment for CHS is to stop using cannabis. [7] [2] Two weeks (or possibly up to 3 months) may be required to see a benefit. [6] [8] Treatments during an episode of vomiting are generally supportive in nature (e.g., hydration). There is tentative evidence for the use of capsaicin cream on the abdomen during an acute episode. [2]

Another condition that presents similarly is cyclic vomiting syndrome (CVS). [3] The primary differentiation between CHS and CVS is that cessation of cannabis use only resolves CHS. CVS does not resolve with the cessation of cannabis use. [5] Another key difference is that CVS symptoms typically begin during the early morning; predominant morning symptoms are not characteristic of CHS. [9] [10] Distinguishing the two can be difficult since many people with CVS use cannabis, possibly to relieve their symptoms. [5]

The syndrome was first described in 2004, and simplified diagnostic criteria were published in 2009. [11] [12]

Signs and symptoms

The long-term and short-term effects of cannabis use are associated with behavioral effects leading to a wide variety of effects on the body systems and physiological states. [12] CHS is a paradoxical syndrome characterized by hyperemesis (persistent vomiting), as opposed to the better known antiemetic properties of cannabinoids. [13] Specifically, CHS takes the pattern of cyclical nausea, vomiting, and abdominal pain in the setting of chronic cannabinoid use. [13] The abdominal pain tends to be mild and diffuse. [3] There are three phases of CHS: the prodromal phase, the hyperemetic phase, and the recovery phase. [8]

Prodromal phase

The prodromal phase is characterized by mild symptoms of CHS, including nausea, anxiety and fear related to vomiting, mild abdominal discomfort, sweating, and increased thirst; symptoms can be more severe in the morning, but this is not always the case. [14] 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. [8] [5]

Hyperemetic phase

The hyperemetic phase is characterized by the full syndromal symptoms of CHS, including persistent nausea, vomiting, abdominal pain, and retching. [8] Retching can occur up to five times per hour. Acute episodes of cannabinoid hyperemesis typically last for 24–48 hours. [3] The symptoms experienced in this phase are cyclical, and can recur unpredictably in intervals of weeks to months. [15] It is very difficult to take food or medicine by mouth during this stage, and patients may develop a fear of eating. Weight loss and dehydration due to decreased oral intake and vomiting are possible. It is during this hyperemetic phase that people with CHS are likely to present to the emergency department of the hospital for treatment. [8]

Treatment via hot water, sometimes for hours at a time, relieves symptoms for many patients, which can result in compulsive bathing or showering. People have described the hot water relief as "temperature-dependent," meaning that hotter temperatures provide greater relief. [8] [3]

Recovery phase

The recovery phase begins after the patient abstains from cannabis consumption, but the time for resolution of symptoms is unclear: it has been reported to occur within two weeks, [6] or to take one to three months. [8] Lost weight can be regained due to a restoration of normal oral intake, and compulsive bathing/showering can give way to normal patterns of behavior. [8] If a person in this phase consumes cannabis again, their symptoms tend to come back. [15] Relapses are common due to reinitiation of cannabis consumption, following which many people use or increase their use of cannabis due to concerns about nausea. Increased patient education may be necessary. [3]

Complications

Two deaths were reported due to kidney failure and electrolyte disorders secondary to dehydration from persistent vomiting. [2] [16]

Pathogenesis

Cannabis contains more than 400 different chemicals, of which about 60 are cannabinoids. [13] The chemical composition of cannabis may vary between cannabis products, making it difficult to identify the specific chemical(s) responsible for the syndrome. [17] The pathophysiology of CHS is complicated by the complex action of these chemicals throughout the body, both in the central nervous system and in the gastrointestinal system. [13] Cannabis-related factors, such as the amount of THC in the cannabis, the amount of use, and the duration of use likely play a role, but are not yet well understood. [17] Other factors, such as chronic stress, genetics, and emotional factors, may influence the risk for CHS. [17]

Various pathogenic mechanistic theories attempting to explain symptoms have been put forward: [15]

It has been hypothesized that certain people may be genetically pre-disposed to metabolize cannabinoids in an atypical manner, making them susceptible to CHS. [18] [19]

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. [3]

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. [3] 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. [3] The mechanism can be characterized as a "reintoxication effect." [3]

Diagnosis

The diagnostic criteria for CHS were ill-defined prior to the establishment of the Rome IV criteria of 2016. [20] [21] 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.

  1. Episodic vomiting that appears similar to cyclic vomiting syndrome
  2. Symptom onset occurs after prolonged cannabis use
  3. Resolution of symptoms with sustained abstinence from cannabis use [20] [21]

A complete history of the person's use of cannabinoids is important in establishing the correct diagnosis. [4] CHS has often been undiagnosed, sometimes for years. [13] This may be due to reluctance on behalf of patients to fully disclose their use of cannabis to healthcare professionals, especially when another person is accompanying the patient to an appointment or emergency department visit. [13] Identifying the correct diagnosis saves money for the healthcare system and reduces morbidity associated with the condition. [3]

A urine drug screen can be useful for objectively determining the presence of cannabinoids in a person's system. [8] Cannabinoid metabolites (specifically 11-nor-Δ9-carboxylic acid) can be detected in urine for about 2 to 8 days with short-term use, and for 14–42 days of chronic use. [22]

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). [3] 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 a presumed CHS, more serious medical conditions need to be ruled out. [4] The differential diagnoses include, but are not limited to, cyclic vomiting syndrome, [3] 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. [4] [8] 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 (e.g., exploratory surgery). [4] In general, CHS is most often misdiagnosed as cyclic vomiting syndrome. [3]

Treatment

Many traditional medications for nausea and vomiting are ineffective. [23] Treatment is otherwise supportive and focuses on stopping cannabis use. [24] Proper patient education includes informing patients that their symptoms are due to their use of cannabis/cannabinoids, and that exposure to cannabinoids in the future are likely to cause their symptoms to return. [25] Clinical pharmacists can play a role in administering this education, as well as encouraging patients to seek the assistance of mental health providers. [8] Abstinence from cannabinoids currently remains the only definitive treatment. [4] Cognitive behavioral therapy and motivational enhancement therapy are evidence-based outpatient treatment options for patients with cannabis use disorder. [3]

Symptomatic relief is noted with exposure to hot water (greater than 41°C, 106°F), which is mediated by TRPV–the capsaicin receptor. [25] Assessing for dehydration due to vomiting and hot showers is important as it can lead to acute kidney failure, and this is easily treated with IV fluids.[ citation needed ] If dehydration is severe, hospitalization may be required. [3] Based on the mechanism of the effect, some clinicians have used topical capsaicin cream applied to the periumbilical area in the treatment of acute CHS. [25] The use of capsaicin as first-line treatment for CHS has been well tolerated, though the evidence for efficacy is limited. [25] The use of hot water showers in the emergency department setting has been advocated in situations where topical capsaicin cream is unavailable, though the same precautions to hot water use (dehydration, burn injury) are required. [25] While the relationship between CHS and relief with hot water is widely documented, it is not the experience of all individuals with this condition. [26]

The use of antipsychotics, such as haloperidol and olanzapine, have provided partial relief of symptoms in case-reports. [25] [27] The evidence for the use of benzodiazepines, such as lorazepam, [27] has shown mixed results. [25] Other drug treatments that have been tried, with unclear efficacy, include neurokinin-1 receptor antagonists, [3] first-generation antihistamines (e.g. diphenhydramine), 5-HT3 receptor antagonists (e.g. ondansetron), and non-antipsychotic antidopaminergics (e.g. metoclopramide). [25]

Acetaminophen has shown some benefit in case reports for alleviating headaches associated with CHS. [8] Opioids can provide some relief of abdominal pain, but their use is discouraged due to the risk of worsening nausea and vomiting. [3]

Epidemiology

The exact proportion of the population affected by this syndrome is difficult to conclude because there has not always been a specific criteria for diagnosis, there are no diagnostic tests to confirm it, and cannabis use may not be reported truthfully. [21] A 2015 study that surveyed patients from an urban emergency department found that 32.9% of people who reported cannabis use of at least 20 days per month met criteria for CHS. [28] Using this data, the authors estimated that roughly 2.75 million Americans suffer from CHS. [28] However, the author and other experts on the subject acknowledge that there are limitations to this estimation and the prevalence of this disease can not be concluded at this time. [21] [28]

In the United States, 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 5+1⁄2 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. [29]

The number of people affected was unclear as of 2015. [30] 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). [4] A significant increase in the incidence of CHS (and other cannabis-related visits to the emergency department) has been noted in U.S. states that have legalized cannabis, with the incidence of cyclic vomiting prominently doubling in the US state of Colorado after legalization. [25] As the use of cannabis continues to be legalized at the state level, the prevalence of CHS is expected to increase in the US. [4]

As of 2017 a French pharmacovigilance program for drug users had received reports of 29 cases of CHS. At the time there were 113 case described in the international medical literature. CHS incidence is likely to have been substantially under-reported. [31] 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. [29]

History

Cannabinoid hyperemesis was first reported in the Adelaide Hills of South Australia in 2004 by an analysis of only 9 patients (originally 19 but 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 already diagnosed cyclical vomiting syndrome and that they happened to use Cannabis. [11] CHS wasn't reported in users of synthetic cannabinoids until 2013 despite widespread use occurring as early as 2009 and having a significantly higher cannabinoid receptor action than THC. [32]

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. [33]

Society and culture

CHS is not very well known. [34] 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. [35] 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. [35]

The portmanteau "scromiting" (scream + vomiting) has been used as a colloquial name for the condition, though it is not clear how widespread the use of the term is. [36] [37]

Related Research Articles

An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may be used for severe cases of gastroenteritis, especially if the patient is dehydrated.

<span class="mw-page-title-main">Effects of cannabis</span>

The effects of cannabis are caused by chemical compounds in the cannabis plant, including 113 different cannabinoids such as tetrahydrocannabinol (THC) and 120 terpenes, which allow its drug to have various psychological and physiological effects on the human body. Different plants of the genus Cannabis contain different and often unpredictable concentrations of THC and other cannabinoids and hundreds of other molecules that have a pharmacological effect, so the final net effect cannot reliably be foreseen.

<span class="mw-page-title-main">Medical cannabis</span> Marijuana used medicinally

Medical cannabis, or medical marijuana (MMJ), is cannabis and cannabinoids that are prescribed by physicians for their patients. The use of cannabis as medicine has not been rigorously tested due to production and governmental restrictions, resulting in limited clinical research to define the safety and efficacy of using cannabis to treat diseases.

Morning sickness, also called nausea and vomiting of pregnancy (NVP), is a symptom of pregnancy that involves nausea or vomiting. Despite the name, nausea or vomiting can occur at any time during the day. Typically the symptoms occur between the 4th and 16th week of pregnancy. About 10% of women still have symptoms after the 20th week of pregnancy. A severe form of the condition is known as hyperemesis gravidarum and results in weight loss.

Functional gastrointestinal disorders (FGID), also known as disorders of gut–brain interaction, include a number of separate idiopathic disorders which affect different parts of the gastrointestinal tract and involve visceral hypersensitivity and motility disturbances.

<span class="mw-page-title-main">Ondansetron</span> Medication to prevent nausea and vomiting

Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, migraines or surgery. It is also effective for treating gastroenteritis. It can be given orally, intramuscularly, or intravenously.

Cyclic vomiting syndrome (CVS) is a chronic functional condition of unknown pathogenesis. CVS is characterized as recurring episodes lasting a single day to multiple weeks. Each episode is divided into four phases: inter-episodic, prodrome, vomiting, and recovery. Inter-episodic phase, is characterized as no discernible symptoms, normal everyday activities can occur, and this phase typically lasts one week to one month. The prodrome phase is known as the pre-emetic phase, characterized by the initial feeling of an approaching episode, still able to keep down oral medication. Emetic or vomiting phase is characterized as intense persistent nausea, and repeated vomiting typically lasting hours to days. Recovery phase is typically the phase where vomiting ceases, nausea diminishes or is absent, and appetite returns. "Cyclic vomiting syndrome (CVS) is a rare abnormality of the neuroendocrine system that affects 2% of children." This disorder is thought to be closely related to migraines and family history of migraines.

<span class="mw-page-title-main">Aprepitant</span> Chemical compound

Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and dexamethasone. It is taken by mouth or administered by intravenous injection.

<span class="mw-page-title-main">Nabilone</span> Synthetic cannabinoid

Nabilone, sold under the brand name Cesamet among others, is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It mimics tetrahydrocannabinol (THC), the primary psychoactive compound found naturally occurring in Cannabis.

Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, and possibly dehydration. Feeling faint may also occur. It is considered more severe than morning sickness. Symptoms often get better after the 20th week of pregnancy but may last the entire pregnancy duration.

<span class="mw-page-title-main">Rumination syndrome</span> Medical condition

Rumination syndrome, or merycism, is a chronic motility disorder characterized by effortless regurgitation of most meals following consumption, due to the involuntary contraction of the muscles around the abdomen. There is no retching, nausea, heartburn, odour, or abdominal pain associated with the regurgitation as there is with typical vomiting, and the regurgitated food is undigested. The disorder has been historically documented as affecting only infants, young children, and people with cognitive disabilities . It is increasingly being diagnosed in a greater number of otherwise healthy adolescents and adults, though there is a lack of awareness of the condition by doctors, patients, and the general public.

<span class="mw-page-title-main">Levonantradol</span> Chemical compound

Levonantradol (CP 50,556-1) is a synthetic cannabinoid analog of dronabinol (Marinol) developed by Pfizer in the 1980s. It is around 30 times more potent than THC, and exhibits antiemetic and analgesic effects via activation of CB1 and CB2 cannabinoid receptors. Levonantradol is not currently used in medicine as dronabinol or nabilone are felt to be more useful for most conditions, however it is widely used in research into the potential therapeutic applications of cannabinoids.

The Rome process and Rome criteria are an international effort to create scientific data to help in the diagnosis and treatment of functional gastrointestinal disorders, such as irritable bowel syndrome, functional dyspepsia and rumination syndrome. The Rome diagnostic criteria are set forth by Rome Foundation, a not for profit 501(c)(3) organization based in Raleigh, North Carolina, United States.

<span class="mw-page-title-main">Vomiting</span> Involuntary, forceful expulsion of stomach contents, typically via the mouth

Vomiting is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.

<span class="mw-page-title-main">Nausea</span> Medical symptom or condition

Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.

Abdominal aura, also known as visceral aura and epigastric aura, is a type of somatosensory aura that typically manifests as abdominal discomfort in the form of nausea, malaise, hunger, or pain. Abdominal aura is typically associated with epilepsy, especially temporal lobe epilepsy, and it can also be used in the context of migraine. The term is used to distinguish it from other types of somatosensory aura, notably visual disturbances and paraesthesia. The abdominal aura can be classified as a somatic hallucination. Pathophysiologically, the abdominal aura is associated with aberrant neuronal discharges in sensory cortical areas representing the abdominal viscera.

Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of many cancer treatments. Nausea and vomiting are two of the most feared cancer treatment-related side effects for cancer patients and their families. In 1983, Coates et al. found that patients receiving chemotherapy ranked nausea and vomiting as the first and second most severe side effects, respectively. Up to 20% of patients receiving highly emetogenic agents in this era postponed, or even refused, potentially curative treatments. Since the 1990s, several novel classes of antiemetics have been developed and commercialized, becoming a nearly universal standard in chemotherapy regimens, and helping to better manage these symptoms in a large portion of patients. Efficient mediation of these unpleasant and sometimes debilitating symptoms results in increased quality of life for the patient, and better overall health of the patient, and, due to better patient tolerance, more effective treatment cycles.

Abdominal migraine(AM) is a functional disorder that usually manifests in childhood and adolescence, without a clear pathologic mechanism or biochemical irregularity. Children frequently experience sporadic episodes of excruciating central abdominal pain accompanied by migrainous symptoms like nausea, vomiting, severe headaches, and general pallor. Abdominal migraine can be diagnosed based off clinical criteria and the exclusion of other disorders.

<span class="mw-page-title-main">Cancer and nausea</span>

Cancer and nausea are associated in about fifty percent of people affected by cancer. This may be as a result of the cancer itself, or as an effect of the treatment such as chemotherapy, radiation therapy, or other medication such as opiates used for pain relief. About 70 to 80% of people undergoing chemotherapy experience nausea or vomiting. Nausea and vomiting may also occur in people not receiving treatment, often as a result of the disease involving the gastrointestinal tract, electrolyte imbalance, or as a result of anxiety. Nausea and vomiting may be experienced as the most unpleasant side effects of cytotoxic drugs and may result in patients delaying or refusing further radiotherapy or chemotherapy.

<span class="mw-page-title-main">Cannabis in pregnancy</span> Effects of cannabis consumption during pregnancy

Cannabis consumption in pregnancy may or may not be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits. The American College of Obstetricians and Gynecologists recommended that cannabis use be stopped before and during pregnancy. There has not been any official link between birth defects and marijuana use. Cannabis is the most commonly used illicit substance among pregnant women.

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