Cannabinoid hyperemesis syndrome

INTRODUCTION — Cannabinoid hyperemesis syndrome (CHS), first described in 2004, causes episodic vomiting and abdominal pain associated with prolonged, high-dose (nearly daily) cannabis use and resolves with cannabis cessation [1]. Symptoms are typically relieved by hot showers or baths. CHS is typically more common in male older adolescents and adults.

This topic discusses the epidemiology, evaluation, and management of cannabis hyperemesis syndrome. The following related content is discussed in separate topics:

●Clinical manifestations and management of cannabinoid and synthetic cannabinoid intoxication (see "Cannabis (marijuana): Acute intoxication" and "Synthetic cannabinoids: Acute intoxication")

●Cannabis use and cannabis use disorder (see "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects" and "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment")

●Cannabis withdrawal (see "Cannabis withdrawal: Epidemiology, clinical features, diagnosis, and treatment")

●Medical use of cannabis and cannabinoids (see "Medical use of cannabis and cannabinoids in adults")

EPIDEMIOLOGY — The overall prevalence of cannabinoid hyperemesis syndrome (CHS) is unknown due to lack of definitive criteria or diagnostic tests and occurring in a population that may not disclose substance use. In a study conducted in 2015 in a United States urban emergency department, one-third of patients with near-daily cannabis use met criteria for having had CHS in the prior six months [2]. The authors extrapolated their data to the general United States population and estimated that 2.75 million United States individuals may suffer annually from CHS.

Increased rates of CHS have been associated with the legalization and commercialization of cannabis, likely from increased use, higher tetrahydrocannabinol (THC) concentrations in cannabis products, and increased recognition of the syndrome. Since recreational cannabis legalization in Colorado, emergency department visits for cyclic vomiting and health care encounters for vomiting-related disorders have increased [3,4]. In the United States between 2005 and 2014, hospitalizations for cyclical vomiting syndromes (CVS) increased by 60 percent, and concurrent cannabis use in those hospitalized patients increased from 2 to 21 percent [5]. There was a 13-fold increase in emergency department visits for CHS in Canada over the seven years following commercialization of cannabis [6].

PATHOGENESIS — The pathogenesis of cannabinoid hyperemesis syndrome (CHS) remains unknown but may be multifactorial, involving cannabinoid metabolism, exposure dose and tolerance resulting in changes in receptor regulation, complex pharmacodynamics at the cannabinoid type 1 (CB1) receptor and other receptors both centrally and peripherally, genetics, and cannabinoid variation in plants [7-15].

Regular and prolonged cannabis use — CHS typically develops in patients with prolonged, daily cannabis use [7,16,17]. However, many individuals use cannabis daily; it is unclear why some develop CHS and others do not.

Even though CHS can occur after acute or acute-on-chronic use, most individual with CHS have reported regular cannabis use for over one year and many over at least two years [7,16,18]. Almost all patients with CHS report at least weekly cannabis use, and most report daily cannabis use (eg, three to five times per day) [17-19].

Early age of onset of cannabis use may also predispose patients to CHS. One review found that the median age of symptom onset was 24 years [7].

The route of cannabis use may also play a role. Medical visits for inhaled cannabis are more likely to be associated with CHS while visits involving edibles are more likely for acute psychiatric reactions [20].

Role of cannabinoid and TRPV1 receptors — CHS is an apparently paradoxical effect since cannabis and cannabinoid receptor agonists are known antiemetics. Nabilone and dronabinol are synthetic analogs of delta-9-tetrahydrocannabinol (THC) that have been approved by the US Food and Drug Administration (FDA) for treatment of nausea and vomiting associated with cancer chemotherapy [21-23]. CB1 receptors are involved in gastric secretion, sensation, motility, and inflammation. Stimulation of CB1 receptors by endogenous cannabinoids inhibits the hypothalamic-pituitary-adrenal axis and sympathomimetic nervous system response to stress. THC activates the CB1 receptors, non-competitively inhibits emetogenic serotonin receptors, inhibits release of serotonin via presynaptic CB1 receptors, and inhibits gastric function and proemetic dopamine activity via activation of CB1 receptors in the medulla.

Chronic cannabis use may be associated with downregulation, desensitization, or internalization of the CB1 receptor [24]. Following cessation of prolonged cannabis use, time is required for regeneration of CB1 receptors and the associated antiemetic effects. This may explain observed persistence of symptoms and gradual recovery phase in patients with CHS.

THC is also an agonist at the transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor or vanilloid receptor. TRPV1 is found in descending pain pathways that regulate antinociception and in ascending pain pathways that mediate nociception [25]. Central nervous system TRPV1 agonism by cannabinoids has potent antiemetic effects by depleting substance P [25-28]. However, overstimulation of TRPV1 from chronic cannabis use may downregulate TRPV1 and contribute to causing abdominal pain, nausea, and emesis. Additional interactions may exist between cannabinoid and TRPV1 receptors that play a role in anxiolysis and inflammation and may also contribute to CHS [29]. A genetic predisposition to CHS may exist that involves TRPV1; one small study found that patients with CHS were more likely to have mutations of TRPV1 [30]. Capsaicin is a potent agonist of TRPV1 and has been studied as a treatment for CHS. (See 'Persistent symptoms: Capsaicin, other antiemetics' below.)

THC-induced splanchnic vasodilation and cutaneous vasoconstriction ("cutaneous stealing syndrome") may be responsible for the abdominal discomfort [31]. Applying persistent heat to the skin (eg, hot showers) may reverse this syndrome and mediate an antiemetic effect by activating peripheral TRPV1, thus inducing peripheral vasodilation, redistributing blood away from the gastrointestinal tract, and mediating the complex gut-brain signaling responsible for emetic effects [25,32,33].

Cannabinoid metabolism and accumulation — Cannabinoid adipose accumulation and metabolism may contribute to CHS. Cannabinoids are lipophilic and accumulate in central and peripheral adipose tissue. Release of stored cannabinoids from fasting and lipolysis and degradation into pro-emetic agents may precipitate hyperemesis. Genetic differences in the cytochrome P450 system may be associated with accumulation of cannabinoid metabolites in predisposed individuals [30].

In a longitudinal study of patients with CHS, whole blood THC concentrations were similar during symptomatic and asymptomatic time periods [19]. However, concentrations of THC metabolites (11-hydroxy-delta-9-THC, 11-nor-9 carboxy-delta-9-THC) were higher during the asymptomatic time period, suggesting that redistribution or metabolism has a greater contribution to acute symptoms compared with simply THC concentrations. Further studies are needed to fully understand the contribution of cannabinoid metabolism and concentrations on the development of CHS.

Cannabis composition (increased THC concentrations) — Increased THC dose exposure may paradoxically be emetogenic and contribute to risk of developing CHS. Even though THC has antiemetic properties, FDA-approved medications (eg, nabilone, dronabinol) provide a relatively small daily THC dose of 1 to 6 mg [21-23]. Increased THC concentrations in cannabis products, reduction in cannabidiol (CBD) since the 1990s, and increased cannabis use and availability following legalization coincides with the increased incidence of CHS [34,35]. In the United States, the average THC concentration in cannabis strains has been gradually increasing for decades, from approximately 4 percent in 1996 to 17 percent in 2017 [34,36]. In states with legal dispensaries, the THC concentration in most herbal cannabis products was between 15 to 20 percent; some states had mean concentrations >20 percent [35,37,38]. European countries have seen a similar trend [34].

Besides THC, the cannabis plant has >400 chemicals, some of which may be emetogenic [39]. CHS has been associated with delta-8-THC use as well as other cannabinoids that are structurally similar to THC [19,40]. CHS has also been reported with synthetic cannabinoid use [41,42].

Association with cyclical vomiting syndrome — There is some clinical overlap between cyclical vomiting syndrome (CVS) and CHS, such as repetitive hot-water bathing behavior. Many adults with CVS self-medicate with cannabis to alleviate nausea [43]. Patients with classic CVS symptoms and modest, intermittent therapeutic use of cannabis are frequently mislabeled as having CHS. However, some patients with CVS-like symptoms who have a history of chronic, frequent cannabis use may actually have CHS; a trial of prolonged abstinence from cannabis can help differentiate these entities. (See "Cyclic vomiting syndrome", section on 'Chronic cannabis use'.)

Other associated factors — CHS has a male predominance, which may reflect a higher prevalence of cannabis use in males [17,18]. Mental health comorbidities, including high rates of depression and anxiety, are reported in a majority of patients with CHS [19].

CLINICAL MANIFESTATIONS

Cyclical pattern — Cannabinoid hyperemesis syndrome (CHS) causes abdominal pain, vomiting, and nausea that occurs in a cyclical pattern [17]. Patients are asymptomatic between acute episodes. Patients typically have two or more acute episodes over a six-month period.

Symptoms typically start within 24 hours of last cannabis use, which helps differentiate CHS from cannabis withdrawal (symptoms start >24 hours after use). Symptoms can occur day or night, and the onset of symptoms is random as compared with cyclical vomiting syndrome (CVS), which typically is associated with morning onset of symptoms [17]. (See "Cyclic vomiting syndrome", section on 'Clinical manifestations'.)

Acute episodes are associated with a recovery phase with gradual symptom resolution of nausea and vomiting. Acute symptoms typically resolve after cessation of cannabis use, usually after several days. However, symptoms do not always rapidly improve; in one study, several patients still had symptoms two days to two weeks after not using cannabis [17]. In another study, patients had some symptoms for 7 of the 14 days immediately following an emergency department visit for CHS, but most had returned to prior patterns of cannabis use during this time [44].

Vomiting and abdominal pain — Patients complain of severe nausea and vomiting, and most complain of abdominal pain. The emesis can be severe with up to 30 episodes daily. The pain is intense and most often diffuse, periumbilical, or epigastric [17]. Patients may be pale and diaphoretic from the pain. The intense nature of the pain also helps differentiate CHS from cannabis withdrawal.

Most patients describe normal bowel habits, but some will report diarrhea [17,45]. Some patients also report chills.

Hot-water bathing behavior — Most patients report that hot showers and/or baths relieve symptoms [19]. This can lead to compulsive bathing behavior with patients sometimes taking multiple showers daily. However, not every study has found this behavior in the majority of patients [17].

DIAGNOSTIC EVALUATION

Clinical diagnosis — Cannabinoid hyperemesis syndrome (CHS) is a clinical diagnosis. It is usually suspected in a patient with regular cannabis use (at least weekly, typically daily) and recurrent episodes of abdominal pain and vomiting, especially with hot-water bathing behavior. Diagnostic criteria (see 'Diagnostic criteria' below) can be helpful, but none are definitive. CHS is diagnosed by the resolution of symptoms upon cannabis use cessation, but other serious etiologies should be excluded, either by history (eg, prior negative evaluation for similar pain), examination, or appropriate testing.

Evaluation — The evaluation of a patient suspected of having CHS is focused on excluding other etiologies for the symptoms (eg, bowel obstruction) and/or potential complications of excessive vomiting (eg, electrolyte disturbance, acute kidney injury, Boerhaave syndrome). (See "Evaluation of the adult with nontraumatic abdominal or flank pain in the emergency department" and "Approach to the adult with nausea and vomiting".)

Since CHS involves cyclical episodes of abdominal pain, a patient who presents to care for the first time should have a thorough evaluation, even if manifestations are characteristic for CHS. This will typically include abdominal imaging since CHS can cause severe, dramatic pain. In a patient who has had multiple prior presentations with similar symptoms, a previous appropriate evaluation without an acute etiology identified, and a nonperitoneal abdominal examination, testing can be more focused and may not include imaging.

The following are reasonable tests to obtain during a visit for an acute exacerbation:

●Complete blood count with differential

●Serum electrolytes, blood urea nitrogen, and creatinine

●Serum lipase and liver enzymes

●Urinalysis

●Urine pregnancy test in a female of childbearing age

●Urine tetrahydrocannabinol (THC) metabolite immunoassay (ie, drug screen); a negative result may be helpful since it likely excludes CHS (unless the patient is only using synthetic cannabinoids, which do not cross-react with the standard urine THC immunoassay)

●Radiographic imaging if concern for esophageal or bowel perforation, cholecystitis, or bowel obstruction; choice of imaging depends upon specific concern and may include plain radiographs (eg, posteroanterior and lateral chest, supine and upright abdomen), abdominal ultrasound, or abdominal computed tomography (CT) scan

One study found that 76 percent of patients with CHS have leukocytosis and 58 percent have hypokalemia (although typically mild) [17].

Diagnostic criteria — Multiple criteria have been proposed to assist in diagnosing CHS. The Rome IV criteria is used most commonly [18]. A patient meets the Rome IV criteria if all of the following are present for the last three months with symptom onset at least six months prior to diagnosis:

●Stereotypical episodic vomiting resembling cyclic vomiting syndrome (CVS) in terms of onset, duration, and frequency (see "Cyclic vomiting syndrome", section on 'Clinical manifestations')

●Presentation after prolonged use of cannabis

●Relief of vomiting episodes by sustained cessation of cannabis use

The criteria also add that CHS may be associated with pathologic bathing behavior (ie, prolonged hot baths or showers), but this is not necessary to meet the criteria.

A subsequent proposed modification to these criteria would require at least three episodes per year, cannabis use for greater than one year before symptom onset and average use greater than four times per week, and resolution after cessation of cannabis use for at least six months or at least equal to a duration that spans three typical cycles in the patient [46].

Simonetto and colleagues proposed similar features to diagnosis CHS, including long-term and weekly cannabis use, cycling vomiting and nausea, resolution with cessation, relief of symptoms with hot bathing, and abdominal pain [47].

DIFFERENTIAL DIAGNOSIS — Many disorders can produce nausea with or without vomiting (table 1). Since individuals often self-medicate with cannabis to treat nausea and vomiting, it can be difficult to distinguish between cannabinoid hyperemesis syndrome (CHS) and a primary gastrointestinal disorder. In an adolescent or adult with recurrent episodes of vomiting and abdominal pain, the differential diagnosis is broad and include the following:

●Cyclical vomiting syndrome (CVS) and CHS are often difficult to differentiate. Both CHS and CVS are associated with recurring episodes of vomiting and repetitive hot-water bathing behavior. Many patients with CVS self-medicate with cannabis to alleviate their daily nausea and can be mislabeled as having CHS if they have only modest, intermittent cannabis use. CHS is the likely cause if symptoms resolve with a trial of prolonged cannabis abstinence. (See "Cyclic vomiting syndrome".)

●Cannabis/cannabinoid withdrawal can also cause abdominal pain, but symptoms typically take more than 24 hours to peak in intensity, the pain is less severe, and there are associated neuropsychiatric symptoms (sleep difficulty, irritability, anger, anxiety, headache, depressed mood). (See "Cannabis withdrawal: Epidemiology, clinical features, diagnosis, and treatment".)

●Recurrent intermittent small bowel obstructions can occur from adhesions or an internal hernia. During an episode, imaging would be expected to show the small bowel obstruction. (See "Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults", section on 'Recurrent intermittent obstruction'.)

●Chronic mesenteric ischemia can cause recurrent episodes of dull, crampy, post-prandial abdominal pain (ie, intestinal angina) that subsides over several hours. Patients are typically over 60 years of age and are more likely to be female rather than male. (See "Chronic mesenteric ischemia".)

●Crohn disease with proximal (ie, gastroduodenal) involvement may present with upper abdominal pain, nausea, and/or postprandial vomiting. Cross-sectional imaging (computed tomography [CT], magnetic resonance imaging [MRI]) and/or upper endoscopy would be expected to show findings consistent with inflammatory bowel disease (eg, gastric/small bowel inflammation, ulceration). (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)

●Superior mesenteric artery (SMA) syndrome can present with intermittent symptoms consistent with proximal small bowel obstruction. Patients with SMA syndrome typically have had significant weight loss (or insufficient weight gain in adolescents) leading up to onset of symptoms, and they improve when lying prone, in the left lateral decubitus, or in a knee-chest position. (See "Superior mesenteric artery syndrome".)

●Irritable bowel syndrome can cause cramping abdominal pain with periodic exacerbations. Patients tend to have alteration in bowel habits (ie, constipation and/or diarrhea) and are less likely to vomit. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)

●Cholelithiasis can cause intermittent episodes of upper abdominal pain and vomiting (ie, biliary colic), typically following consumption of a fatty meal. An abdominal ultrasound is the most sensitive modality for detecting cholelithiasis. (See "Overview of gallstone disease in adults".)

●Atypical celiac disease may present without diarrhea. Celiac disease can be differentiated by serologic evaluation and small bowel biopsy. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults", section on 'Atypical celiac disease' and "Diagnosis of celiac disease in adults".)

●Nausea and vomiting of pregnancy, gastroparesis, gastroesophageal reflux, gastric outlet obstruction, eosinophilic gastroenteritis, chronic idiopathic intestinal pseudo-obstruction, rumination syndrome, and functional nausea and vomiting disorders are reviewed separately. (See "Approach to the adult with nausea and vomiting", section on 'Chronic disorders'.)

●Acute intermittent porphyria causes frequent, recurrent attacks that typically include abdominal pain, vomiting, and sensory and motor neuropathy. Urinary porphyrin precursors and porphyrins are elevated during attacks. (See "Acute intermittent porphyria: Pathogenesis, clinical features, and diagnosis".)

MANAGEMENT

Acute episode — Acute treatment consists of symptomatic care including intravenous (IV) fluid hydration and antiemetic therapy [48,49]. A standard antiemetic (eg, ondansetron, metoclopramide) is often initially administered but is typically ineffective. We discourage administering opioids given the risk of long-term adverse effects (eg, tolerance, dependence, opioid-induced hyperalgesia, opioid use disorder, and overdose), especially in patients with recurrent presentations for pain. (See "Risk of long term opioid use and misuse after prescription of opioids for pain".)

In a patient with abdominal pain and vomiting presumed to be from cannabinoid hyperemesis syndrome (CHS), our approach is as follows:

All patients: IV fluids, dopamine antagonists

●Provide fluid repletion (eg, 1 L of normal saline or buffered crystalloid solution such as lactated Ringer over one hour).

●We suggest administering droperidol (observational studies have used 0.625 or 1.25 mg) or haloperidol (0.05 to 0.1 mg/kg, maximum single dose 2.5 mg). Both of these medications have been found to be effective in controlling acute symptoms of CHS.

Evidence for the use of dopamine antagonists for CHS includes a trial, observational study, and case reports [50]. A trial of 33 adults with cannabis use and active emesis compared haloperidol 0.05 mg/kg, haloperidol 0.1 mg/kg, or ondansetron 8 mg as a first approach [51]. Two hours following drug administration, haloperidol more effectively improved self-rated abdominal pain and nausea compared with ondansetron (10-point visual analog scale score decrease 4.6 versus 2.3 cm, difference 2.3 cm, 95% CI 0.6-4.0 cm). Efficacy was similar between haloperidol doses, but two patients who received the higher dose had return visits for acute dystonia. Patients who received haloperidol were discharged from the emergency department faster after receiving study drug (3.1 versus 5.6 hours, difference 2.5 hours, 95% CI 0.1-5.0 hours). Haloperidol was associated with higher treatment success (54 versus 29 percent), but this finding was not statistically significant. Despite low enrollment, lower crossover rate than expected (precluding paired sample analysis), and the trial being halted early for efficacy, the results were significant with a stronger-than-anticipated effect size.

An observational study and case reports have also documented the successful use of dopamine antagonists such as haloperidol and droperidol to abort severe episodes of hyperemesis [7,52-54].

Persistent symptoms: Capsaicin, other antiemetics

●In a patient with persistent symptoms despite IV fluids and dopamine antagonist, we suggest topical capsaicin cream. We apply a cream with a concentration of 0.025 to 0.1% in a thin film over the abdomen. In our experience, it appears to be effective in treatment after initial application. It has minimal adverse effects, but some patients tend not to tolerate subsequent applications due to the skin discomfort of capsaicin. If it is effective and tolerable for a patient, capsaicin has the advantage that it can be continued at home since some symptoms can persist even with abstinence.

●We administer an antiemetic with a different pharmacologic activity than the original antiemetic, if given. Options include ondansetron, metoclopramide, prochlorperazine, and diphenhydramine, although these are often ineffective.

●A benzodiazepine (eg, lorazepam 1 mg IV) can be used as an antiemetic adjunct [55]. Benzodiazepines should be administered with caution given risk for dependence. These should not be used as first-line agents but rather as second- or third-line agents.

●In a patient refractory to all other treatments, aprepitant can be administered, but evidence is limited to one case report [56]. Aprepitant inhibits the substance P/neurokinin 1 (NK₁) receptor, which is similar to the postulated mechanism of action of capsaicin cream.

Evidence for the use of capsaicin for CHS includes a trial and many observational studies. A trial of 30 patients with CHS treated with capsaicin cream 0.1% (5 grams applied to abdomen) or placebo (moisturizing cream) found capsaicin was associated with less severe nausea 60 minutes after application (10-point visual analog scale score 3.2 versus 6.4 cm, difference -3.2 cm, 95% CI -0.9 to -5.4 cm) [57]. However, patients randomized to the capsaicin treatment had less severe nausea at baseline, and the difference at 60 minutes did not achieve significance (visual analog scale decrease 2.8 versus 2.1 cm, percent reduction 46 versus 25 percent, difference 21 percent, 95% CI -5.6 to 47.9 percent). More patients treated with capsaicin had complete resolution of nausea (29 versus 0 percent, relative risk 3.4, 95% CI 1.6-7.1) and no further episodes of vomiting after two hours (94 versus 62 percent), but the latter finding was not statistically significant. Only one patient did not tolerate capsaicin due to skin irritation.

Systematic reviews, retrospective studies, and case series have found that topical capsaicin cream is associated with an improvement in abdominal pain and emesis in patients not responsive to ondansetron or benzodiazepines [7,26,50,58-61]. It is hypothesized that capsaicin may provide relief by its potent agonism on the transient receptor potential vanilloid 1 (TRPV1). In a retrospective study of 43 patients treated for CHS in the emergency department, use of capsaicin cream decreased total medications administered and reduced opioid requirements; two-thirds of patients required no further treatment prior to discharge [62]. In a separate retrospective study of 201 patients with CHS, capsaicin cream was associated with greater efficacy for symptom relief than other treatments but was not associated with lower rates of admission or return emergency department visits within 24 hours [63].

Long-term management — We advise all patients with CHS to forego further cannabis use and offer mental health or substance use treatment referral. A systematic review found that symptoms completely resolved in 97 percent of patients following stopping cannabis use [7].

The patient must understand that it may take several weeks of cannabis abstinence for symptoms to resolve and that symptoms may worsen or return if cannabis is resumed. However, it is often difficult for patients to abruptly abstain from cannabis use since CHS often occurs in patients with cannabis use disorder and many will develop a withdrawal syndrome [19,64]. For these patients, the clinician can advise use of products with decreased tetrahydrocannabinol (THC) concentrations and reduced frequency of use with an ultimate goal of abstinence. However, it is unknown if reduction of use (instead of abstinence) prevents CHS recurrence. Management of cannabis withdrawal and cannabis use disorder are discussed separately. (See "Cannabis withdrawal: Epidemiology, clinical features, diagnosis, and treatment" and "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment".)

For patients with protracted symptoms who present repeatedly to the emergency department with frequent vomiting and retching, it is reasonable to individualize treatment, which may involve earlier or primary use of droperidol or haloperidol to control symptoms. An evaluation to exclude other etiologies of symptoms or complications of repeated vomiting are still appropriate in these patients, especially those whose symptoms are poorly controlled. Home use of capsaicin cream, if initially effective and tolerable, is another option for patients with persistent symptoms.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

The Partnership at Drugfree.org maintains a drug guide for 40 commonly misused drugs including common slang terms.

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cannabis use disorder and withdrawal" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Cannabis hyperemesis syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical manifestations – Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic abdominal pain, vomiting, or nausea in older adolescents and adults with chronic cannabis use. Relief of symptoms with hot showers or baths is a common feature. (See 'Clinical manifestations' above.)

●Evaluation – We perform laboratory and/or imaging studies to exclude other etiologies or to identify complications of excessive vomiting. (See 'Diagnostic evaluation' above.)

●Diagnosis – CHS is a clinical diagnosis. It is usually suspected in a patient with regular cannabis use and recurrent episodes of severe abdominal pain and vomiting, especially with hot-water bathing behavior. CHS is diagnosed by the resolution of symptoms upon cannabis use cessation, but other serious etiologies should be excluded either by history (eg, prior negative evaluation for similar pain), examination, or appropriate testing. (See 'Diagnostic evaluation' above.)

The Rome IV diagnostic criteria can assist in diagnosing CHS. All of the following need to be present for the last three months with symptom onset at least six months prior to diagnosis (see 'Diagnostic criteria' above):

•Stereotypical episodic vomiting resembling cyclic vomiting syndrome (CVS) in terms of onset, duration, and frequency

•Presentation after prolonged use of cannabis

•Relief of vomiting episodes by sustained cessation of cannabis use

●Management of acute episode – We provide symptomatic care and intravenous (IV) fluids. In a patient with abdominal pain and/or vomiting presumed from CHS, we suggest administering droperidol or haloperidol instead of other antiemetic agents (Grade 2C). The droperidol dose is 0.625 or 1.25 mg and the haloperidol dose is 0.05 to 0.1 mg/kg, maximum single dose 2.5 mg. Other antiemetics such as ondansetron can be used, although they are typically ineffective. (See 'All patients: IV fluids, dopamine antagonists' above.)

In a patient with persistent symptoms, we suggest topical capsaicin cream (Grade 2C). We apply a cream with a concentration of 0.025 to 0.1% in a thin film over the abdomen. (See 'Persistent symptoms: Capsaicin, other antiemetics' above.)

●Long-term management – We advise all patients with CHS to forego further cannabis use and offer mental health or substance use treatment referral. The patient must understand that it may take several weeks of cannabis abstinence for symptoms to resolve, and only abstinence will prevent recurrence. In a patient who cannot abruptly abstain, we advise use of products with decreased tetrahydrocannabinol (THC) concentrations and reduced frequency of use with an ultimate goal of abstinence. (See 'Long-term management' above.)