Cannabinoid Hyperemesis Syndrome

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Diagnosis and reasoning

This young man has presented with persistent nausea, vomiting, and abdominal pain; at first glance, the list of potential etiologies is wide, encompassing diseases of the chest and abdomen, as well as a variety of metabolic and endocrine conditions. Note however, one particular oddity in the history - relief of the abdominal pain following warm showers; in a patient with an extensive history of cannabis use, this is strongly suggestive of cannabinoid hyperemesis syndrome (CHS). It is important to appreciate that the negative urine drug screen does not exclude this possibility; even after complete cessation of cannabis abuse, symptoms may persist for weeks. His differential diagnosis should not stop at this point though; it is still important to consider the potentially lethal conditions which could present in this manner. Thus, when the examination findings of tenderness in epigastric region are considered as well, the possibilities of gastric outlet obstruction, acute or chronic cholecystitis, recurrent acute pancreatitis and rarely, mesenteric ischemia raise their heads. Gastric outlet obstruction can give rise to vomiting unresponsive to antiemetic therapy; however, in this patient, the absence of hyperdynamic bowel sounds or abdominal distension makes this unlikely. The normal liver and pancreatic enzyme assays and ultrasound abdomen make cholecystitis and pancreatitis less likely. Mesenteric ischemia cannot be excluded via clinical findings or basic investigations alone; however, there are no obvious risk factors for the condition, and this is probably best considered if CHS is excluded. Last but not least, it should also be kept in mind that opiate withdrawal is another important cause of vomiting unresponsive to antiemetics; however, the absence of other supportive clinical signs and the negative urine drug screen make this possibility unlikely. He is obviously dehydrated, mandating urgent fluid resuscitation; note that the intravenous route is probably best, given the presence of vomiting. A electrolyte and renal function assay is also essential; the former reveals hyponatremia and hypochloremia which is compatible with the history of prolonged emesis. Note also the increased blood urea nitrogen: creatinine ratio; this suggests a prerenal etiology, i.e. decreased renal perfusion to control the hyponatremia associated with volume depletion. Thus, dialysis is not required, as the renal functions will normalize following correction of his fluid status. While an antiemetic such as ondansetron should also be administered, it is important to note that in general, antiemetics have only limited efficacy in CHS. Last but not least, cessation of cannabis use is key to his recovery; drug use and abuse counselling is important in this regard.


Discussion

Cannabinoid hyperemesis syndrome (CHS) is characterised by recurrent episodes of emesis and colicky abdominal pain, in the context of chronic cannabis usage. The average age of onset ranges from 16 to 51 years, with a mean age of 25.6 years; approximately 95% of patients were reported to have consumed cannabis daily for an average of 9.8 years before the onset of symptoms. Considering the pathophysiology, it is interesting to note that cannabis is used as an antiemetic for chemotherapy associated nausea, and as an appetite stimulant for anorexia in HIV positive patients. While the pathogenesis of the paradoxical hyperemesis of CHS is unclear, several mechanisms have been proposed. One mechanism is that prolonged cannabinoid use results in sequestration of cannabis in the fat, resulting in prolonged cannabinoid half-life and increased cannabinoid type 1 (CB1) receptor stimulation. Another is that prolonged cannabinoid use results in delayed gastric emptying, giving rise to the characteristic symptoms of CHS. These patients typically present with multiple episodes of hyperemesis occurring in a cyclical manner; each episode encompasses several weeks, and can be divided into 3 phases, - the prodromal or pre-emetic phase, - the vomiting phase and - the recovery phase. The prodromal phase typically consists of 1 to 2 weeks of nausea in the mornings, occasional vomiting, fear of vomiting, food aversion and colicky abdominal discomfort. Eating patterns are usually preserved, but weight loss may occur. The vomiting phase is characterised by severe nausea, frequent vomiting, abdominal pain and compulsive bathing for temporary relief (in most patients). Cessation of cannabis use results in the recovery phase, where symptoms resolve within 12 hours to 3 weeks. Note that compulsive bathing in hot water for symptomatic relief is hypothesised to be due to the proximity of CB1 receptors to the thermoregulatory center in the hypothalamus, resulting in counteraction of CB1 stimulation with warm bathing. An alternative hypothesis is based on the ability of cannabinoid receptors in the splanchnic circulation to cause vasodilation; stimulation of these receptors via warm baths results in "cutaneous steal syndrome", i.e. redistribution of blood flow from splanchnic circulation to the skin, resulting in relief of symptoms. Patients with CHS may also manifest polydipsia, weight loss (which could be as high as 4.5 - 7 kg over several weeks), mild fever and orthostasis. Although laboratory studies are usually reported to be normal, mild leukocytosis, hypokalemia, hypochloremia, elevated salivary amylase levels, delayed gastric emptying time, and mild gastritis on esophagogastroduodenoscopy have all been reported during acute episodes. The diagnosis should be suspected in patients with a history of prolonged heavy cannabis use who manifest supportive symptoms and signs; this should be followed by basic investigations aiming to exclude other causes of nausea and vomiting, i.e. a complete blood count, basic metabolic panel, liver functions, serum amylase and lipase, urinalysis, urine toxicology screen, pregnancy test, and abdominal radiographs. The management of CHS can be divided into treatment of the hyper-emetic stage, and prevention of relapses. The treatment of acute hyer-emetic episodes is primarily supportive, and requires fluid and electrolyte replacement. Note that intravenous fluid therapy may be necessary, as these patients often vomit out oral fluids. Note that most standard antiemetics, including dopamine (D2) receptor antagonists, serotonin (5-HT3) receptor antagonists and H1 receptor antagonists are largely ineffective in the management of the emesis seen in these patients; however, this should not preclude antiemetic therapy, as some relief (no matter how small) is better than none. While narcotics have been used in several cases to relieve associated abdominal pain, caution should be used in prescribing these medications, as opioids have the potential to exacerbate the nausea and vomiting. As these patients may experience associated esophagitis and gastritis of varying grades, acid suppression therapy with medications such as proton pump inhibitors are also recommended. The vomiting phase of CHS typically lasts for 24 to 48 hours, with a high risk of relapse if the patients return to cannabis usage. In this respect, it should be noted that more than few patients with CHS mistakenly increase their cannabis use, under the assumption that it will provide an antiemetic effect (similar to that in patients on chemotherapy). Thus, proper patient education is a must, with particular emphasis on the paradoxical nature of symptoms in CHS. Furthermore, these patients may benefit from referral to drug rehabilitation centers, and from outpatient treatment with cognitive behavioural therapy and motivational enhancement therapy; all of these are of proven efficacy in reducing relapses.


Take home messages

  1. Cannabinoid Hyperemesis Syndrome (CHS) is characterized by recurrent emetic episodes and chronic abdominal pain in context of cannabis usage.
  2. Temporary relief of symptoms following a warm bath is almost pathognomonic of CHS.
  3. The diagnosis of CHS requires exclusion of other cause of emesis; this can usually be performed via basic investigations.
  4. Proper patient education is a must for prevention of relapses.

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