Cannabinoid hyperemesis syndrome: Marijuana is both antiemetic and proemetic

WHY COMPULSIVE HOT BATHING?

The mechanism behind this unique characteristic of cannabinoid hyperemesis syndrome is not known. Several theories have been suggested, but no study has identified the exact explanation for this phenomenon.^{1,9,10,13–15,17–31}

One suggested mechanism is a response by the thermoregulatory center of the brain to the dose-dependent hypothermic effects of THC, or even a direct effect of CB1 receptor activation in the hypothalamus.⁹ Cannabis toxicity could disrupt the equilibrium of satiety, thirst, digestive, and thermoregulatory systems of the hypothalamus, and this interference could resolve with hot bathing.¹

The so-called “cutaneous steal” syndrome has also been proposed, in which cutaneous vasodilation caused by hot water decreases the blood volume available for the splanchnic circulation thought to be responsible for the abdominal pain and vomiting.¹³ The compulsive hot bathing may also be a response by the brain to the anxiety or psychological stress induced by severe nausea and vomiting.¹⁴

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of cannabinoid hyperemesis syndrome includes mainly cyclic vomiting syndrome and psychogenic vomiting. A careful history is useful, as is ruling out medication-induced reactions, toxins, pregnancy, and gastrointestinal, neurologic, metabolic, and endocrine causes. All three of these vomiting syndromes can present with a cyclic pattern of nausea and vomiting. Cannabis use is common in all three and so is not helpful in differentiating them. But the characteristic compulsive hot bathing and showering is unique and pathognomonic of cannabinoid hyperemesis syndrome.³²

Endoscopic examination may reveal esophagitis and gastritis from severe bouts of retching.²⁶

Cyclic vomiting syndrome

The Rome III criteria for the diagnosis of cyclic vomiting syndrome include three or more stereotypic episodes of acute-onset nausea and vomiting lasting less than 1 week, alternating with intervals of completely normal health. The criteria should be fulfilled for the previous 3 months with symptom onset at least 6 months before diagnosis.³³

In a series of 17 patients with adult-onset cyclic vomiting syndrome,¹⁸ the average age at onset was 30, and 13 (76%) of the patients were women. Fifteen (88%) of the patients experienced a prodrome or aura of abdominal pain or headache, and in this group, a trigger such as emotional stress and infection could also be identified in 9 (60%).

Unlike in cannabinoid hyperemesis syndrome, most patients with cyclic vomiting syndrome have a family history of migraine headache, and the prevalence of psychological stressors is high.³¹ Also, patients with cannabinoid hyperemesis syndrome do not respond to medications that usually abort migraine episodes,¹⁵ whereas patients with cyclic vomiting syndrome, especially those who have a family history of migraines, may respond to antimigraine medications such as triptans. There is evidence of clinical psychological overlap between cyclic vomiting syndrome, abdominal migraine, and migraine headaches. Some authors recommend antimigraine therapy even in the absence of a family or personal history of migraine if, after a careful history and physical examination, the diagnosis of cyclic vomiting syndrome seems likely. Moreover, nonmedical management such as sleep, dark rooms, and quiet environment are not as effective in cannabinoid hyperemesis syndrome as they are in cyclic vomiting syndrome.¹⁸

Psychogenic vomiting

Psychogenic vomiting is classically defined as vomiting caused by psychological mechanisms without any obvious organic cause.¹³ It occurs most commonly in patients with major depressive disorder or conversion disorder.³⁴ The mechanism appears to be a combination of past organic or gastrointestinal functional abnormalities and emotional problems, and multiple patterns of vomiting can occur. Most of these patients can be treated with behavioral therapy, antidepressant drug therapy, and supportive psychotherapy.^34,35

ASKING A SERIES OF QUESTIONS

Most patients with cannabinoid hyperemesis syndrome have a history of frequent visits to emergency departments or clinics for persistent nausea and vomiting, and they may have undergone extensive diagnostic workups to exclude structural, inflammatory, infectious, and functional diseases of the bowel.^23,24

To prevent unnecessary testing and use of healthcare resources, Wallace et al³² proposed an algorithm to help guide clinicians in diagnosing and treating patients with suspected cannabinoid hyperemesis syndrome. A patient presenting with severe nausea and vomiting should prompt a series of questions:

Do the signs and symptoms suggest a severe underlying medical cause? If so, this should be pursued.

Do symptoms improve while taking a hot shower or bath? If not, pursue an appropriate diagnostic evaluation and treatment for conditions other than cannabinoid hyperemesis syndrome.

Is the bathing compulsive? If not, consider other diagnoses, but remain suspicious about cannabinoid hyperemesis syndrome.

Does the patient currently use cannabis daily or almost daily, and has the patient done so for at least the past year? If the patient denies using cannabis, a urine drug screen for THC may be useful. If the patient admits to use, a presumptive diagnosis of cannabinoid hyperemesis syndrome can be made.

Does the patient have signs or symptoms of volume depletion, or is the patient unable to tolerate oral hydration? Encourage oral hydration or provide intravenous hydration, and provide cannabis cessation counseling.

Do the symptoms improve? If yes, great! Provide cessation counseling, resources, and follow-up. If not:

Is the patient still using cannabis? If not, it is time to rethink the diagnosis.

Treatment in the acute setting is supportive and includes intravenous hydration and correction of electrolytes. Conventional antiemetics such as ondansetron, metoclopramide, prochlorperazine, and promethazine have not been effective in relieving hyperemesis.^9,12,14 This implies that the mechanism of emesis likely does not involve dopaminergic and serotonin pathways in the central and autonomic nervous systems.

Cessation of cannabis use is key for long-term resolution of symptoms. Efforts should be made to provide counseling and encourage patients to stop using the drug entirely (Figure 1).

SOMETHING TO THINK ABOUT

With the high prevalence of chronic cannabis abuse and the recent legalization of recreational marijuana use, we will all likely encounter a patient with cannabinoid hyperemesis. With adequate knowledge of this phenomenon, we can avoid unnecessary workups and inappropriate medical and surgical treatment in patients presenting with recurrent vomiting of unknown cause. The diagnosis can easily be made by simply asking for a history of chronic marijuana use and symptoms related to cannabinoid hyperemesis syndrome, such as relief of symptoms with hot baths or showers and with marijuana cessation.

Conservative management and fluid resuscitation is important in the acute setting, but cessation of marijuana use and follow-up counseling are the key components for treating patients with cannabinoid hyperemesis syndrome and for preventing recurrence.