Cannabinoid Hyperemesis: High on the Differential for Intractable Vomiting

By Sarah A. Buckley & Nicholas M. Mark

Faculty Peer Reviewed

An 18-year-old male presents complaining of crampy abdominal pain, nausea, and intractable vomiting for the past year. The symptoms are episodic, lasting several weeks and remitting for weeks to months. The patient states that his abdominal pain is 10 out of 10 in severity, and that he has been vomiting up to 20 times each day. He has been evaluated at multiple hospitals, and he has had numerous upper endoscopies, colonoscopies, swallowing studies, and CT and MRI imaging studies, all of which were unrevealing. He underwent a cholecystectomy, but had no improvement in his symptoms after the surgery. His pain and nausea are unresponsive to antacids and antiemetics. The patient’s only relief is with hot water bathing: he spends hours each day in the shower with the temperature set as hot as he can bear. The patient’s history is otherwise unremarkable, except that he admits to daily marijuana use beginning at the age of 14.

This patient’s story is typical of cannabinoid hyperemesis, a clinical syndrome characterized by intractable vomiting and abdominal pain associated with the unusual learned behavior of compulsive hot water bathing, occurring in the setting of long-term heavy marijuana use. Treatment consists of medication for immediate symptomatic relief and marijuana cessation for long-term relief. Symptoms usually remit within weeks of becoming abstinent.

If this disorder is so easily diagnosed and treated, why were the patient’s past doctors confused to the point of performing what might have been an unnecessary surgery? Cannabinoid hyperemesis is a new diagnosis, first described in 2004, and currently sixteen papers on the subject have been published. Therefore, it is likely that the patient’s prior doctors had never considered this disorder. Second, the pathogenesis of cannabinoid hyperemesis is poorly understood. How can marijuana, which is used in cancer clinics as an anti-emetic, cause intractable vomiting? And why would symptoms abate in response to high temperature? The connection between marijuana, vomiting, and heat is non-intuitive, and a medical team unfamiliar with this syndrome would be hard-pressed to reach the diagnosis.

The largest study of cannabinoid hyperemesis to date was the landmark report by Allen et al in 2004 in an area of Southern Australia where marijuana use is largely decriminalized.[i] The report tracked 10 patients who presented with cyclic vomiting after 3 to 27 years of cannabis abuse and no other history of drug abuse. All but one displayed compulsive hot water bathing; the remaining patient had only experienced his symptoms for 6 months, and the authors theorize that he had not yet learned to associate hot water with symptom palliation. The 9 compulsive bathers reported that this bizarre behavior occupied hours of their days and said that their symptoms were ameliorated within minutes of bathing and returned when the water cooled. All 10 patients were counseled to cease cannabis use, and 7 did so. Within weeks of cessation, the symptoms resolved for these 7 patients; the remaining 3 patients did not cease cannabis use and continued to have cyclic vomiting and abdominal pain. After several years of abstinence, 3 patients resumed cannabis use and were hospitalized again with cyclic vomiting and abdominal pain. Once again, 2 of these patients successfully stopped using cannabis, and their symptoms resolved. The remaining patient continued to use cannabis and continued to experience symptoms at the time of publication.

Following the first case report, further cases have been described on three continents. All patients presented with the classic triad of symptoms described by Allen et al: cyclic vomiting and abdominal pain, an extensive history of cannabis abuse, and palliation with hot water bathing. The fact that this unique triad is preserved in diverse patient populations suggests that there is a pathogenic mechanism that underlies this syndrome.

Several authors have speculated about the pathophysiology of cannabinoid hyperemesis, and though the specifics remain unclear, there is consensus over some of the basic principals: It appears that the high lipophilicity of delta-9-tetrahydrocannabinol (Δ⁹-THC, the active compound in marijuana) causes cumulative increases in concentration with chronic use, which may lead to toxicity in susceptible patients.  The abdominal pain and vomiting are explained by the effect of cannabinoids on CB-1 receptors in the intestinal nerve plexus, causing relaxation of the lower esophageal sphincter and inhibition of gastrointestinal motility.[ii] This finding is supported by gastric emptying studies performed on one of the patients presented by Allen et al, which revealed severely delayed emptying. While cannabis appears to have anti-emetic effects that are centrally mediated,[iii] it is possible that these effects predominate at low doses whereas the gastrointestinal effects predominate at the high concentrations that occur with long-term use.

The proposed explanation for compulsive hot water bathing is based on the fact that cannabis disrupts autonomic and thermoregulatory functions of the hippocampal-hypothalamic-pituitary system. There is a high concentration of CB1 receptors within the limbic system,[iv] and the hypothalamus in particular is known to be responsible for integrating central and peripheral thermosensory input.[v] Furthermore, Δ⁹-THC induces hypothermia in mice in a dose-dependent manner.[vi]  While this evidence links cannabis to the hypothalamus and to thermoregulation, it does not provide a causal relationship. Two mechanisms proposed by Chang et al are that (1) cannabinoid-induced hypothermia causes the desire for hot water bathing, or (2) hot water bathing is the direct result of CB1 activation in the hypothalamus. The true mechanism underlying hot water bathing remains enigmatic, and further studies are needed to elucidate the relationship between this bizarre learned behavior and the other features of cannabinoid hyperemesis.

A timely diagnosis of cannabinoid hyperemesis is essential not only to effect proper treatment but also to prevent iatrogenic morbidity and mortality from unnecessary diagnostic procedures and surgical interventions.  There are, however, several obstacles to effective diagnosis:

First, the legal status of marijuana makes eliciting an accurate drug history challenging. Second, the bizarre hot water bathing is likely often attributed to psychological conditions such as obsessive-compulsive behavior. Third, the knowledge of the anti-emetic effects of cannabis likely disguises cases of cannabinoid hyperemesis, leading to the erroneous belief that cannabis is treating cyclic vomiting rather than causing it.  Finally, the fact that this syndrome is so recently described and relatively unknown outside an esoteric subset of the GI literature means that most clinicians are unaware of its existence.  The following diagnostic criteria adapted from Sontineni et al[vii] can be used to facilitate a diagnosis of cannabinoid hyperemesis syndrome: 

ESSENTIAL FEATURES
	History of chronic cannabis use
	Nausea and cyclic vomiting over months
	Relief with cessation of cannabis use
SUPPORTING FEATURES
	Compulsive hot water bathing with transient relief of symptoms
	Colicky abdominal pain
	Exclusion of other etiologies (especially gall-bladder and pancreas)

 

In the case of the 18-year-old patient presented above, asking the open-ended question, “What makes you feel better?” followed by more focused questions regarding the temperature of the water and the history of marijuana use were sufficient to suggest the diagnosis of cannabinoid hyperemesis.  We propose that these questions be used as a screening tool for all patients presenting with cyclic vomiting.  Based on our experience and a review of the literature, we believe that these questions may be both sensitive and specific for detecting this unusual syndrome.

The patient presented in this case was counseled on his likely diagnosis. Though he was initially skeptical, giving him printouts of case reports on cannabinoid hyperemesis syndrome and discussing the etiology of the disease were sufficient to convince him of the diagnosis. He was treated symptomatically in the hospital.  Two weeks after discharge, he remains abstinent from marijuana and reports that his symptoms are improving.

Sarah A. Buckley and Nicholas M. Mark both are 4th year medical students at NYU School of Medicine

Faculty reviewed by Robert Hoffman, MD, Director NYU  Poison Control Center,  Associate Professor Departments of Medicine and Emergency Medicine, NYU Langone Medical Center

References:

 [i]. Allen JH, de Moore GM, Heddle R, Twartz JC. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut. 2004;53(11):1566-1570.

[ii]. Izzo AA, Coutts AA. Cannabinoids and the digestive tract. Handb Exp Pharmacol. 2005;(168):573-598.

[iii]. Simoneau II, Hamza MS, Mata HP, et al. The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets. Anesthesiology. 2001;94(5):882-887.

[iv]. Herkenham M, Lynn AB, Little MD, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. 1990;87(5):1932-1936.

[v]. Egan GF, Johnson J, Farrell M, et al. Cortical, thalamic, and hypothalamic responses to cooling and warming the skin in awake humans: a positron-emission tomography study. Proc Natl Acad Sci U S A. 2005;102(14):5262-5267.

[vi]. Hayakawa K, Mishima K, Hazekawa M, et al. Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism. Brain Res. 2008;1188:157-164.

[vii]. Sontineni SP, Chaudhary S, Sontineni V, Lanspa SJ. Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse. World J Gastroenterol. 2009;15(10):1264-1266.

Image courtesy of Wikimedia Commons

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