Marijuana induced hyperemesis: a case report.
Abstract: Marijuana induced hyperemesis is a syndrome manifested by intractable nausea, vomiting and abdominal pain in someone who chronically uses marijuana with relief obtained from excessive bathing. This case report documents the exhaustive and costly work-up that has been performed in the case of one patient presenting to our facility with these complaints. It will also discuss marijuana induced hyperemesis syndrome in an effort to increase awareness of this under-diagnosed condition allowing for a more thorough history-taking and reduce unnecessary testing and radiologic examinations.
Article Type: Case study
Subject: Nausea (Causes of)
Nausea (Case studies)
Marijuana (Complications and side effects)
Drug abuse (Health aspects)
Drug abuse (Case studies)
Authors: Gessford, Amy Kathryn
John, Molly
Nicholson, Bobbi
Trout, Rachael
Pub Date: 11/01/2012
Publication: Name: West Virginia Medical Journal Publisher: West Virginia State Medical Association Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 West Virginia State Medical Association ISSN: 0043-3284
Issue: Date: Nov-Dec, 2012 Source Volume: 108 Source Issue: 6
Product: Product Code: 7754001 Marijuana
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 310150701
Full Text: Introduction

Marijuana is the most widely used illegal drug in the United States according to the National Institute of Drug Abuse. (1) Marijuana is used medically in controlling nausea and vomiting, especially in cancer patients. (2,3) In 2004, Allen et al. reported the detrimental effects seen in a series of patients presenting with intractable abdominal pain, nausea and vomiting who had a history of chronic marijuana use. (4) This group of 10 patients not only had the same symptoms, but nine of them reported temporary relief from excessive showers/bathing. The first retrospective analysis done in the United States describing this syndrome was by Soriano-Co et al.5 who found that the average patient presenting with this cluster of symptoms (nausea, vomiting and abdominal pain) was 34.4 years old with a 19-year history of chronic marijuana use prior to initial onset. All patients obtained relief by bathing on average five times per day for 30--45 minutes. In both articles, when the patients ceased marijuana use all symptoms resolved. When marijuana was reinitiated, symptoms returned within weeks to months. (4,5)

Case presentation

A 42-year-old Caucasian female, who has routinely been seen at our institution for nausea, vomiting and abdominal pain since 2003, presented with the complaint of nausea, vomiting and abdominal pain. She stated that the symptoms occurred this time after eating four bites of ice cream. She denied any hematochezia, melena, hematemesis, constipation, diarrhea or fever. She felt her symptoms were the same as those in previous episodes. Her past medical and surgical history was significant for chronic abdominal pain, iron deficiency anemia secondary to menorrhagia, poly-substance abuse, post-traumatic stress disorder with major depressive disorder, and cholecystectomy. Social history was significant for current chronic marijuana abuse with a history of cocaine use. Her medication list included quetiapine, venlafaxine ER, diazepam, lansoprazole, sucrafate, metoclopramide, polyethelene glycol, ondansetron, MS contin, hydrocodone and gabapentin.

Her physical exam was normal except for some mild epigastric tenderness which she attributed to her excessive vomiting. Laboratory studies including a comprehensive metabolic panel, amylase, lipase, and complete blood count were normal except for anemia, which had improved since her last admission. Urine studies, including urinalysis, were normal with a urine drug screen positive for delta-9-tetrohydrocannabinol (THC), benzodiazepines and opiates. Abdominal and chest x-rays were normal.

During the course of her admission, further investigation into her history revealed chronic marijuana use. She reported that long hot showers provided the only relief for her pain and nausea. She claimed that she took so many showers that her bathroom was growing excessive amounts of mold and mildew. Research into her medical records revealed an even more disturbing fact: excessive radiation exposure and medical cost. In total, she has had in excess of 97 abdominal x-rays, eight abdominal CT scans, two abdominal MRIs, an abdominal MRA, small bowel follow-through, three gastric emptying studies, four esophagogastroduodenoscopies (EGD), and three colonoscopies. Since 2003 these tests produced two abnormal findings: (1) the two most recent gastric emptying studies at 224 and 180 minutes (gastroparesis) and (2) gastritis/duodenitis on EGD. Throughout her complete sevenyear work-up, celiac sprue, peptic ulcer disease, Barrett's esophagus, porphyrias, ischemic bowel disease, appendicitis, ulcerative colitis, Crohn's disease and H. pylori infection have been excluded. The patient's medical record indicated that since 2005 she has had 97 emergency room visits. Additionally, since 2007 she has had 42 admissions.

As was the case in her previous admissions, the patient was hydrated with intravenous fluids, diet was slowly initiated and abstinence from marijuana was encouraged. She was counseled on her new diagnosis of Cannabinoid Hyperemesis Syndrome (CHS) and the importance of abstinence. She voiced understanding and was discharged. Unfortunately, she continues to return to the hospital with the same complaint and positive urine drug screens for marijuana.

Discussion

Marijuana contains more than 60 cannabinoids with delta-9tetrahydrocannabinol being the one most studied. (4,6,7) Research has identified at least two G-protein-coupled receptors in the body for THC, labeled as cannabinoid receptor type 1(CB-1) and cannabinoid receptor type 2 (CB-2). (4,6,7) CB-2 receptors are predominantly located in immunologic tissue and are thought to have immunomodulatory effects, which have yet to be defined. (7) CB-1 receptors located in neurons of the brain, spinal cord and peripheral nervous system produce neuromodulatory effect. (4,6,7) Central CB-1 receptors in the area postrema and dorsal vagal column offer the positive side effects of cannabis used in medical marijuana. (6,7) In the myenteric and submucosal plexus, CB-1 receptor activation decreases gastric acid secretion, slows gastric emptying and slows intestinal motility. (4,6,7) The exact mechanism by which these actions occur is not completely understood, but CB-1 receptors are commonly found in conjunction with acetylcholine transferase which marks cholinergic neurons supporting the theory of CB-1 receptors in the regulation of intestinal motility. (7)

The theories behind the mechanism for the phenomenon of an antiemetic producing a pro-emetic reaction are debated. The first theory is one of toxic accumulation. THC is metabolized in the liver through the cytochrome P450 system, specifically enzymes CYP2C9, CYP2C19 and CYP3A4. (1,3,4) Certain populations may have a genetic alteration in these pathways or enzymes leading to a toxic accumulation of cannabinoid metabolites. Furthermore, because THC and its metabolites are so lipophilic, the toxic accumulation occurs in the brain leading those more sensitive to higher levels to develop hyperemesis. (2,3,4)

Another theory presented considers the imbalance between the antiemetic effects of the central nervous system and the pro-emetic effects of the peripheral nervous system. (2,3,4,5,6) Initially, the central antiemetic effects targeted by medicine dominate the system. The pro-emetic effects, including gastric emptying and intestinal motility slowing, overpower the central effects with excessive use. An average of nineteen years of abuse was documented in one study. (2,3,4,5,6) Moreover, research has found that CB-1 receptors increase in number as more cannabinoids are introduced into the system, thereby potentiating the effects in the GI tract. (4)

The most recent theory underlying excessive showering is predicated on the premise that CB-1 receptors are the most prevalent G-coupled-protein receptors located throughout the brain. These receptors have been identified throughout the hypothalamic-pituitary-adrenal (HPA) axis, (5) and scientists propose that overstimulation of these receptors may alter the thermoregulatory homeostasis. The exact mechanism remains unknown.

Conclusion

It is important that physicians be aware of Cannabinoid Hyperemesis Syndrome (CHS) (See Table 1) as lack of identification could result in costly work-ups and unnecessary radiation exposure. CHS should be a diagnosis of exclusion, and specific and adequate history-taking can lead to heightened sensitivity to this possibility. Physicians should include drug abuse history, including the duration of the abuse, keeping in mind the average time of presentation was 19 years of continued marijuana abuse. (5)

Furthermore, when a patient presents with chronic abdominal pain, nausea and vomiting with marijuana use, the information should trigger a urine drug screen (UDS) and questioning about bathing history, including whether this provides relief.

References

(1.) National Institutes of Health website: NIDA info facts: marijuana. National Institute on Drug Abuse. Available at: URL:http//www.nida.nih.gov/infofacts/ marijuana.html. Accessed on March 5 2010.

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

(3.) Davis M, Maida V, Daeninck P, Pergolizzi J. The emerging role of cannabinoid neuromodulators in symptom management. Support Care Cancer 2004; 15: 63-71.

(4.) Massa F, Storr M, Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. Journal of Molecular Medicine 2005; 83: 944-954.

(5.) Soriano-Co M, Batke M, Cappell M. The cannabis hyperemesis syndrome characterized by intractable nausea and vomiting, abdominal pain and excessive bathing associated with chronic marijuana use: a report of eight cases in the United States. Digestive Diseases and Sciences. Published 9 February 2010. Accessed on Springer.

(6.) Pertwee RG. Cannabinoids and the gastrointestinal tract. Gut 2001; 48: 859-867.

(7.) Pagotto U et al. Normal Human Pituitary Gland and Pituitary Adenomas Express Cannabinoid Receptor Type 1 and Synthesize Endogenous Cannabinoids: First Evidence for a Direct Role of Cannabinoids on Hormone Modulation at the Pituitary Level. The Journal of Clinical Endocrinology & Metabolism 2001 : 86:2687-2696.

Amy Kathryn Gessford, DO

PGY2 Internal Medicine/Pediatrics Resident

WVU--Charleston Division

Molly John, MD

Associate Professor, Department of Internal Medicine

WVU--Charleston Division

Bobbi Nicholson, PhD

Professor, Marshall University Graduate College

Rachael Trout, MA, EdL

Administrator, Department of Internal Medicine

WVU--Charleston Division
Table 1: Diagnosis of Cannabinoid Hyperemesis Syndrome (CHS)

Necessary for diagnosis    History of chronic marijuana use for years

Clinical signs of          Severe nausea and vomiting
syndrome                   Vomiting that recurs in cyclic pattern over
                           months
                           Resolution of symptoms after stopping
                           marijuana use

Supportive signs           Compulsive bathing for symptom relief
                           Abdominal pain
                           No evidence of gall bladder or pancreatic
                           inflammation
Gale Copyright: Copyright 2012 Gale, Cengage Learning. All rights reserved.