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Cannabinoid hyperemesis syndrome: a case series.

Introduction

In 2010, 17.4 million Americans were estimated to be using marijuana, and 4.6 million were using the drug on a daily basis. (1) Marijuana has long been thought of as an anti-emetic, leading many groups to advocate for the legalization of the drug for medical use. Sixteen states have already legalized the use of medical marijuana. In California alone, there is estimated to be over 750,000 medical marijuana users. (2) However, with the increasing prevalence, there have been reports over the last decade of a cyclic vomiting syndrome which is actually associated with excessive marijuana use.

Cyclic Vomiting Syndrome is defined as recurrent episodes of vomiting with normal periods of health in between episodes. (3) There appears to be a subset of patients with cyclic vomiting associated with marijuana use. The disease has been coined Cannabinoid Hyperemesis Syndrome (CHS). It was first described in 2004 by an Australian group of investigators who described 10 patients with the syndrome. The clinical features are (1) long term, excessive use of marijuana; (2) cyclical vomiting pattern that often begins years after initiation of the drug; (3) compulsive hot showering with symptom relief; and (4) resolution of symptoms with abstinence from marijuana. (4) We present a case series of four patients that we have encountered over the span of 1 year at our tertiary care institution in the hopes of educating other physicians of this underrecognized syndrome. Two of the four patients had extensive and potentially unnecessary diagnostic evaluations and interventions, including surgery, which could have been avoided if the diagnosis was made earlier in their clinical course.

Case Series

Patient #1

Patient #1 was a 28 year old white male who presented to our general medicine clinic for a second opinion in regards to his cyclic abdominal pain and vomiting. His symptoms had been ongoing for the last four years. He had accompanied nausea and vomiting. The episodes occurred every few months and lasted for several weeks at a time. The patient had undergone a Nissen Fundoplication for what was presumed to be intractable GERD. He went on to have a cholecystectomy which again did not relieve his symptoms.

During the patients evaluation he was found to have normal labs. Porphyria panel was also negative. The patient had multiple CT scans and abdominal films as well as EGD with small bowel biopsy and colonoscopy. All results were negative.

Further history revealed that the patient had been smoking marijuana since the age of 17. He smoked on average three joints daily. The only thing that relieved his symptoms were hot showers. The patient was counseled that he should abstain from marijuana. However, he has continued his chronic use of the drug. He continues to have cyclic episodes of abdominal pain and vomiting.

Patient #2

Patient #2 is a 32 year old African American male who has been hospitalized at our facility twenty four times in the last two years. He presented with cyclic episodes of vomiting and abdominal pain. He was also observed to take multiple hot showers which subjectively relieved his symptoms.

Diagnostic workup included imaging studies (CT scans, plain films, and abdominal ultrasounds) which were always negative. Laboratory testing on multiple occasions were always normal except for minor elevations in creatinine due to volume depletion, which responded quickly to fluid resuscitation each time. Urine drug screens were persistently positive for marijuana.

In regards to his marijuana use, the patient had been smoking marijuana since age 19. He smoked up to 2-3 times daily. He struggled considerably with abstaining. He continues to use cannabis and continues to present with the same symptoms despite frequent counseling.

Patient #3

Patient #3 is a 23 year old white female with ten days of epigastric pain and vomiting. She had three previous episodes in the past. The patient's symptoms were improved with hot showers. She was admitted for IV hydration.

Diagnostic work up included radiographic imaging (CT scans and plain films) which was negative. Basic labs were normal. She did have mild elevation of amylase to 144 and lipase to 92, both of which normalized the following day. This was likely due to her persistent vomiting.

The patient had a history of chronic marijuana use since the age of 15. She was smoking three times daily on average. The patient was educated on the syndrome and planned to quit upon discharge. However, she was readmitted for the same symptoms two months later and it was found that she had resumed her heavy use of marijuana.

Patient #4

Patient #4 is a 21 year old male who presented with two days of abdominal pain and vomiting. He had two similar episodes which had occurred in the past six months. This was his second hospitalization. During his stay, nursing found him to be in the shower each time they went to assess him. He stated that hot showers relieved his symptoms but they quickly returned when he came out.

Diagnostic imaging studies were negative. Basic labs were also normal. He improved after 2 days of IV fluids.

The patient had a history of marijuana use since the age of 13. He smoked at least three times daily, often more. Both the patient and his parents were educated about CHS and the importance of abstaining from marijuana. The patient has abstained since that time and has had no further episodes.

Please refer to Table 1 and Table 2 for a summary of the patient characteristics and diagnostic tests.

Discussion

These four patients likely represent a larger group with CHS which has gone undiagnosed. Patient #1 has had significant morbidity from his symptoms including multiple hospitalizations and poor quality of life. He has had multiple unnecessary diagnostic tests performed and has undergone major surgical intervention for the symptoms with no relief. Although, there was a significant delay in diagnosis of CHS, the patient also has not stopped his marijuana use and still has recurrent symptoms. We also see in patient #2, significant morbidity and repeated hospitalizations due to CHS. The patient has acknowledged the connection of his disease to chronic marijuana use, but still has been unable to stop.

CHS was first described in 2004 by an Australian group of physicians who noticed similar symptoms in 10 patients with chronic, long term marijuana use. They described the patients as having cyclic vomiting and abdominal pain. They also found that most of the patients had the peculiar finding of compulsive hot showering which relieved their symptoms. They were able to follow the 10 patients and found that only those who abstained from marijuana had relief of symptoms. (4) There have been additional case reports which have demonstrated the same symptomatology. These case reports have documented 45 patients with a mean age of 31 years. Of the patients that were followed, 40 abstained from marijuana for an extended period of time and all had symptom resolution. Seven of those patients relapsed and had return of their symptoms with recurrent marijuana use. (5-13) Many questions remain about CHS in regards to the pathology and mechanism of the disease. There has been little more than hypothesized answers to these questions. The first question is why would cannabinoids, which have previously been shown to have anti-emetic effects, (14) cause a pro-emetic disease? The answer may lie with the lipophilic nature and long half life of the chemical. (4) All the patients had excessive use which began at a young age. This may result in accumulation to the point of toxicity in genetically susceptible patients. In addition, the CB-1 receptors which mediate the anti-emetic effect of cannabinoids centrally are also present in the enteric plexus. However, activation of the enteric receptors causes decreased peristalsis and intestinal secretions which may lead to the pain and nausea. (4)

The other main question is in regards to the bizarre behavior of compulsive hot showering. It has previously been demonstrated that cannabinoids affect the limbic system of the brain. Cannabinoid toxicity may disrupt the balance of satiety, digestion, and thermoregulation and the disruption may settle with hot showers. (4) Another hypothesis is that hot showers redistribute blood from the splanchnic circulation to the skin. This temporarily relieves the chronic stimulation occurring in the CB-1 receptors of the gut resulting in symptom relief. (13) Obviously more research is needed at the biochemical level to elucidate the molecular pathways.

The purpose of this case series is to alert other physicians to the disease. It is important to recognize the symptoms of CHS in order to prevent unnecessary diagnostic testing and procedures as well as to hopefully "cure" the disease by educating the patient to stop smoking marijuana. Although important to avoid repeated diagnostic testing, it is still essential to rule out other acute causes of the symptoms. In patients presenting with recurrent episodes of vomiting, it is appropriate to ask if hot showers relieve the symptoms. Previous authors have recommended asking "have you ever tried marijuana to relieve the nausea?" which may uncover a history of chronic marijuana use. (15) This disease also raises the question of whether a urine drug screen should be added to the initial evaluation of patients with Cyclic Vomiting Syndrome. We recommend continued counseling to abstain from marijuana when the diagnosis is made. This may be the most difficult aspect of treating the disease since these patients are often physically and psychologically addicted to the drug. (16) We emphasize the importance of assisting cessation and educating the patients about CHS in order to avoid continued hospitalizations and unnecessary testing.

References

(1.) Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings. Available at: http://oas. samhsa.gov/NSDUH/2k10NSDUH/ 2k10Results.htm#2.13. Accessed September 29, 2011.

(2.) Medical Marijuana Patient Population in California. Available at: http://www. canorml.org/news/cbcsurvey2011. html#FN01. Accessed September 29, 2011.

(3.) Li BU, Lefevre F, Chemlimsky GC, et. al. North American Society for Pediatric Gastroenteroloy, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47:379.

(4.) Allen J, de Moore G, Heddle R, Twarz J. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut 2004; 53:1566-1570.

(5.) Wallace EA, Andrews SE, Garmany CL, Jelley MJ. Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South Med J 2011; 104(9):659-64.

(6.) Bramstedt J and DiBmann R. Cannabinoid hyperemesis syndrome inducing acute prerenal failure and electrolyte disturbance. Dtsch Med Wochenschr 2011; 136(34/35):1720-1722.

(7.) Bonnet U, Chang DI, Scherbaum N. Cannabis Hyperemesis Syndrome. Fortschr Neurol Psychiatr 2011; Epub ahead of print.

(8.) Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc 2011; 111(3):166-9.

(9.) Lieb M, Palm U, Nicolaus M, Reibke R, Baghai TC. Cannabinoid-induced hyperemesis. Psychiatr Prax 2011; 38(3):147-9.

(10.) Stuijvenberg MP, Ramaekers GM, Bijpost Y. Cannabinoid hyperemesis syndrome. Ned Tijdschr Geneeskd 2011; 155:A2880.

(11.) Schmid SM, Lapaire O, Huang DJ, Jurgens FE, Guth U. Cannabinoid hyperemsis syndrome: an underreported entity causing nausea and vomiting of pregnancy. Arch Gynecol Obstet 2010 [Epub ahead of print]

(12.) Miller JB, Walsh M, Patel PA, Rogan M, Arnold C, Maloney M, Donnino M. Pediatric cannabinoid hyperemesis : two cases. Pediatr Emerg Care 2010; 12:919-20.

(13.) Patterson D, et. al. Cannabinoid Hyperemesis and Compulsive Bathing: A Case Series and Paradoxical Pathophysiological Explanation. J Am Board Fam Med; 2010; 23(6):790-93.

(14.) Parker LA, Rock EM, Limebeer CL. Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol 2011; 163(7):1411-22.

(15.) Sullivan S. Cannabinoid Hyperemesis. Can J Gastroenterol 2010; 24(5):284; 285.

(16.) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision, American Psychiatric Association, Washington, DC 2000.

Sarah Sofka, MD

Assistant Professor, Department of Internal Medicine,

West Virginia University

Nathan Lerfald, MD

Assistant Professor, Program Director, Department of

Internal Medicine, West Virginia University

Corresponding author: Sarah Sofka, MD, PO Box 9160, Department of Medicine, RCBHSC, West Virginia University, Morgantown, WV 26506; ssofka@hsc.wvu.edu
Table 1. Characteristics of each patient in case series

Patient    Age    Sex       Race     Duration    Relief
                                        of       with Hot
                                     Illness     Showers

   #1      28     Male     White       4 yrs       Yes
   #2      32     Male    African      2yrs        Yes
                          American
   #3      23    Female    White        1yr        Yes
   #4      22     Male     White       6 mo        Yes

Patient    Hospitalizations    Age at first    Average     Abstinence
              In the last       Marijuana       daily         from
                 1 yr              Use        Marijuana    Marijuana
                                                 Use

   #1             10                17           1-3           No
   #2             12                19           2-3           No

   #3              1                15            3            No
   #4              2                13            3           Yes

Patient    Resolution
               of
            Symptoms

   #1          No
   #2          No

   #3          No
   #4          Yes

Table 2. Diagnostic testing results and procedures performed on
patients from case series. Lab values are from the patients' first
encounters at our institution. Radiographic testing and procedures
were performed at any point in the patients' illness.

Patient                Labs                      Imaging
                                                  Study         Result

#1        WBC 8.1; Hg 15; Platelets 268     CT abdomen and      Normal
          Na 136; K 3.5; Cl 102; Bicarb     pelvis
          25; BUN 17; Creatinine 0.8;       (performed
          glucose 102 Bili 0.2; AST 28;     between 5-10
          ALT 44; Alkp 56; GGT 29;          times)
          amylase 54; lipase 21
          Celiac Panel: Negative            RUQ U/S (c)         Normal
          Porphyria Panel: Negative
          U/A (A): negative
          UDS (B): positive for
          cannabinoids                      Plain abdominal     Normal
                                            xray

#2        WBC 5.6; Hg 12.8; Platelets       CT abdomen and      Normal
          365 Na 144; K 3.3; Cl 105;        pelvis
          Bicarb 28; BUN 5; Creatinine
          0.9; Glucose 85 Bili 0.6; AST     RUQ U/S             Normal
          20; ALT 14; Alkp 82; GGT 20;
          amylase 126; lipase 126           Plain abdominal     Normal
          U/A negative                      xray
          UDS: positive for
          cannabinioids

#3        WBC 8.2; Hg 14; Platelets 266     CT abdomen and      Normal
          Na 139; K 3.9; Cl 110; Bicarb     pelvis
          23; BUN 8; Creatinine 0.58;
          Glucose 101 Bili 1; AST 28;       RUQ U/S             Normal
          ALT 26; Alkp 48; GGT 17; LDH
          187; amylase 144; lipase 92       Plain abdominal     Normal
          Urine Pregnancy: negative         xray
          U/A: negative
          UDS: positive for
          cannabiniods

#4        WBC 16.7; Hg 15; Platelets 277    CT abdomen and      Normal
          Na 142; K 3.9; Cl 106; Bicarb     pelvis
          23; BUN 17; Creatinine 1.16;
          Glucose 134 Bili 1.6; AST 39;     RUQ U/S             Normal
          ALT 28; Alkp 82; amylase 33:
          lipase 27                         Plain abdominal     Normal
          U/A: Negative                     xrays
          UDS: Positive for
          cannabinoids                      Fluroesophagram     Normal

Patient                Labs                         Procedures

#1        WBC 8.1; Hg 15; Platelets 268     Nissen Fundoplication
          Na 136; K 3.5; Cl 102; Bicarb
          25; BUN 17; Creatinine 0.8;       Cholecystectomy
          glucose 102 Bili 0.2; AST 28;
          ALT 44; Alkp 56; GGT 29;
          amylase 54; lipase 21
          Celiac Panel: Negative            EGD with small bowel
          Porphyria Panel: Negative         biopsy with normal
          U/A (A): negative                 findings
          UDS (B): positive for
          cannabinoids                      Colonoscopy with normal
                                            findings

#2        WBC 5.6; Hg 12.8; Platelets
          365 Na 144; K 3.3; Cl 105;
          Bicarb 28; BUN 5; Creatinine
          0.9; Glucose 85 Bili 0.6; AST
          20; ALT 14; Alkp 82; GGT 20;
          amylase 126; lipase 126
          U/A negative
          UDS: positive for
          cannabinioids

#3        WBC 8.2; Hg 14; Platelets 266     EGD with normal findings
          Na 139; K 3.9; Cl 110; Bicarb
          23; BUN 8; Creatinine 0.58;
          Glucose 101 Bili 1; AST 28;
          ALT 26; Alkp 48; GGT 17; LDH
          187; amylase 144; lipase 92
          Urine Pregnancy: negative
          U/A: negative
          UDS: positive for
          cannabiniods

#4        WBC 16.7; Hg 15; Platelets 277
          Na 142; K 3.9; Cl 106; Bicarb
          23; BUN 17; Creatinine 1.16;
          Glucose 134 Bili 1.6; AST 39;
          ALT 28; Alkp 82; amylase 33:
          lipase 27
          U/A: Negative
          UDS: Positive for
          cannabinoids

(A)U/A: urinalysis

(B)UDS: urine drug screen

(C)RUQ U/S: right upper quadrant ultrasound
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Title Annotation:Scientific Article
Author:Sofka, Sarah; Lerfald, Nathan
Publication:West Virginia Medical Journal
Article Type:Case study
Date:May 1, 2013
Words:2646
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