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Cannabinoid Hyperemesis: A Case Series of 98 Patients

      Abstract

      Objective

      To promote wider recognition and further understanding of cannabinoid hyperemesis (CH).

      Patients and Methods

      We constructed a case series, the largest to date, of patients diagnosed with CH at our institution. Inclusion criteria were determined by reviewing all PubMed indexed journals with case reports and case series on CH. The institution's electronic medical record was searched from January 1, 2005, through June 15, 2010. Patients were included if there was a history of recurrent vomiting with no other explanation for symptoms and if cannabis use preceded symptom onset. Of 1571 patients identified, 98 patients (6%) met inclusion criteria.

      Results

      All 98 patients were younger than 50 years of age. Among the 37 patients in whom duration of cannabis use was available, most (25 [68%]) reported using cannabis for more than 2 years before symptom onset, and 71 of 75 patients (95%) in whom frequency of use was available used cannabis more than once weekly. Eighty-four patients (86%) reported abdominal pain. The effect of hot water bathing was documented in 57 patients (58%), and 52 (91%) of these patients reported relief of symptoms with hot showers or baths. Follow-up was available in only 10 patients (10%). Of those 10, 7 (70%) stopped using cannabis and 6 of these 7 (86%) noted complete resolution of their symptoms.

      Conclusion

      Cannabinoid hyperemesis should be considered in younger patients with long-term cannabis use and recurrent nausea, vomiting, and abdominal pain. On the basis of our findings in this large series of patients, we propose major and supportive criteria for the diagnosis of CH.
      Cannabis is the most widely used illicit drug in the United States and in the world.
      • Leggett T.
      United Nations Office on Drugs and Crime
      A review of the world cannabis situation.
      The 2008 World Health Organization World Mental Health Surveys estimated that the cumulative, lifetime prevalence of cannabis use in the US population is 42% to 46%.
      • Degenhardt L.
      • Chiu W.T.
      • Sampson N.
      • et al.
      Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys.
      While cannabis is well known for its antiemetic effects, more recently, long-term cannabis use has been associated with cyclic episodes of nausea, vomiting, and abdominal pain. In 2004, Allen et al
      • Allen J.H.
      • de Moore G.M.
      • Heddle R.
      • Twartz J.C.
      Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse.
      coined the term cannabinoid hyperemesis (CH) after describing 9 patients with a cyclic vomiting illness that began in the setting of long-term cannabis use and resolved after cessation of the drug. Since 2004, 13 case reports and 3 small case series, the largest of which consisted of 9 patients, have been published in further support of CH.
      • Chang Y.H.
      • Windish D.M.
      Cannabinoid hyperemesis relieved by compulsive bathing.
      • Chepyala P.
      • Olden K.W.
      Cyclic vomiting and compulsive bathing with chronic cannabis abuse.
      • Donnino M.W.
      • Cocchi M.N.
      • Miller J.
      • Fisher J.
      Cannabinoid hyperemesis: a case series.
      • Sontineni S.P.
      • Chaudhary S.
      • Sontineni V.
      • Lanspa S.J.
      Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
      • Soriano-Co M.
      • Batke M.
      • Cappell M.S.
      The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States.
      • Wallace D.
      • Martin A.L.
      • Park B.
      Cannabinoid hyperemesis: marijuana puts patients in hot water.
      • Watts M.
      Cannabinoid hyperemesis presenting to a New Zealand hospital.
      In 2009, Sontineni et al
      • Sontineni S.P.
      • Chaudhary S.
      • Sontineni V.
      • Lanspa S.J.
      Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
      described important clinical features of CH, which included long-term cannabis use, cyclic vomiting, colicky abdominal pain, compulsive use of hot showers, and improvement of symptoms with cannabis cessation.
      Given the prevalence of cannabis use worldwide, the very recent recognition of CH, and the paucity of CH literature, it is likely that this disease is underrecognized and underdiagnosed. Lack of awareness of the disease may lead to invasive and costly diagnostic tests, as well as patient and physician frustration. To promote wider recognition and further understanding of this condition, we conducted a case series, the largest to date, of patients diagnosed with CH at our institution.

      Patients and Methods

      Inclusion criteria were determined by reviewing all PubMed indexed journals with case reports and case series on CH. On the basis of the results of that review, patients were included if they had (1) long-term marijuana use before the start of symptoms, (2) a history of recurrent vomiting, and (3) the absence of a major illness that could explain the symptoms. Using institutional software, the electronic medical record was searched from January 1, 2005, through June 15, 2010, for the terms listed in Table 1, and 101 unique patients were identified. Two of the investigators (J.H.S., D.A.S.) independently reviewed each patient record to determine study eligibility, with 97% concordance between the reviewers on assignment of eligibility. For cases in which there was no consensus, a gastroenterologist (A.S.O.) determined eligibility. Fifty-five patients met the inclusion criteria. To ensure that all eligible patients were captured, a second search was performed of all gastroenterology notes from January 1, 2005, through June 15, 2010, with the following search terms: cannabinoid OR cannabis OR marijuana AND vomiting OR emesis OR hyperemesis. From this second search, 1470 patients were identified, for a total of 1571 potentially eligible patients. Two of the investigators (J.H.S., M.L.H.) evenly divided the newly identified patient records, screened their portions independently, and met to discuss unclear cases. As a result of the second search, 43 additional patients met inclusion criteria, bringing the total to 98 patients. The medical records of these 98 patients were then reviewed by one author (D.A.S.) who abstracted demographic and clinical information.
      TABLE 1Terms Used in Initial Search of Electronic Medical Records to Identify Patients With Cannabinoid Hyperemesis
      Cannabinoid hyperemesis syndrome
      Cannabinoid hyperemesis
      Hyperemesis secondary to cannabis use
      Cannabis hyperemesis syndrome
      Cyclic vomiting secondary to chronic cannabis abuse
      Cyclic vomiting secondary to chronic marijuana abuse
      Hyperemesis secondary to marijuana abuse
      Recurrent vomiting secondary to cannabis abuse
      Recurrent vomiting secondary to marijuana abuse
      Cannabinoid hyperemesis
      Cannabinoid vomiting
      Cannabinoid emesis
      Cannabis hyperemesis
      Cannabis vomiting
      Cannabis emesis
      Marijuana hyperemesis
      Marijuana vomiting
      Marijuana emesis

      Results

      The demographic characteristics of the study population are shown in Table 2. Sixty-six patients (67%) were males, the mean ± SD age at evaluation was 32.3±9.9 years, and the mean ± SD age at symptom onset was 25.3±8.9 years (range, 14-48 years). Sixty patients (65%) had a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of 25 or less, and only 11 (12%) were obese, defined as a body mass index of greater than 30. Forty-eight patients (49%) used tobacco, but only 10 (10%) reported weekly use of alcohol.
      TABLE 2Characteristics of 98 Patients With Cannabinoid Hyperemesis
      CharacteristicValue
      Age (y), mean ± SD32.3±9.89
      Age distribution (y)
       20-3051 (52)
       31-4026 (27)
       41-5015 (15)
       ≥516 (6)
      Gender
       Male66 (67)
       Female32 (33)
      Ethnicity
       Caucasian78 (80)
       Hispanic3 (3)
       African American5 (5)
       Other12 (12)
      State of residence
       Minnesota33 (34)
       Other65 (66)
      BMI (n=93)
       ≤2025 (27)
       21-2535 (37)
       26-3022 (24)
       ≥3111 (12)
      Nicotine use
       Yes48 (49)
       No50 (51)
      Alcohol use
       Yes10 (10)
       No76 (78)
       Unknown12 (12)
      Employment status
       Employed62 (63)
       Unemployed36 (37)
      Data are presented as No. (percentage) of patients unless indicated otherwise. BMI = body mass index.
      The duration and frequency of cannabis use before symptom onset are shown in the Figure. This information was available for 37 (38%) and 75 (77%) of the patients, respectively. Twenty-five (68%) of 37 patients consumed cannabis products for more than 2 years before symptoms occurred. Forty-four patients (59%) used cannabis on a daily basis, while 71 patients (95%) used it more than once a week.
      Figure thumbnail gr1
      FIGUREDuration of cannabis use before onset of symptoms (top) and frequency of cannabis use per week (bottom).
      All patients had symptoms of nausea and vomiting, as noted in Table 3. In 53 patients (71%), the symptoms were present in the morning, while only 16 (21%) had symptoms associated with meals. Eighty-four patients (86%) had abdominal pain associated with nausea and vomiting. Among the 75 patients for whom location of pain was recorded, 46 (61%) described epigastric pain, while 17 (23%) reported a periumbilical location; the location of pain was not documented in 13 (15%) of the 84 patients who reported abdominal pain. The description of the pain varied and was described as burning, crampy, or sharp. Of 95 patients with bowel habits recorded, 64 (67%) reported normal bowel habits, while 22 patients (23%) reported diarrhea. Fifty-seven patients (58%) had documentation of the effects of hot water bathing on their symptoms; of these, 52 (91%) reported relief of their symptoms with hot showers or baths. There was no comment on the effect of bathing in hot water in 41 patients (42%), and only 5 patients (5%) specifically denied any relief with hot water bathing. Associated symptoms were reported by some patients and included diaphoresis in 20 (20%), bloating in 6 (6%), and flushing in 5 (5%). Eighty-one patients (83%) reported weight loss, with a mean loss of 14.2 kg (median, 12 kg).
      TABLE 3Clinical Manifestations of Cannabinoid Hyperemesis in 98 Patients
      SymptomNo. (%) of patients
      Nausea98 (100)
      Emesis98 (100)
      Time of symptoms (n=75)
       Morning53 (71)
       Postprandial16 (21)
       During defecation6 (8)
      Abdominal pain84 (86)
      Location of pain (n=75)
       Epigastric46 (61)
       Periumbilical17 (23)
       Diffuse4 (5)
       Other8 (11)
      Description of pain (n=48)
       Burning13 (27)
       Crampy14 (29)
       Sharp11 (23)
       Other10 (21)
      Bowel habits (n=95)
       Diarrhea22 (23)
       Constipation7 (7)
       Both2 (2)
       Normal64 (67)
      Relief with hot showers (n=57)
       Yes52 (91)
       No5 (9)
      Other symptoms
       Diaphoresis20 (20)
       Bloating6 (6)
       Flushing5 (5)
       Chills2 (2)
      Diagnostic studies were performed in most patients and yielded negative results for alternative diagnoses; these studies included complete blood cell count, glucose level, liver biochemistries, pancreatic enzyme level, abdominal computed tomography, upper endoscopy, and colonoscopy. Sixty-one patients (62%) had gastric scintigraphy performed, with normal gastric emptying documented in 28 (46%), delayed emptying in 18 (30%), and rapid emptying in 15 (25%).
      Follow-up was available in only 10 patients (10%). Three (30%) of these patients did not abstain from cannabis use and continued to have symptoms. Six patients (60%) stopped using cannabis and noted complete resolution of their symptoms. The time to improvement varied from 1 to 3 months. After not using cannabis for only 1 month, 1 patient (10%) experienced no symptomatic improvement, and no further follow-up was documented.

      Discussion

      Current knowledge of CH is based on several case reports and small case series. In fact, diagnostic clinical criteria originate from a review of only 13 cases of CH.
      • Sontineni S.P.
      • Chaudhary S.
      • Sontineni V.
      • Lanspa S.J.
      Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
      Our case series, the largest to date, confirms the essential and major criteria previously proposed by Sontineni et al
      • Sontineni S.P.
      • Chaudhary S.
      • Sontineni V.
      • Lanspa S.J.
      Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
      but additionally expands the major criteria and modifies the previously proposed “characteristics suggestive of the diagnosis.” Firstly, long-term cannabis use is essential for the diagnosis. The major features include (1) severe cyclic nausea and vomiting, (2) resolution with cannabis cessation, (3) relief of symptoms with hot showers or baths, (4) abdominal pain, and (5) weekly use of cannabis. Supportive features include (1) age younger than 50 years, (2) weight loss of greater than 5 kg, (3) morning predominance of symptoms, (4) normal bowel habits, and (5) negative findings on diagnostic evaluation. Lastly, our case series expands the general knowledge of CH.
      Our data support the previously proposed essential criterion for a diagnosis of CH: long-term cannabis use. The duration of cannabis use before onset of symptoms varied greatly in our study (ranging from 4 months to 27 years), but the majority of our patients developed symptoms within 1 to 5 years from the onset of cannabis use. Because 32% of our patients reported cannabis use for less than 1 year, we believe that years of cannabis use are not essential for the diagnosis and that CH should even be considered in patients who report nausea and vomiting after using cannabis for less than 1 year. With the exception of the case series by Soriano-Co et al,
      • Soriano-Co M.
      • Batke M.
      • Cappell M.S.
      The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States.
      which suggested that CH is preceded by many years of cannabis use, prior case reports and case series describe a distribution similar to our findings.
      • Allen J.H.
      • de Moore G.M.
      • Heddle R.
      • Twartz J.C.
      Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse.
      • Chang Y.H.
      • Windish D.M.
      Cannabinoid hyperemesis relieved by compulsive bathing.
      • Chepyala P.
      • Olden K.W.
      Cyclic vomiting and compulsive bathing with chronic cannabis abuse.
      • Donnino M.W.
      • Cocchi M.N.
      • Miller J.
      • Fisher J.
      Cannabinoid hyperemesis: a case series.
      • Sontineni S.P.
      • Chaudhary S.
      • Sontineni V.
      • Lanspa S.J.
      Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
      • Wallace D.
      • Martin A.L.
      • Park B.
      Cannabinoid hyperemesis: marijuana puts patients in hot water.
      • Watts M.
      Cannabinoid hyperemesis presenting to a New Zealand hospital.
      Our data corroborate the previously proposed major criteria of severe, cyclic nausea and vomiting, with the majority of our study's patients (70%) reporting more than 7 episodes per year. Moreover, we propose several new major diagnostic criteria for CH as shown in Table 4. Patients in our case series described frequent hot water bathing during acute attacks, which is consistent with prior reports in the literature.
      • Allen J.H.
      • de Moore G.M.
      • Heddle R.
      • Twartz J.C.
      Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse.
      • Chang Y.H.
      • Windish D.M.
      Cannabinoid hyperemesis relieved by compulsive bathing.
      • Chepyala P.
      • Olden K.W.
      Cyclic vomiting and compulsive bathing with chronic cannabis abuse.
      • Donnino M.W.
      • Cocchi M.N.
      • Miller J.
      • Fisher J.
      Cannabinoid hyperemesis: a case series.
      • Sontineni S.P.
      • Chaudhary S.
      • Sontineni V.
      • Lanspa S.J.
      Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
      • Soriano-Co M.
      • Batke M.
      • Cappell M.S.
      The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States.
      • Wallace D.
      • Martin A.L.
      • Park B.
      Cannabinoid hyperemesis: marijuana puts patients in hot water.
      • Watts M.
      Cannabinoid hyperemesis presenting to a New Zealand hospital.
      Given the fact that 91% of our patients reported that hot water relieved symptoms of nausea and vomiting and because no other known vomiting syndromes share this phenomenon, we propose this behavior as a new major criterion. In addition, our data demonstrate that patients most commonly experience epigastric or periumbilical abdominal pain, which are locations previously described in pediatric patients with cyclic vomiting syndrome (CVS).
      • Catto-Smith A.G.
      • Ranuh R.
      Abdominal migraine and cyclical vomiting.
      • Li B.U.
      • Fleisher D.R.
      Cyclic vomiting syndrome: features to be explained by a pathophysiologic model.
      Previously, colicky abdominal pain was deemed a symptom suggestive of CH; however, our data did not demonstrate a predominant pain type (Table 3). Lastly, the majority of patients reported smoking cannabis daily, but several patients reported less than once-weekly use, a finding consistent with prior reports.
      • Chang Y.H.
      • Windish D.M.
      Cannabinoid hyperemesis relieved by compulsive bathing.
      • Chepyala P.
      • Olden K.W.
      Cyclic vomiting and compulsive bathing with chronic cannabis abuse.
      • Donnino M.W.
      • Cocchi M.N.
      • Miller J.
      • Fisher J.
      Cannabinoid hyperemesis: a case series.
      • Sontineni S.P.
      • Chaudhary S.
      • Sontineni V.
      • Lanspa S.J.
      Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
      • Soriano-Co M.
      • Batke M.
      • Cappell M.S.
      The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States.
      • Wallace D.
      • Martin A.L.
      • Park B.
      Cannabinoid hyperemesis: marijuana puts patients in hot water.
      • Watts M.
      Cannabinoid hyperemesis presenting to a New Zealand hospital.
      Thus, we have added weekly use of cannabis to the major diagnostic criteria.
      TABLE 4Proposed Clinical Criteria for Cannabinoid Hyperemesis
      Essential for diagnosis
       Long-term cannabis use
      Major features
       Severe cyclic nausea and vomiting
       Resolution with cannabis cessation
       Relief of symptoms with hot showers or baths
       Abdominal pain, epigastric or periumbilical
       Weekly use of marijuana
      Supportive features
       Age less than 50 y
       Weight loss of >5 kg
       Morning predominance of symptoms
       Normal bowel habits
       Negative laboratory, radiographic, and endoscopic test results
      Several supportive criteria were evident in our case series. The first is age younger than 50 years, a phenomenon consistent with the demographic group that habitually uses cannabis.
      • Degenhardt L.
      • Chiu W.T.
      • Sampson N.
      • Kessler R.C.
      • Anthony J.C.
      Epidemiological patterns of extra-medical drug use in the United States: evidence from the National Comorbidity Survey Replication, 2001-2003.
      We believe the second supportive criterion should be weight loss because of the notable weight loss reported by our patients; however, this finding may become less common as awareness of this disease grows and patients are diagnosed earlier. The third supportive criterion, a morning predominance of symptoms, is another symptom previously described in the literature for pediatric CVS but not for CH.
      • Catto-Smith A.G.
      • Ranuh R.
      Abdominal migraine and cyclical vomiting.
      • Fleisher D.R.
      • Matar M.
      The cyclic vomiting syndrome: a report of 71 cases and literature review.
      The next supportive criterion of normal bowel habits is based on the fact that nearly two-thirds of our patients reported this feature; if patients present with a predominance of either diarrhea or constipation, CH may still be present, but additional diagnoses and testing may need to be considered. The final proposed supportive criterion of CH is failure to identify another cause of recurrent vomiting based on any testing that is performed; however, if CH is suspected before testing, we recommend that case-specific, judicious testing be performed.
      In addition to modifying existing criteria, our case series elucidates other aspects of CH. Several patients reported autonomic symptoms such as flushing and diaphoresis; these symptoms reportedly persisted for hours to days. The majority of patients experienced recurrent symptoms at intervals of less than 2 months. The severity of CH symptoms varied, and many patients required frequent hospitalizations for hydration and intravenous antiemetics.
      The pathophysiology of CH is not well understood. The antiemetic effects of cannabis and its derivatives have been recognized for some time.
      • Walsh D.
      • Nelson K.A.
      • Mahmoud F.A.
      Established and potential therapeutic applications of cannabinoids in oncology.
      Cannabinoids act mainly through 2 receptors, CB1 and CB2, which are mainly located in the central nervous system, on the dorsal ganglia, hypothalamus, hippocampus, and cerebellum
      • Croxford J.L.
      Therapeutic potential of cannabinoids in CNS disease.
      • González S.
      • Cebeira M.
      • Fernández-Ruiz J.
      Cannabinoid tolerance and dependence: a review of studies in laboratory animals.
      ; they are also found on the peripheral enteric nerves and on the presynaptic ganglia of the parasympathetic system.
      • Izzo A.A.
      • Sharkey K.A.
      Cannabinoids and the gut: new developments and emerging concepts.
      • Storr M.A.
      • Sharkey K.A.
      The endocannabinoid system and gut-brain signalling.
      These receptors mediate the effects of cannabinoids by reducing the release of anterior pituitary hormones (prolactin, gonadotropin, growth hormone) and increasing corticotropin secretions.
      • Wenger T.
      • Moldrich G.
      The role of endocannabinoids in the hypothalamic regulation of visceral function.
      Disturbances of the hypothalamic-pituitary-adrenal axis and the presence of autonomic instability have been described as the framework for symptoms in those with CVS.
      • Taché Y.
      Cyclic vomiting syndrome: the corticotropin-releasing-factor hypothesis.
      Taché
      • Taché Y.
      Cyclic vomiting syndrome: the corticotropin-releasing-factor hypothesis.
      also characterized the increased secretion and activation of corticotropin-releasing factor in the development of CVS. Therefore, we propose that the central effects of long-term cannabis use on the hypothalamic-pituitary-adrenal axis might play a major role in the development of CH. CB1 receptors located in the preoptic area have also been reported to be involved in the hypothermic effects of cannabinoids.
      • Hayakawa K.
      • Mishima K.
      • Nozako M.
      • et al.
      Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.
      • Sim-Selley L.J.
      Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids.
      The impairment of the physiologic thermoregulation provoked by cannabis use might account for the relief of symptoms with compulsive hot bathing that is seen in most patients with CH. Experimental studies, likely involving murine models, would be necessary to confirm these hypotheses. The peripheral CB1 receptors of the enteric nerves have also been implicated in slowing gastrointestinal transit.
      • Izzo A.A.
      • Sharkey K.A.
      Cannabinoids and the gut: new developments and emerging concepts.
      Previously, it was suggested that decreased gastric emptying induced by cannabis use might be responsible for the recurrent emesis seen with CH. However, the majority of our patients had either normal or increased gastric transit. Also, the patients did not have features suggestive of delayed gastric emptying, such as early satiety, bloating, or postprandial predominance of symptoms.
      • Hasler W.L.
      Gastroparesis: symptoms, evaluation, and treatment.
      This case series was performed at a single tertiary care center, which might limit the generalizability of our findings; however, 66% of our patients were from out-of-state, with 28 states and 1 other country (Canada) being represented. In addition, because of the nature of being a tertiary care center, long-term follow-up was considerably limited. Follow-up was available in only 10 patients (10%). Of those 10, 7 (70%) stopped using cannabis and 6 of these 7 (86%) noted complete resolution of their symptoms. The only patient who did not notice any improvement stopped consuming marijuana for only 1 month. The half-life of cannabinoids varies greatly, with a long terminal elimination time, especially in long-term daily consumers.
      • Lowe R.H.
      • Abraham T.T.
      • Darwin W.D.
      • Herning R.
      • Cadet J.L.
      • Huestis M.A.
      Extended urinary Delta9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure.
      Therefore, prolonged abstinence should be recommended.
      Given the retrospective nature of our study, patient recall bias may exist, and some clinical details were not available for all patients, including potential predisposing factors. The majority of marijuana users do not develop this syndrome, and further studies are needed to identify risk factors. The major strength of our study, however, is the large number of cases, representing the largest case series of CH to date.

      Conclusion

      Cannabinoid hyperemesis should be considered in younger patients with long-term cannabis use and recurrent nausea, vomiting, and abdominal pain. The timing, location, and characteristics of symptoms can be helpful in determining the diagnosis of CH, and patients should be asked about the relief of symptoms with hot water bathing. Cessation of cannabis use should result in improvement of clinical symptoms. Studies with higher rates of follow-up are needed, and validation of the proposed diagnostic criteria is required.

      Acknowledgments

      We thank Donna K. Lawson, LPN, (Mayo Clinic, Rochester, MN) for assistance with data collection and Felicity T. Enders, PhD, (Mayo Clinic, Rochester, MN) for assistance with data analysis.

      Supplemental Online Material

      References

        • Leggett T.
        • United Nations Office on Drugs and Crime
        A review of the world cannabis situation.
        Bull Narc. 2006; 58: 1-155
        • Degenhardt L.
        • Chiu W.T.
        • Sampson N.
        • et al.
        Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys.
        PLoS Med. 2008; 5: e141
        • Allen J.H.
        • de Moore G.M.
        • Heddle R.
        • Twartz J.C.
        Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse.
        Gut. 2004; 53: 1566-1570
        • Chang Y.H.
        • Windish D.M.
        Cannabinoid hyperemesis relieved by compulsive bathing.
        Mayo Clin Proc. 2009; 84: 76-78
        • Chepyala P.
        • Olden K.W.
        Cyclic vomiting and compulsive bathing with chronic cannabis abuse.
        Clin Gastroenterol Hepatol. 2008; 6: 710-712
        • Donnino M.W.
        • Cocchi M.N.
        • Miller J.
        • Fisher J.
        Cannabinoid hyperemesis: a case series.
        J Emerg Med. 2011; 40: e63-e66
        • Sontineni S.P.
        • Chaudhary S.
        • Sontineni V.
        • Lanspa S.J.
        Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse.
        World J Gastroenterol. 2009; 15: 1264-1266
        • Soriano-Co M.
        • Batke M.
        • Cappell M.S.
        The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States.
        Dig Dis Sci. 2010; 55: 3113-3119
        • Wallace D.
        • Martin A.L.
        • Park B.
        Cannabinoid hyperemesis: marijuana puts patients in hot water.
        Australas Psychiatry. 2007; 15: 156-158
        • Watts M.
        Cannabinoid hyperemesis presenting to a New Zealand hospital.
        N Z Med J. 2009; 122: 116-118
        • Catto-Smith A.G.
        • Ranuh R.
        Abdominal migraine and cyclical vomiting.
        Semin Pediatr Surg. 2003; 12: 254-258
        • Li B.U.
        • Fleisher D.R.
        Cyclic vomiting syndrome: features to be explained by a pathophysiologic model.
        Dig Dis Sci. 1999; 44: 13S-18S
        • Degenhardt L.
        • Chiu W.T.
        • Sampson N.
        • Kessler R.C.
        • Anthony J.C.
        Epidemiological patterns of extra-medical drug use in the United States: evidence from the National Comorbidity Survey Replication, 2001-2003.
        Drug Alcohol Depend. 2007; 90: 210-223
        • Fleisher D.R.
        • Matar M.
        The cyclic vomiting syndrome: a report of 71 cases and literature review.
        J Pediatr Gastroenterol Nutr. 1993; 17: 361-369
        • Walsh D.
        • Nelson K.A.
        • Mahmoud F.A.
        Established and potential therapeutic applications of cannabinoids in oncology.
        Support Care Cancer. 2003; 11: 137-143
        • Croxford J.L.
        Therapeutic potential of cannabinoids in CNS disease.
        CNS Drugs. 2003; 17: 179-202
        • González S.
        • Cebeira M.
        • Fernández-Ruiz J.
        Cannabinoid tolerance and dependence: a review of studies in laboratory animals.
        Pharmacol Biochem Behav. 2005; 81: 300-318
        • Izzo A.A.
        • Sharkey K.A.
        Cannabinoids and the gut: new developments and emerging concepts.
        Pharmacol Ther. 2010; 126: 21-38
        • Storr M.A.
        • Sharkey K.A.
        The endocannabinoid system and gut-brain signalling.
        Curr Opin Pharmacol. 2007; 7: 575-582
        • Wenger T.
        • Moldrich G.
        The role of endocannabinoids in the hypothalamic regulation of visceral function.
        Prostaglandins Leukot Essent Fatty Acids. 2002; 66: 301-307
        • Taché Y.
        Cyclic vomiting syndrome: the corticotropin-releasing-factor hypothesis.
        Dig Dis Sci. 1999; 44: 79S-86S
        • Hayakawa K.
        • Mishima K.
        • Nozako M.
        • et al.
        Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.
        Life Sci. 2007; 80: 1466-1471
        • Sim-Selley L.J.
        Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids.
        Crit Rev Neurobiol. 2003; 15: 91-119
        • Hasler W.L.
        Gastroparesis: symptoms, evaluation, and treatment.
        Gastroenterol Clin North Am. 2007; 36 (ix): 619-647
        • Lowe R.H.
        • Abraham T.T.
        • Darwin W.D.
        • Herning R.
        • Cadet J.L.
        • Huestis M.A.
        Extended urinary Delta9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure.
        Drug Alcohol Depend. 2009; 105: 24-32

      Linked Article

      • Cannabinoid and Hyperemesis
        Mayo Clinic ProceedingsVol. 87Issue 5
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          We read with interest the article by Simonetto et al1 on cannabinoid hyperemesis (CH) that was published in the February 2012 issue of Mayo Clinic Proceedings. Indeed, this entity is underdiagnosed due to a lack of awareness. Marijuana users presenting to the emergency department with nausea, vomiting, and abdominal pain are a common occurrence; these patients typically undergo several futile investigations and present repeatedly to the hospital with similar symptoms. Many of them are branded as ”drug seekers,” especially since they might have a history of using other recreational drugs along with marijuana.
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