Cannabis Hyperemesis. Constance LeBlanc, MD Professor, Department of Emergency Medicine Associate Dean, Continuing Professional Development

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1 Cannabis Hyperemesis Constance LeBlanc, MD Professor, Department of Emergency Medicine Associate Dean, Continuing Professional Development

2 Disclosures Dalhousie Faculty Member Associate Dean for CPD Emergency Physician Support from NSHA, Health Canada, WCB, CPSNS No support from industry

3 After today you will Use best-evidence to diagnose CHS Have an approach to CHS management Consider prevention

to the US for recreational use after the Mexican-American War The use

4 History The Mexican slang term marihuana was used in the 19th century to highlight its exotic quality A jab at the Mexicans who brought it to the US for recreational use after the Mexican-American War The use of marihuana rose in popularity in the early 1900s, morphing into marijuana

30 25 Prevalence of Self-Reported Cannabis Use 20 15 10 Youth (15-24) General Population

5 30 25 Prevalence of Self-Reported Cannabis Use Youth (15-24) General Population (15+ Adults (25+) Source: CADMUS , CTADS 2015

7 Daily Use 33% of Canadians >15 who used cannabis in the past three months in 2015, use almost daily reported that they used this drug daily 1 183,000,000 (3.8%) of the global population 2 For 10 years THC potency has been increasing 3 1- Statistics Canada. (2017). Canadian Tobacco, Alcohol and Drugs Survey: Summary of results for Ottawa, Ont.: Author. Retrieved April 28, 2017, from summary.html?=undefined&wbdisable=true. 2-Khattar, Neera, and Joanne C. Routsolias. "Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review." American journal of therapeutics(2017). 3- ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades ( ): analysis of current data in the United States. Biol Psychi- atry.2016;79:

8 The Syndrome Syndrome of cyclic vomiting Associated with chronic cannabis use 4 CHS is becoming a commonplace and costly occurrence in hospitals nationwide 2 2- Khattar, Neera, and Joanne C. Routsolias. "Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review." American journal of therapeutics(2017). 4- Rowley E, Benson D, Tiffee A, et al. Clinical and financial implications of emergency department visits for syn- thetic marijuana. Am J Emerg Med. 2017;23:S0735 S6757.

9 Situation Most data from case reports and case series Pathophysiology of the syndrome is unclear Occurrence in some users, but not others, is not understood

10 Literature Literature search was conducted: PubMed, Embase, and Google Scholar until 2017 Publications describing the epidemiology, pathophysiology, diagnostic criteria, and treatments National surveys were also used for current information about this patient population

11 Diagnosis 11 Essential for diagnosis Long term cannabis use Major features 1) Severe cyclic nausea and vomiting. 2) Resolution with cannabis cessation. 3) Relief of symptoms with hot showers or baths. 4) Abdominal pain, epigastric or periumbilical. 5) Weekly use of marijuana Supportive features 1) Age less than 50 years old. 2) Weight loss of > 5kg. 3) Morning predominance of symptoms. 4) Normal bowel habits. 5) Negative laboratory, radiographic and endoscopic test results 11- Simonetto DA, Oxentenko AS, Herman ML, Szostek JH. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc. 2012;87(2): doi: /j.mayocp

12 Diagnosis CHS in the differential diagnosis of patients with regular and chronic cannabis use and 5 intractable nausea and vomiting cyclical vomiting relief of symptoms with hot baths, and resolution of symptoms after cannabis cessation 5- Andrews KH, Bracero LA. Cannabinoid hyperemesis syndrome during pregnancy: a case report. J Reprod Med. 2014;60:

13 Sensitive Characteristics 6 At least weekly cannabis use, more than 1 year (74.8%) Severe nausea/vomiting (100%) Cyclic vomiting that recurs over months (100%) Resolution of symptoms after stopping cannabis (96.8%) Compulsive hot baths/showers with symptom relief (92.3%) Abdominal pain (85.1%) 6- Sorenson CJ, DeSanto K, Borgelt L, et al. Cannabinoid hyperemesis syndrome: diagnosis, pathophysiology, and treatment a systematic review. J Med Toxicol. 2017;13:

14 CH1 receptors are located in the CNS the dorsal ganglia hypothalamus hippocampus cerebellum peripheral enteric nerves presynaptic ganglia of the parasympathetic system

15 Pathophysiology THC acts on cannabinoid receptor CB1 and CB2 receptors CHS is a withdrawal-type syndrome, as a result of long-standing agonism 7 chronic agonism of CB1 receptors produces a paradoxical emetic response in certain patients 8 7- Desai RI, Thakur GA, Vemuri VK, et al. Analysis of tol- erance and behavioral/physical dependence during chronic CB1 agonist treatment: effects of CB1 agonists, antagonists, and noncannabinoid drugs. J Pharmacol Exp Ther. 2013;344: WallaceEA,AndrewsSE,GarmanyCL,etal.Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South Med J. 2011; 104:

16 Pathophysiology THC shown to affect CB1 receptors altering gastrointestinal motility and delaying gastric emptying 9,10 Higher potency of the drug contributing to increased dependence and higher risk of sequela 3 9-Chang YH, Windish DM. Cannabinoid hyperemesis relieved by compulsive bathing. Mayo Clin Proc. 2009; 84: McCallum RW, Soykan I, Sridhar KR, et al. Delta-9-tet- rahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study. Ali- ment Pharmacol Ther. 1999;13: ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades ( ): analysis of current data in the United States. Biol Psychi- atry.2016;79:

17 Treatment Hot Showers and Baths Antiemetics Haloperidol Capsaicin Benzodiazepines Other

18 Antiemetics 8 Ondansetron Promethazine Prochlorperazine Metoclopramide 8- WallaceEA,AndrewsSE,GarmanyCL,etal.Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South Med J. 2011; 104:

19 Haloperidol: Case Reports Inayat et al.: male 25, symptoms refractory to fluids, ondansetron and lorazepam; after haloperidol, GI symptoms subsided 11 Witsil s case report shows patients symptom resolution in 2 hours, discharged in 8 hours 12,13 Mechanism antiemetic efficacy is still unclear: antagonism at D2 dopamine receptors in the CNS 14, Inayat F, Virk HU, Ullah W, et al. Is haloperidol the wonder drug for cannabinoid hyperemesis syndrome? BMJ Case Rep. 2017; Witsil JC, Mycyk MB. Haloperidol, a novel treatment for cannabinoid hyperemesis syndrome. Am J Ther. 2017;24: e64 e Jones JL, Abernathy KE. Successful treatment of suspected cannabinoid hyperemesis syndrome using haloperidol in the outpatient setting. Case Rep Psychiatry. 2016;2016: Hickey JL, Witsil JC, Mycyk MB. Haloperidol for treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med. 2013;31:1003.e Gan TJ, Diemunsch P, Habib A, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014;118:

20 Capsaicin 16 : Case Series Lapoint et al.: 5 patients with complete symptom resolution after topical capsaici to the abdomen 17 Dezieck et al.: 13 patients experienced symptom relief after failure of other treatments Capsaicin acts via hyperstimulation and desensitization of the cannabinoid transient receptor potential vanilloid receptor TRPV1, a modulator of various pain stimuli, activated by extremes of temperature. Agonists cause desensitization, neuronal ablation, and alleviation of pain Accessed March Lapoint J. Case series of patients treated for cannabinoid hyperemesis syndrome with capsaicin cream. Clin Toxi- col (Phila). 2017;52: Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clin Toxicol (Phila). 2017;55: Gavva NR, Bannon AW, Surapaneni S, et al. The vanil- loid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci. 2007;27:

21 Benzodiazepine: Case Reports Cox et al.: patient received 1 mg lorazepam IV after developing extreme anxiety, led to improvement in symptoms, transition to oral intake, discharged with lorazepam tablets; time to discharge was notably longer 20 Baron et al.: patient unable to abstain from marijuana use and continued to present with emesis and renal failure, despite oral benzodiazepines Cox B, Chhabra A, Adler M, et al. Cannabinoid hyper- emesis syndrome: case report of a paradoxical reaction with heavy marijuana use. Case Rep Med. 2012;2012: Baron M, Haymann JP, Wolfromm A, et al. The case: the smoker and the nephrologist. Kidney Int. 2011;79:1385.

22 Other Propranolol Opioids

23 Hot Water Theories Hot water is disrupting the hypothalamic thermoregulatory system counteracting THCs effect on the hypothalamus 9 Hot water causes histamine release and vasodilation counteracting the redistributory effects of THC redistributing blood flow from the gut 11,12 9-Chang YH, Windish DM. Cannabinoid hyperemesis relieved by compulsive bathing. Mayo Clin Proc. 2009; 84: Mahmad A, Jehangir W, Littlefield JM, et al. Cannabis hyperemesis syndrome: a case report review of treat- ment. Toxicol Rep. 2015;2: Patterson DA, Smith E, Monahan M, et al. Cannabinoid hyperemesis and compulsive bathing: a case series and paradoxical pathophysiological explanation. J Am Board Fam Med. 2010;23:

24 Treatment Options A variety of treatment options have also been examined, including hot water baths, haloperidol, capsaicin, and benzodiazepines

25 Take Home Diagnose it cannabis use, vomiting, hot water Treat it with supportive, haloperidol, capsaicin, benzodiazepines

26 Conclusions CHS is increasingly prevalent and complicated problem for health care providers and patients Research must be done to address the diagnostic and therapeutic challenges of this syndrome

27 Conclusions CHS should be treated as any other substance abuse problem Early recognition, symptomatic management, and a support system to help end the addiction

28 References 1. Statistics Canada. (2017). Canadian Tobacco, Alcohol and Drugs Survey: Summary of results for Ottawa, Ont.: Author. Retrieved April 28, 2017, from canada/services/canadian-tobacco-alcohol-drugs-survey/2015- summary.html?=undefined&wbdisable=true. 2. Khattar, Neera, and Joanne C. Routsolias. "Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review." American journal of therapeutics(2017). 3. ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades ( ): analysis of current data in the United States. Biol Psychi- atry.2016;79: Rowley E, Benson D, Tiffee A, et al. Clinical and financial implications of emergency department visits for syn- thetic marijuana. Am J Emerg Med. 2017;23:S0735 S Andrews KH, Bracero LA. Cannabinoid hyperemesis syndrome during pregnancy: a case report. J Reprod Med. 2014;60: Sorenson CJ, DeSanto K, Borgelt L, et al. Cannabinoid hyperemesis syndrome: diagnosis, pathophysiology, and treatment a systematic review. J Med Toxicol. 2017;13: Desai RI, Thakur GA, Vemuri VK, et al. Analysis of tol- erance and behavioral/physical dependence during chronic CB1 agonist treatment: effects of CB1 agonists, antagonists, and noncannabinoid drugs. J Pharmacol Exp Ther. 2013;344: WallaceEA,AndrewsSE,GarmanyCL,etal.Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South Med J. 2011; 104: Chang YH, Windish DM. Cannabinoid hyperemesis relieved by compulsive bathing. Mayo Clin Proc. 2009; 84:76 78.

29 10. McCallum RW, Soykan I, Sridhar KR, et al. Delta-9-tet- rahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study. Ali- ment Pharmacol Ther. 1999;13: Simonetto DA, Oxentenko AS, Herman ML, Szostek JH. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc. 2012;87(2): doi: /j.mayocp Inayat F, Virk HU, Ullah W, et al. Is haloperidol the wonder drug for cannabinoid hyperemesis syndrome? BMJ Case Rep. 2017; Witsil JC, Mycyk MB. Haloperidol, a novel treatment for cannabinoid hyperemesis syndrome. Am J Ther. 2017;24: e64 e Jones JL, Abernathy KE. Successful treatment of suspected cannabinoid hyperemesis syndrome using haloperidol in the outpatient setting. Case Rep Psychiatry. 2016;2016: Hickey JL, Witsil JC, Mycyk MB. Haloperidol for treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med. 2013;31:1003.e Gan TJ, Diemunsch P, Habib A, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014;118: Accessed March Lapoint J. Case series of patients treated for cannabinoid hyperemesis syndrome with capsaicin cream. Clin Toxi- col (Phila). 2017;52: Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clin Toxicol (Phila). 2017;55: Gavva NR, Bannon AW, Surapaneni S, et al. The vanil- loid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J Neurosci. 2007;27: Cox B, Chhabra A, Adler M, et al. Cannabinoid hyper- emesis syndrome: case report of a paradoxical reaction with heavy marijuana use. Case Rep Med. 2012;2012:

30 Baron M, Haymann JP, Wolfromm A, et al. The case: the smoker and the nephrologist. Kidney Int. 2011;79: Nogi, Masayuki, David Fergusson, and John Michael Chua Chiaco. "Mid-ventricular variant takotsubo cardiomyopathy associated with cannabinoid hyperemesis syndrome: a case report." Hawai'i Journal of Medicine & Public Health 73.4 (2014): Jin KL, Mao XO, Goldsmith PC, Greenberg DA. CB1 cannabinoid receptor induction in experimental stroke. Ann Neurol. 2000;48(2): Taché Y. Cyclic vomiting syndrome: the corticotropin-releasing-factor hypothesis. Dig Dis Sci. 1999;44(8 Suppl):79S 86S. 24. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation. 2008;118(4): doi: /CIRCULATIONAHA Izzo AA, Sharkey KA. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther. 2010;126(1): doi: /j.pharmthera Niederhoffer N, Szabo B. Effect of the cannabinoid receptor agonist WIN on sympathetic cardiovascular regulation. Br J Pharmacol. 1999;126(2): doi: /sj.bjp Allen JH. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut. 2004;53(11): doi: /gut Hawaii J Med Public Health Apr; 73(4):

CYCLICAL VOMITING ENSHROUDED IN A CLOUD

CYCLICAL VOMITING ENSHROUDED IN A CLOUD HPI Ø39 year old man ØEpigastric pain X 3 days Recurrent for the past 2 years (@least 2x/month) Dull then sharp, 8/10 Non radiating,constant ØAssociated with nausea