Capsaicin Cream for Treatment of CannabinoidJessica Graham, MD,a Michael Barberio, HyperemesisPharmD,b George Sam Wang, MDa Syndrome
in Adolescents: A Case Seriesabstract Cannabinoid hyperemesis syndrome (CHS) is an underrecognized diagnosis among adolescents. In the adult literature, it is characterized as nausea, vomiting, and abdominal pain in patients with chronic marijuana use. CHS is often refractory to the standard treatment of nausea and vomiting. Unconventional antiemetics, such as haloperidol, have been successful in alleviating symptoms; however, even 1 dose of haloperidol can lead to
grave adverse effects, such as dystonia, extrapyramidal reactions, and aSection of Emergency Medicine, Department of Pediatrics, neuroleptic malignant syndrome. The use of topical capsaicin cream to University of Colorado Anschutz Medical Campus, and bDepartment of Pharmacy, Children’s Hospital Colorado, treat CHS has been well described in the adult literature. This treatment Aurora, Colorado is cost-effective and is associated with few serious side effects. Here, we describe 2 adolescent patients with nausea, vomiting, and abdominal pain Dr Graham drafted the initial manuscript; Drs Graham, Barberio, and Wang reviewed and revised in the setting of chronic cannabis use whose symptoms were not relieved by the manuscript; and all authors approved the final standard antiemetic therapies, but who responded well to topical capsaicin manuscript as submitted. ’ administration in our pediatric emergency department. We also discuss the DOI: https://doi.org/10.1542/peds.2016-3795 pathophysiology behind capsaicin s efficacy. These are the first reported Accepted for publication Mar 13, 2017 cases in which capsaicin was successfully used to treat CHS in pediatric Address correspondence to Jessica Graham, patients. MD, Pediatric Emergency Medicine, University of Colorado at Denver–Anschutz Medical Campus, 13123 E 16th Ave, B251, Aurora, CO 80045. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, Cannabinoid hyperemesis syndrome department (ED) with 1 week of 1098-4275). (CHS) is a clinical diagnosis– that nausea, vomiting, and abdominal pain. Copyright © 2017 by the American Academy of has been described in patients1 5 who She reported chronic intermittent Pediatrics use cannabis chronically. It is epigastric pain that had significantly FINANCIAL DISCLOSURE: Dr Wang received a characterized by significant nausea, worsened over the previous week grant from the Colorado Department of Public abdominal– pain, and cyclic vomiting, and was now associated with nausea Health and Environment on the evaluation of the pharmacokinetics of cannabidiol in pediatric which are4 14 often relieved by hot and vomiting. She denied fever, bathing. Most patients receive diarrhea, dysuria, or hematuria. Her epilepsy patients. He also receives royalties from significant medical evaluation without last menstrual period was 1 week UpToDate for authorship contributions for related – topics. Drs Graham and Barberio have indicated significant findings and are refractory1,3 7 before and she denied recent sexual they have no financial relationships relevant to this to standard medical therapies. activity. She denied ethanol use but ° article to disclose. We present 2 adolescent patients did admit to cannabis use. Vital signs FUNDING: No external funding. with delayed diagnosis of CHS whose were a temperature of 36.8 C, blood POTENTIAL CONFLICT OF INTEREST: The authors symptoms improved with application pressure (BP) of 106/63 mm Hg, heart have indicated they have no potential conflicts of of capsaicin cream. rate (HR) of 103 beats per minute, interest to disclose. Case Presentations respiratory rate (RR) of 16 breaths per minute, and pulse oxygen saturation o To cite: Graham J, Barberio M, Wang GS. Cap Case 1 (Sp 2) of 99%. She complained of saicin Cream for Treatment of Cannabinoid Hyper diffuse abdominal pain, but had a soft emesis Syndrome in Adolescents: A Case Series. abdomen without peritoneal signs. Pediatrics. 2017;140(6):e20163795 A previously healthy 16-year-old girl Laboratory testing, including a basic presented to an outside emergency metabolic panel, complete blood count, Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 6, December 2017:e20163795 Case Report
Graham et al 2017 ROUGH GALLEY PROOF Capsaicin Cream for Treatment of https://doi.org/10.1542/peds.2016-3795 December 2017 Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series 6 140 Pediatrics lipase, liver function tests, urinalysis, points and her nausea resolved. peritoneal signs. Laboratory testing, “ ” and a urine pregnancy test were The patient did report the side including a basic metabolic panel, significant only for a potassium level effect of a mild burning sensation complete blood count, liver function of 3.2 mmol/L, bicarbonate of 28 on her abdomen where the cream tests, and lipase, was significant mmol/L, and a urinalysis revealing had been applied but was overall only for bilirubin of 1.4 mg/dL. 40 mg/dL ketones, trace blood, and satisfied by the symptom relief. She An ultrasound of the abdomen 30 mg/dL protein. She received had improvement in abdominal was normal. Negative workup, 4 mg intravenous ondansetron, tenderness on examination and was chronic cannabis use, and symptom 10 mg metoclopramide, a 1000-mL Casedischarged 2 from the hospital. improvement with hot showers led normal saline bolus, and 30 mL of an to a presumed diagnosis of CHS. oral lidocaine/diphenhydramine/ The patient verbally agreed to try aluminum and magnesium hydroxide capsaicin cream for the treatment A 20-year-old man with moderate solution. She left against medical of CHS. Capsaicin cream, 0.025% persistent asthma was seen in advice before undergoing a computed (1-mm-thick coating), was applied our ED with abdominal pain and tomographic scan despite expressing to his abdomen. Thirty minutes after vomiting. He admitted to being that there was no improvement in application, the patient reported acutely intoxicated with marijuana. her symptoms. ° marked improvement in abdominal His vital signs were a temperature pain and nausea. He also complained of 36.8 C, BP of 139/85 mm Hg, The next evening, the patient of a burning sensation over his HR of 139 beats per minute, RR of presented to our institution with o abdomen but was satisfied with the 16 breaths per minute, and Sp 2 of continued abdominal pain, nausea, symptom relief and was discharged. 95%. Examination was significant and emesis. A detailed history for epigastric tenderness, but Discussion revealed chronic cannabis use, he had a soft abdomen and no which increased over the last week peritoneal signs. He was given in attempts to treat her nausea and 4 mg oral ondansetron and 15 mL CHS was first described in 2004 abdominal pain (multiple times of an oral aluminum/magnesium in a case series of 9 patients who per day). She could not identify hydroxide/diphenhydramine/ used cannabis chronically and alleviating or worsening factors. ° lidocaine/simethicone solution. He who exhibited cyclic vomiting and Her vital signs were a temperature 1 subsequently tolerated oral fluids compulsive bathing with hot water. of 36.6 C, HR of 80 beats per and was sent home with ondansetron There have been several case series minute, BP of 113/74 mm Hg, RR o and ranitidine for presumed gastritis. and reports describing patients with of 16 breaths per minute, and Sp 2 – chronic marijuana use and similar of 97%. Her pain was 6 out of 10 One week later, he returned 4,6, 8 15 associated symptoms. possible points. On examination, complaining of persistent abdominal Although CHS has mainly been she exhibited voluntary guarding pain and vomiting. Since his initial described in adult patients, health with tenderness in her left upper visit, he had been taking ranitidine care providers should also be aware quadrant and epigastric region; her twice daily and ondansetron nearly that this diagnosis can occur in abdomen was soft and nondistended daily, but suffered from worsening 7,16 adolescents. In 1 published case, without peritoneal signs. She was pain. He reported that his pain was a 17-year-old presented to the ED given 4 mg sublingual ondansetron migratory, traveling from his right 5 times for abdominal pain, nausea, and 5 mg oral oxycodone without lower to right upper to left upper and vomiting over the course of improvement in her nausea or quadrant to his epigastric region. 7 1 year. He received an extensive abdominal pain. Due to a history of He had 3 additional episodes of medical workup, which was negative. cannabis use, the refractory nature nonbloody emesis since his last Consistent with CHS, his symptoms of abdominal pain, and an otherwise visit. He endorsed at least twice- were relieved by hot showers and negative diagnostic workup, CHS daily marijuana use for >1 year and only completely resolved after the became the working diagnosis. that his abdominal pain improved cessation of marijuana use. After the risks and benefits were with hot showers. He denied fever, discussed, she verbally agreed to try diarrhea, dysuria, or hematuria. The pathophysiology of CHS is not ° capsaicin cream for the treatment Vital signs were a temperature of well understood at this time. In of CHS. Capsaicin cream, 0.025% 36.3 C, BP of 125/73 mm Hg, HR some circumstances, cannabis has (1-mm-thick coating), was applied of 73 beats per minute, RR of 12 antiemetic effects; therefore, the o2 ’ to her abdomen. Thirty minutes breaths per minute, and Sp of 96%. concept of it causing3,17, 18 hyperemesis is after capsaicin was applied, her pain Abdominal examination revealed a counterintuitive. Marijuana s decreased to a 3 out of 10 possible soft, nondistended abdomen without effects on the nausea and vomiting Downloaded from www.aappublications.org/news by guest on September 26, 2021 2 Graham et al
Graham et al 2017 ROUGH GALLEY PROOF Capsaicin Cream for Treatment of https://doi.org/10.1542/peds.2016-3795 December 2017 Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series 6 140 Pediatrics centers have been hypothesized to the treatment of CHS with application be considered as a cost-effective occur via CB1 and CB2 receptors of 0.075% capsaicin to the abdomen treatment and diagnostic option.
in the preoptic dorsal ganglia, and 0.025% capsaicin26, to27 the back, Abbreviations hypothalamus, hippocampus, arms, and abdomen. cerebellum, and peripheral enteric – Currently, there are no laboratory or nerves of the parasympathetic 3,17 19 radiographic tests that are diagnostic BP: blood pressure system. These receptors for CHS. Studies are used to rule out CB: cannabinoid are linked to the hypothalamic- common abdominal pain diagnoses. CHS: cannabinoid hyperemesis pituitary-adrenal axis and are Both histories and symptoms were syndrome thought to mediate the release consistent with CHS, and capsaicin ED: emergency department of prolactin, gonadotropin, and cream provided symptomatic relief HR: heart rate growth hormone (anterior pituitary where conventional antiemetics RR: respiratory rate hormones) and corticotropin. o2 and medical treatment had failed. Sp : pulse oxygen saturation The proposed mechanism of Other treatment modalities for CHS TRPV1: transient receptor cyclic vomiting syndrome, a have included intravenous fluids, potential vanilloid-1 gastrointestinal condition with 28 antiemetics, and haloperidol. The receptor symptoms comparable to CHS, is a “ ” only adverse effect our patients disturbance of the hypothalamic- 13,20 described was a burning sensation pituitary-adrenal axis. It has been References on their skin. Our patients did not proposed that CHS may function 1. Allen JH, de Moore GM, Heddle R, return to our ED after treatment by a similar mechanism, acting on Twartz JC. Cannabinoid hyperemesis: with capsaicin cream. By effectively cannabinoid (CB) receptors linked to cyclical hyperemesis in association alleviating symptoms in our the axis. with chronic cannabis abuse. Gut. patients, we prevented further 2004;53(11):1566–1570 unnecessary medical workup as The interesting, almost 2. Andrews KH, Bracero LA. Cannabinoid well as unnecessary treatment with pathognomonic, characteristic of hyperemesis syndrome during high-risk medications, including CHS is the relief of symptoms by hot pregnancy: a case report. J Reprod opioid analgesics. Our case report is showering or bathing. This effect was Med. 2015;60(9–10):430–432 limited by describing only 2 clinical initially proposed to be motivated cases involving patients seen in our 3. Lu ML, Agito MD. Cannabinoid by impaired thermoregulation hyperemesis syndrome: marijuana is pediatric ED. Thus, the effectiveness mediated by the stimulation of CB both antiemetic and proemetic. Cleve 13 of capsaicin may not be universal receptors in the preoptic area. Clin J Med. 2015;82(7):429–434 for all patients with CHS. Although However, the receptor that may the preferred long-term treatment 4. Parekh JD, Wozniak SE, Khan K, actually deserve credit for this would be cessation of cannabis use, Dutta SK. Cannabinoid hyperemesis phenomenon in CHS is the transient syndrome. BMJ Case Rep. acute treatment with capsaicin is receptor potential vanilloid-1 2016;bcr2015213620 inexpensive, with few reported side receptor (TRPV1), a nociceptor effects. 5. Sorenson CJ, Desanto K, Borgelt L, found in the peripheral nervous Phillips KT, Monte AA. Cannabinoid system that is involved in the pain Recent estimates indicate that hyperemesis syndrome: diagnosis, relief we feel from endocannabinoid 7.4% of all adolescents29 are current pathophysiology, and treatment—a stimulation and which21 also users of marjiuana. In Colorado, systematic review. J Med Toxicol. regulates body heat. TRPV1 is where both retail and recreational 2017;13(1):71 87 ° – – activated by exposure22 24 to scalding marijuana is now legal, the number 6. Chang YH, Windish DM. Cannabinoid heat (109 F). Interestingly, of patients presenting to the ED for hyperemesis relieved by capsaicin24 also stimulates25 the TRPV1 cyclic vomiting nearly doubled after30 compulsive bathing. Mayo Clin Proc. receptor. Lapoint identified the liberalization of medical marijuana. 2009;84(1):76–78 clinical advantage of the physiologic As marijuana becomes more publicly 7. Desjardins N, Stheneur C. Cannabinoid link between cannabis, heat, and available, health care providers, hyperemesis syndrome: a review of capsaicin when they applied the chili including pediatricians, need to the literature [in French]. Arch Pediatr. pepper derivative (0.075% capsaicin) be vigilant about potential health 2016;23(6):619–623 to the abdomens of several adult effects, including the symptoms 8. Habboushe J, Sedor J. Cannabinoid patients with CHS and observed of CHS. Although more research is hyperemesis acute renal failure: relief of their nausea, vomiting, and needed on the potential benefits of a common sequela of cannabinoid abdominal pain. Additional case capsaicin cream and the use for CHS, reports subsequently also described application of capsaicin cream should Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 6, December 2017 3
Graham et al 2017 ROUGH GALLEY PROOF Capsaicin Cream for Treatment of https://doi.org/10.1542/peds.2016-3795 December 2017 Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series 6 140 Pediatrics hyperemesis syndrome. Am J Emerg 18. Söderpalm AH, Schuster A, de Wit Toxicology Annual Scientific Meeting Med. 2014;32(6):690.e1–690.e2 H. Antiemetic efficacy of smoked abstracts. Abstract 51. Available 9. Hopkins CY, Gilchrist BL. A case of marijuana: subjective and behavioral at: www.acmt.net/Abstracts_41-60. cannabinoid hyperemesis syndrome effects on nausea induced by syrup html#fiftyone. Accessed November 11, caused by synthetic cannabinoids. of ipecac. Pharmacol Biochem Behav. 2016 2001;69(3 4):343 350 J Emerg Med. 2013;45(4):544–546 – – 26. Biary R, Oh A, Lapoint J, Nelson LS, 10. Iacopetti CL, Packer CD. Cannabinoid 19. Patterson DA, Smith E, Monahan M, Hoffman RS, Howland MA. Topical hyperemesis syndrome: a case report et al. Cannabinoid hyperemesis and capsaicin cream used as a therapy for and review of pathophysiology. Clin compulsive bathing: a case series cannabinoid hyperemesis syndrome. and paradoxical pathophysiological American College of Medical Med Res. 2014;12(1–2):65–67 explanation. J Am Board Fam Med. Toxicology Annual Scientific Meeting 11. Price SL, Fisher C, Kumar R, Hilgerson 2010;23(6):790–793 Abstracts. Abstract 232. Available A. Cannabinoid hyperemesis syndrome 20. Sunku B. Cyclic vomiting at: https://www.clintox.org/NACCT/ as the underlying cause of intractable syndrome: a disorder of all ages. 2014/NACCTabstracts.pdf. Accessed nausea and vomiting. J Am Osteopath Gastroenterol Hepatol (NY). November 11, 2016 Assoc. 2011;111(3):166–169 2009;5(7):507–515 27. Lapoint J. Case series of patients 12. Sannarangappa V, Tan C. Cannabinoid 21. Ryskamp DA, Redmon S, Jo AO, Kri aj treated for cannabinoid hyperemesis hyperemesis. Intern Med J. ž D. TRPV1 and endocannabinoids: syndrome with capsaicin cream. 2009;39(11):777 778 – emerging molecular signals that American College of Medical 13. Simonetto DA, Oxentenko AS, modulate mammalian vision. Cells. Toxicology Annual Scientific Meeting Herman ML, Szostek JH. Cannabinoid 2014;3(3):914–938 Abstracts. Abstract 53. Available hyperemesis: a case series of at: https://www.clintox.org/NACCT/ 22. Cao E, Cordero-Morales JF, Liu B, 98 patients. Mayo Clin Proc. 2014/NACCTabstracts.pdf. Accessed Qin F, Julius D. TRPV1 channels 2012;87(2):114 119 November 11, 2016 – are intrinsically heat sensitive 14. Sontineni SP, Chaudhary S, Sontineni V, and negatively regulated by 28. Jones JL, Abernathy KE. Successful Lanspa SJ. Cannabinoid hyperemesis phosphoinositide lipids. Neuron. treatment of suspected cannabinoid syndrome: clinical diagnosis of an 2013;77(4):667–679 hyperemesis syndrome using underrecognised manifestation of 23. Schmid SM, Lapaire O, Huang DJ, haloperidol in the outpatient chronic cannabis abuse. World J J rgens FE, G th U. Cannabinoid setting. Case Rep Psychiatry. Gastroenterol. 2009;15(10):1264 1266 ü ü – hyperemesis syndrome: an 2016;2016:3614053 15. Donnino MW, Cocchi MN, Miller J, underreported entity causing nausea 29. Hedden S, Kennet J, Lipari R, Medley Fisher J. Cannabinoid hyperemesis: and vomiting of pregnancy. Arch G, Tice P. Behavioral health trends in a case series. J Emerg Med. Gynecol Obstet. 2011;284(5): the United States: results from the 2011;40(4):e63–e66 1095–1097 2014 National Survey on Drug Use and 16. Miller JB, Walsh M, Patel PA, et al. 24. Wen H, Qin F, Zheng W. Toward Health. SAMHSA Web site. Available at: Pediatric cannabinoid hyperemesis: elucidating the heat activation www.samhsa.gov/data/sites/default/ two cases. Pediatr Emerg Care. mechanism of the TRPV1 files/NSDUH-FRR1-2014/NSDUH-FRR1- 2010;26(12):919–920 channel gating by molecular 2014.pdf. Accessed November 4, 2016 17. Smith LA, Azariah F, Lavender VT, Stoner dynamics simulation. Proteins. 30. Kim HS, Anderson JD, Saghafi O, NS, Bettiol S. Cannabinoids for nausea 2016;84(12):1938–1949 Heard KJ, Monte AA. Cyclic vomiting and vomiting in adults with cancer 25. Lapoint J. Capsaicin cream for presentations following marijuana receiving chemotherapy. Cochrane treatment of cannabinoid hyperemesis liberalization in Colorado. Acad Emerg Database Syst Rev. 2015;11:CD009464 syndrome. American College of Medical Med. 2015;22(6):694–699
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Graham et al 2017 ROUGH GALLEY PROOF Capsaicin Cream for Treatment of https://doi.org/10.1542/peds.2016-3795 December 2017 Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series 6 140 Pediatrics Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series Jessica Graham, Michael Barberio and George Sam Wang Pediatrics 2017;140; DOI: 10.1542/peds.2016-3795 originally published online November 9, 2017;
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Downloaded from www.aappublications.org/news by guest on September 26, 2021 Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series Jessica Graham, Michael Barberio and George Sam Wang Pediatrics 2017;140; DOI: 10.1542/peds.2016-3795 originally published online November 9, 2017;
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