Cannabinoid hyperemesis syndrome

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Cannabinoid hyperemesis syndrome
Girl being in the shower.jpg
People with cannabinoid hyperemesis syndrome often find some relief with hot showers[1]
SpecialtyToxicology
SymptomsNausea, vomiting, stomach pain[2]
ComplicationsKidney failure, electrolyte problems, skin burns from hot water[1]
CausesLong term cannabis use[2]
Diagnostic methodBased on the symptoms[1]
Differential diagnosisCyclical vomiting syndrome[1]
TreatmentStopping cannabis, hot showers[2]
MedicationCapsaicin cream[1]
Frequency2.7 million per year (US)[1]

Cannabinoid hyperemesis syndrome is recurrent nausea, vomiting, and cramping abdominal pain due to cannabis use.[3] These symptoms may improve temporarily by taking a hot shower or bath.[1] Complications may include kidney failure, electrolyte problems, and skin burns from hot water.[1] Deaths due to these complications have occurred.[1]

Weekly cannabis use is generally required for the syndrome to occur.[1] The underlying mechanism is unclear, with several possibilities proposed.[1] Diagnosis is based on the symptoms.[1] The condition is typically present for some time before the diagnosis is made.[1] Another condition that may present similarly is cyclic vomiting syndrome.[1]

Definitive treatment involves stopping use of cannabis.[1] Up to two weeks may be required to see a benefit.[1] Treatments during an episode of vomiting is generally supportive in nature.[1] There is tentative evidence for the use of capsaicin cream on the abdomen during an acute episode.[1]

While the number of people affected is unclear,[4] one estimate puts the number at 2.7 million people in the United States a year.[1] Of those who go to the emergency department in the United States with recurrent vomiting, about 6% have the condition.[1] The syndrome was first described in 2004, and simplified diagnostic criteria published in 2009.[5][6]

Signs and symptoms[edit]

The long-term and short-term effects of cannabis use are associated with behavioral effects leading to a wide variety of effects on the body systems and physiological states.[6] Cannabinoid hyperemesis syndrome is a paradoxical syndrome characterized by hyperemesis (persistent vomiting), as opposed to the better known antiemetic properties of cannabinoids.[7] Specifically, cannabinoid hyperemesis syndrome takes the pattern of cyclical nausea, vomiting, and abdominal pain in the setting of chronic cannabinoid use.[7] The abdominal pain tends to be mild and diffused.[8] There are three phases of cannabinoid hyperemesis syndrome: the prodromal phase, the hyperemetic phase, and the recovery phase.[9]

The prodromal phase is characterized by subsyndromal symptoms of cannabinoid hyperemesis syndrome, including mild discomfort and nausea upon waking. Prior to the use of compensatory exposure to hot water to treat symptoms, people sometimes increase their intake of cannabinoids in an effort to treat the persistent nausea they experience. This phase can last for months or even years.[9]

The hyperemetic phase is characterized by the full syndromal symptoms of cannabinoid hyperemesis syndrome, including persistent nausea, vomiting, abdominal pain, and retching.[9] Retching can occur up to 5 times per hour.[8] It is very difficult to take food or medicine by mouth during this stage, and patients may develop a fear of eating. Weight loss and dehydration due to decreased oral intake and vomiting are possible. Compensatory exposure to hot water, even for hours at a time, may be attempted for symptomatic relief, resulting in compulsive bathing/showering.[9] People have described the hot water relief as "temperature-dependent," meaning that hotter temperatures provide greater relief. It is during this phase that people with cannabinoid hyperemesis syndrome are likely to present to the emergency department of the hospital for treatment.[9]

The recovery phase begins after the patient abstains from cannabinoids, and can last days to months. Lost weight can be regained due to a restoration of normal oral intake, and compulsive bathing/showering can give way to normal patterns of behavior.[9]

Complications[edit]

Individual attacks can lead to complications, such as acute kidney injury.[10] In the setting of cannabinoid hyperemesis syndrome, this may be defined as cannabinoid hyperemesis acute renal failure (CHARF).[10] CHARF occurs through dehydration secondary due to persistent vomiting and hot showers, leading to prerenal azotemia.[10] A case report of acute renal failure, albeit in the setting of rhabdomyolysis, has been reported with the use of synthetic cannabinoids.[11]

Pathogenesis[edit]

Cannabis contains more than 400 different chemicals, of which about 60 are cannabinoids.[7] The pathophysiology of cannabinoid hyperemesis syndrome is complicated by the complex action of these chemicals throughout the body, both in the central nervous system and in the gastrointestinal system.[7]

Various pathogenic mechanistic theories attempting to explain symptoms have been put forward. These theories follow two themes: (1) dose dependent buildup of cannabinoids and related effects of cannabinoid toxicity or (2) the functionality of cannabinoid receptors in the brain and particularly in the hypothalamus (which regulates body temperature and the digestive system).[12][unreliable medical source?] However, the mechanisms by which cannabis causes or controls nausea and the adverse consequences of long-term cannabis toxicity remain unknown and organic disease should not be ruled out as a possible cause.[12][unreliable medical source?]

Cannabinoid buildup theory[edit]

Tetrahydrocannabinol (THC) is a fat-soluble cannabinoid that can be deposited into a person's fat stores, accounting for the long elimination half-life of THC.[8] During periods of stress or food deprivation, a person's fat stores can be mobilized (lipolysis) for energy consumption, releasing the previously stored THC as well.[8] THC can then leach back into the bloodstream, leading to progressively higher concentrations in the blood.[7] The mechanism can be characterized as a "reintoxication effect."[8] Another cannabinoid called cannabigerol acts as an antagonist at cannabinoid 1 (CB1) and serotonin 1A receptors, antagonizing the anti-emetic effects of cannabidiol that occurs through its effects on serotonin.[8]

Hypothalamic theory[edit]

Cannabidiol, a cannabinoid found in cannabis, can increase the expression of the CB1 receptors in the hypothalamus of the brain.[8] Additionally, THC acts at the CB1 receptors to induce a hypothermic effect, lowering body temperature.[8] This might explain how exposure to hot water can relieve symptoms of cannabinoid hyperemesis syndrome, reversing the decrease in the thermoregulatory set point induced by cannabinoids.[7]

Diagnosis[edit]

Various diagnostic frameworks for cannabinoid hyperemesis syndrome have been proposed.[3] As of 2015, the modified criteria by Simonetto et al. are the most frequently used.[7] The most important feature is detecting a history of cannabinoid use, the denial of which can delay proper diagnosis.[9] A urine drug screen can be useful for objectively determining the presence of cannabinoids in a person's system.[9] Cannabinoid metabolites (specifically 11-nor-Δ9-carboxylic acid) can be detected in urine for about 2–8 days with short-term use, and for 14–42 days of chronic use.[13]

Other commonly used diagnostic tests include laboratory blood tests (complete blood count and differential, blood glucose, basic metabolic panel, pancreatic and liver enzymes), pregnancy test, urinalysis, and plain flat radiographic series.[8]

Sontineni criteria[6]
Essential
  • Cannabis use for years
Major
  • Severe nausea and vomiting
  • Vomiting that recurs in a cyclic pattern over months
  • Resolution of symptoms after stopping cannabis use
Supportive
  • Compulsive hot baths with symptom relief
  • Colicky abdominal pain
  • No evidence of gallbladder or pancreatic inflammation
Modified criteria[14]
Essential
  • Long-term cannabis use
Major
  • 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
  • Age less than 50 y
  • Weight loss of >5 kg
  • Morning predominance of symptoms
  • Normal bowel habits
  • Negative laboratory, radiographic, and endoscopic test results
Sorensen et al. 2017 systematic review[3]
Criteria
  • Severe cyclic vomiting usually accompanied by abdominal pain
  • Symptom onset preceded by at least weekly cannabis use
  • Temporary relief of symptoms with hot bathing
  • Resolution of symptoms with cannabis cessation
  • Supportive features: male gender, cannabis use onset in teenage years, symptom onset in the third decade of life

Differential diagnosis[edit]

Cyclic vomiting syndrome versus cannabinoid hyperemesis syndrome[7][8]
Clinical features Cyclic vomiting syndrome Cannabinoid hyperemesis syndrome
Hypothesized cause mtDNA mutations Exogenous cannabinoid ingestion
Trigger (e.g. infection, stress) Frequently Absent
Prodromal phase Common Common
Cannabis use Infrequently Universal
Sex Females > Males Males > Females
Vomiting Universal Universal
Abdominal pain Frequent; moderate-severe Frequent; mild-moderate
Dehydration and increased drinking Frequent Frequent
Weight loss Frequent Frequent
Frequent and compulsive hot showers or baths Absent Universal
Psychiatric disorders Frequent Rare
Migraine headache Frequent Rare
Leukocytosis or neutrophilia Occasionally Occasionally
Low blood potassium Occasionally, due to hyperemesis Occasionally, due to hyperemesis
Gastric emptying study result Accelerated or normal Delayed or normal
Urine cannabinoid screen Typically negative Typically positive
Endoscopy result Normal Frequently esophagitis or gastritis

Prior to diagnosing and treating for a presumed cannabinoid hyperemesis syndrome, more serious medical conditions need to be ruled out.[3] Medical conditions that may present similarly to cannabinoid hyperemesis syndrome include cyclic vomiting syndrome,[8] bowel perforation or obstruction, gastroparesis, cholangitis, pancreatitis, nephrolithiasis, cholecystitis, diverticulitis, ectopic pregnancy, pelvic inflammatory disease, heart attack, acute hepatitis, adrenal insufficiency, and ruptured aortic aneurysm.[3][9] In general, cannabinoid hyperemesis syndrome is most often misdiagnosed as cyclic vomiting syndrome.[8] However, if simple laboratory tests and imaging have excluded more serious conditions, it is reasonable to monitor for a worsening of the patient's status to prevent the unnecessary application of more invasive, and potentially dangerous, diagnostic procedures (e.g. exploratory surgery).[3] A complete history of the person's use of cannabinoids is important in establishing the correct diagnosis.[3]

Cannabinoid hyperemesis syndrome is sometimes left undiagnosed, even for years.[7] This may be due to reluctance on behalf of patients to fully disclose their use of cannabis to healthcare professionals, especially when another person is accompanying the partner to an appointment or emergency department visit.[7] Identifying the correct diagnosis saves money for the healthcare system and reduces morbidity associated with the condition.[8]

Treatment[edit]

Many traditional medications for nausea and vomiting are ineffective. Treatment is otherwise supportive and focuses on stopping cannabis use.[15] With the cessation of cannabinoid use, complete symptomatic relief can take between 7–10 days.[16] Proper patient education includes informing patients that their symptoms are due to their use of cannabis/cannabinoids, and that exposure to cannabinoids in the future are likely to cause their symptoms to return.[16] Clinical pharmacists can play a role in administering this education, as well as encouraging patients to seek the assistance of mental health providers.[9] Abstinence from cannabinoids currently remains the only definitive treatment.[3] Cognitive behavioral therapy and motivational enhancement therapy are evidence-based outpatient treatment options for patients with cannabis use disorder.[8]

Symptomatic relief is noted with exposure to hot water (greater than 41 degrees C), which is mediated by TRPV–the capsaicin receptor.[16] Assessing for dehydration due to vomiting and hot showers is important as it can lead to acute kidney failure, and this is easily treated with IV fluids.[10] If dehydration is severe, hospitalization may be required.[8] Based on the mechanism of the effect, some clinicians have used topical capsaicin cream applied to the periumbilical area in the treatment of acute cannabinoid hyperemesis syndrome.[16] The use of capsaicin as first-line treatment for cannabinoid hyperemesis syndrome has been well-tolerated, though the evidence for efficacy is limited.[16] The use of hot water showers in the emergency department setting has been advocated in situations where topical capsaicin cream is unavailable, though the same precautions to hot water use (dehydration, burn injury) are required.[16]

The use of antipsychotics, such as haloperidol and olanzapine, have provided complete relief of symptoms in case-reports.[16][17] The evidence for the use of benzodiazepines, such as lorazepam,[17] has shown mixed results.[16] Other drug treatments that have been tried, with unclear efficacy, include neurokinin-1 receptor antagonists,[8] first-generation antihistamines (e.g. diphenhydramine), 5-HT3 receptor antagonists (e.g. ondansetron), and non-antipsychotic antidopaminergics (e.g. metoclopramide).[16]

Acetaminophen has shown some benefit in case reports for alleviating headaches associated with cannabinoid hyperemesis syndrome.[9] Opioids can provide some relief of abdominal pain, but their use is discouraged due to the risk of worsening nausea and vomiting.[8]

Prognosis[edit]

Acute episodes of cannabinoid hyperemesis typically lasts for 24–48 hours and the problem often resolves with long term stopping of cannabis use. Improvement can take one to three months to occur.[9]

Relapses are common, and this is thought to be possibly secondary to a lack of education as many people use or increase their use of cannabis due to their symptoms of nausea and vomiting.[8]

Epidemiology[edit]

The number of people affected is unclear as of 2015,[4] though the prevalence may be in the millions.[18] Among users smoking 20 or more days per month, about one-third might experience symptoms.[19] Cannabinoid hyperemesis syndrome has been reported more frequently in people that use cannabis daily (47.9% of patients) and greater than daily (23.7% of patients), compared to once weekly users (19.4% of patients) and less frequent users (2.4% of patients).[3] A significant increase in the incidence of cannabinoid hyperemesis syndrome (and other marijuana-related visits to the emergency department) has been noted in U.S. states that have legalized marijuana, with the incidence of cyclic vomiting prominently doubling in the US state of Colorado after legalization.[16] As the use of marijuana continues to be legalized at the state level, the prevalence of cannabinoid hyperemesis syndrome is expected to increase in the US.[3]

A 2018 surveyed of 155 heavy cannabis users in hospital found 51 of them experienced cannabinoid hyperemesis syndrome.[1] This ratio was used to estimate that in the United States, 2.7 million out of 8.3 million heavy cannabis users should be experiencing the syndrome.[1] The same study found that of those who go to the emergency department in the United States with recurrent vomiting, about 6% have the condition.[1] In 2018 a 17 year old died of the condition.[20]

History[edit]

Cannabinoid hyperemesis was first reported in the Adelaide Hills of South Australia in 2004.[5]

The name cannabinoid hyperemesis syndrome was also coined at this time. The report focused on nine patients who were chronic cannabis users who presented with cyclical vomiting illness. One woman in the study reported that warm baths provided the only relief from the nausea, severe vomiting, and stomach pain and reportedly burned herself in a hot water bath three times trying to get relief.[21]

Society and culture[edit]

Cannabinoid hyperemesis syndrome is not very well known, and some healthcare providers may view it as a "rare, kind of funny disease."[22] Some emergency room physicians have referred to the symptoms as "scromiting," a portmanteau of "screaming" and "vomiting."[23] In lieu of a correct diagnosis, the average patient in the US may owe $100,000 USD or more in medical bills through emergency department visits.[22] An emergency department physician in 2018 commented that the condition wasn't on their "radar" in the 5 years prior, though the condition was being diagnosed more often now.[24] Many people are struck by the notion that cannabis could induce symptoms of nausea and vomiting, given the common perception that cannabis can be used to prevent nausea and vomiting.[24]

Research directions[edit]

It is unclear why cannabinoid hyperemesis syndrome is disproportionately uncommon in recognition of how widely used cannabis is throughout the world. There may be genetic differences between cannabis users that affect one's risk for developing cannabinoid hyperemesis syndrome. The pathophysiology of the syndrome is also unclear, especially with regards to the effect of cannabinoids on the gut. The long-term outcomes of patients that have suffered from cannabinoid hyperemesis syndrome is unknown.[8]

References[edit]

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w Chocron, Y; Zuber, JP; Vaucher, J (19 July 2019). "Cannabinoid hyperemesis syndrome". BMJ (Clinical research ed.). 366: l4336. doi:10.1136/bmj.l4336. PMID 31324702.
  2. ^ a b c Sullivan, S (May 2010). "Cannabinoid hyperemesis". Canadian Journal of Gastroenterology. 24 (5): 284–5. doi:10.1155/2010/481940. PMC 2886568. PMID 20485701.
  3. ^ a b c d e f g h i j Sorensen, Cecilia J.; DeSanto, Kristen; Borgelt, Laura; Phillips, Kristina T.; Monte, Andrew A. (20 December 2016). "Cannabinoid Hyperemesis Syndrome: Diagnosis, Pathophysiology, and Treatment—a Systematic Review". Journal of Medical Toxicology. 13 (1): 71–87. doi:10.1007/s13181-016-0595-z. PMC 5330965. PMID 28000146.
  4. ^ a b Lu, ML; Agito, MD (July 2015). "Cannabinoid hyperemesis syndrome: Marijuana is both antiemetic and proemetic". Cleveland Clinic Journal of Medicine. 82 (7): 429–34. doi:10.3949/ccjm.82a.14023. PMID 26185942.
  5. ^ a b Allen, J H; De Moore, GM; Heddle, R; Twartz, JC (2004). "Cannabinoid hyperemesis: Cyclical hyperemesis in association with chronic cannabis abuse". Gut. 53 (11): 1566–70. doi:10.1136/gut.2003.036350. PMC 1774264. PMID 15479672.
  6. ^ a b c Sontineni, Siva-P; Chaudhary, S; Sontineni, V; Lanspa, SJ (2009). "Cannabinoid hyperemesis syndrome: Clinical diagnosis of an underrecognized manifestation of chronic cannabis abuse". World Journal of Gastroenterology. 15 (10): 1264–6. doi:10.3748/wjg.15.1264. PMC 2658859. PMID 19291829.
  7. ^ a b c d e f g h i j Ruffle, James K.; Bajgoric, Sanjin; Samra, Kiran; Chandrapalan, Subashini; Aziz, Qasim; Farmer, Adam D. (December 2015). "Cannabinoid hyperemesis syndrome". European Journal of Gastroenterology & Hepatology. 27 (12): 1403–1408. doi:10.1097/MEG.0000000000000489. PMID 26445382.
  8. ^ a b c d e f g h i j k l m n o p q r s Galli, JA; Sawaya, RA; Friedenberg, FK (December 2011). "Cannabinoid hyperemesis syndrome". Current Drug Abuse Reviews. 4 (4): 241–9. doi:10.2174/1874473711104040241. PMC 3576702. PMID 22150623.
  9. ^ a b c d e f g h i j k l Sun, S; Zimmermann, AE (September 2013). "Cannabinoid hyperemesis syndrome". Hospital Pharmacy. 48 (8): 650–5. doi:10.1310/hpj4808-650. PMC 3847982. PMID 24421535.
  10. ^ a b c d Habboushe J, Sedor J (June 2014). "Cannabinoid hyperemesis acute renal failure: a common sequela of cannabinoid hyperemesis syndrome". American Journal of Emergency Medicine. 32 (6): 690.e1–2. doi:10.1016/j.ajem.2013.12.013. PMID 24418446.
  11. ^ Argamany, Jacqueline R.; Reveles, Kelly R.; Duhon, Bryson (April 2016). "Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal failure". American Journal of Emergency Medicine. 34 (4): 765.e1–765.e2. doi:10.1016/j.ajem.2015.08.051. PMID 26422191.
  12. ^ a b "NCPIC.Cannabinoid hyperemesis syndrome". Ncpic.org.au. Retrieved 23 July 2016.
  13. ^ Eskridge, KD; Guthrie, SK (1997). "Clinical issues associated with urine testing of substances of abuse". Pharmacotherapy. 17 (3): 497–510. PMID 9165553.
  14. ^ Simonetto, Douglas A.; Oxentenko, Amy S.; Herman, Margot L.; Szostek, Jason H. (2012). "Cannabinoid Hyperemesis: A Case Series of 98 Patients". Mayo Clinic Proceedings. 87 (2): 114–9. doi:10.1016/j.mayocp.2011.10.005. PMC 3538402. PMID 22305024.
  15. ^ Wallace, Erik A.; Andrews, Sarah E.; Garmany, Chad L.; Jelley, Martina J. (1 September 2011). "Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm". Southern Medical Journal. 104 (9): 659–664. doi:10.1097/SMJ.0b013e3182297d57. PMID 21886087.
  16. ^ a b c d e f g h i j Lapoint, Jeff; Meyer, Seth; Yu, Charles; Koenig, Kristi; Lev, Roneet; Thihalolipavan, Sayone; Staats, Katherine; Khan, Christopher (2018). "Cannabinoid Hyperemesis Syndrome: Public Health Implications and a Novel Model Treatment Guideline". Western Journal of Emergency Medicine. 19 (2): 380–386. doi:10.5811/westjem.2017.11.36368. PMC 5851514. PMID 29560069.
  17. ^ a b King, Chelsey; Holmes, Andrew (17 March 2015). "Cannabinoid hyperemesis syndrome". Canadian Medical Association Journal. 187 (5): 355. doi:10.1503/cmaj.140154. PMC 4361109. PMID 25183721.
  18. ^ Habboushe, Joseph. "Cannabinoid hyperemesis syndrome: What GIs should know". www.healio.com. Healio. Retrieved 10 May 2018.
  19. ^ Habboushe, Joseph; Rubin, Ada; Liu, Haoming; Hoffman, Robert S. (12 January 2018). "The Prevalence of Cannabinoid Hyperemesis Syndrome Among Regular Marijuana Smokers in an Urban Public Hospital". Basic & Clinical Pharmacology & Toxicology. 122 (6): 660–662. doi:10.1111/bcpt.12962. PMID 29327809.
  20. ^ "'It's torture': Is a mysterious cannabis-related illness underdiagnosed in Canada?". CBC. Retrieved 18 November 2019.
  21. ^ Brodwin, Erin (15 February 2019). "A mysterious syndrome in which marijuana users get violently ill is starting to worry researchers". Business Insider. Archived from the original on 26 March 2019. Retrieved 26 March 2019.
  22. ^ a b Rabin, Roni (9 April 2018). "Marjuana linked to 'unbearable' sickness across US as use grows following legalisation". The Independent. Retrieved 10 May 2018.
  23. ^ Hamill, Jasper (20 April 2018). "Weed smokers need to carefully avoid 'scromiting' when getting high on 420 Day". Metro. Retrieved 10 May 2018.
  24. ^ a b Bartolone, Pauline. "'I've screamed out for death': Heavy, long-term pot use linked to rare, extreme nausea". USA TODAY. Retrieved 10 May 2018.

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