Cannabinoids: Emerging Evidence in Use and Abuse (Pharmacology CME)
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Table of Contents
 

<< Cannabinoids and “Legal Highs”, Table of Contents

Course 1: Cannabinoids: Emerging Evidence in Use and Abuse + EMplify podcast audio summary

As the use of cannabinoids increases, so have ED presentations of patients with acute intoxication and cannabinoid hyperemesis syndrome. This issue reviews the latest evidence on recognizing and managing patients with emergent conditions related to cannabinoid use, including:

An overview of the pathophysiology of cannabinoids.

Current evidence on the common and uncommon clinical findings associated with cannabinoid use: neurologic, psychiatric, cardiovascular, renal, metabolic, oral, and ophthalmologic.

How synthetic cannabinoids can be similar to - and different from - natural and "medical" cannabis products.

How to determine when laboratory testing is indicated, and when it is not.

A look at the current evidence on cannabinoid hyperemesis syndrome, including some emerging management strategies for this commonly misdiagnosed condition.

The latest information on the legal and FDA approval status of cannabinoid drugs.

Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Critical Appraisal of the Literature
  5. Etiology and Pathophysiology
    1. Synthetic Cannabinoids
    2. Current Indications for Cannabinoids
    3. Routes of Administration
    4. Clinical Findings Associated With Acute Use
      1. Neurologic Effects
      2. Psychiatric Effects
      3. Cardiovascular Effects
      4. Pulmonary Effects
      5. Renal Effects
      6. Metabolic Effects
      7. Oral/Dental Effects
      8. Ophthalmologic Effects
      9. Cannabinoid Hyperemesis Syndrome
    5. Withdrawal
  6. Differential Diagnosis
  7. Prehospital Care
  8. Emergency Department Evaluation
    1. History
    2. Physical Examination
  9. Diagnostic Studies
    1. Laboratory Testing
    2. Electrocardiogram
    3. Imaging
  10. Treatment
    1. Treatment for Acute Cannabis and Synthetic Cannabinoid Toxicity
    2. Treatment for Cannabinoid Hyperemesis Syndrome
  11. Special Populations
    1. Pediatric Patients
    2. Pregnant Women
  12. Controversies and Cutting Edge
    1. Legal Status of Cannabis/Cannabinoids
    2. Haloperidol for Cannabinoid Hyperemesis Syndrome Treatment
    3. Capsaicin for Cannabinoid Hyperemesis Syndrome Treatment
  13. Disposition
  14. Summary
  15. Risk Management Pitfalls for Management of Acute Cannabis Use
  16. Key Points
  17. Time and Cost-Effective Strategies
  18. Case Conclusions
  19. Clinical Pathway for Emergency Department Management of Cannabinoid Hyperemesis Syndrome
  20. Tables
    1. Table 1. Main Constituents of Cannabis Sativa
    2. Table 2. Peak Plasma Concentration Times of THC via Various Routes of Administration
    3. Table 3. Symptoms and Findings for Clinical Diagnosis of Cannabinoid Hyperemesis Syndrome
    4. Table 4. Differential Diagnosis for Suspected Cannabis Intoxication
    5. Table 5. Differential Diagnosis of Intractable Vomiting
    6. Table 6. Drugs Implicated in False-Positive Cannabinoid Screening
  21. References
Listen to the podcast for this course

Abstract

Despite current legal and medical controversies surrounding cannabinoids, it is a fact that emergency departments are seeing an increasing number of patients presenting with symptoms associated with the use of these drugs. This review outlines the pathophysiology of cannabinoids, the potential clinical findings associated with their use, and the current evidence for best-practice management of patients who present to the emergency department with signs of acute intoxication and chronic use. Differences between natural and synthetic cannabinoids are discussed, along with the latest evidence for diagnosing and managing patients presenting with the intractable vomiting of cannabinoid hyperemesis syndrome. Emerging treatments for cannabinoid hyperemesis syndrome are presented, including hot water bathing, early haloperidol administration, and topical capsaicin, in addition to an update on the legal status of medical cannabinoid substances.

Case Presentations

A 25-year-old woman is found at a bus stop by bystanders after a “syncopal” episode. The patient was seen stumbling as she attempted to board a bus, and she exhibited an apparent lack of coordination. Upon arrival to the ED, the patient states that she feels fine, and “everything is OK. I only smoked a little pot.” On evaluation, the patient is seated comfortably on the stretcher and is pleasant during the history and physical examination. She reports a past medical history of anxiety, but nods off during questioning. Her vital signs are: heart rate of 107 beats/min; respiratory rate, 16 breaths/min; blood pressure, 135/77 mm Hg while seated; temperature, 37.2°C; and oxygen saturation, 98% on room air. Upon examination, you note the patient has conjunctival injection, dry oral mucosa, and tachycardia, but an otherwise unremarkable examination, including neurologic assessment. At the end of your encounter, the patient says “thanks,” and requests to leave the ED for work. You wonder whether she should have a syncope workup and be kept in observation. Because you suspect marijuana intoxication, you wonder whether she should be advised to not go to work.

As you proceed to log into the EMR, EMS arrives with a 17-year-old previously healthy boy with tachycardia and violent behavior. The patient’s mother called 911 because she found him behaving strangely when she arrived home from work. The patient appears very agitated and is unable to remain seated on the stretcher during the clinical encounter. The patient reports chest pain and palpitations. His vital signs are: heart rate, 146 beats/min; blood pressure, 169/99 mm Hg; respiratory rate, 21 breaths/min; temperature, 38°C; oxygen saturation, 100% on room air; and fingerstick glucose, 65 mg/dL. Could this be an overdose or toxic ingestion? What further diagnostic tests and/or interventions should be initiated, if any?

Toward the end of your shift, a 52-year-old man writhing in pain and retching repeatedly is wheeled in by the triage nurse. He has made frequent visits to the ED over the past 2 years for abdominal pain and intractable vomiting. The patient reports that his symptoms have become so severe over the last 2 months that he has had to visit the ED frequently to gain relief, and he has lost approximately 10 pounds over the last 4 weeks. Within the last 2 months, he notes that he has had multiple blood draws in the ED and by his primary care doctor, ultrasounds of the abdomen and kidneys, 2 CT scans of the abdomen/pelvis, and an esophagogastroduodenoscopy, revealing chronic gastritis, with no evidence of peptic ulcer disease or Helicobacter pylori. The patient states that his symptoms are usually very difficult to control, and he is frequently admitted and later discharged home with a diagnosis of gastritis, only to return again the next month. His vital signs are unremarkable. You develop a differential for intractable vomiting and ask the patient a key question that leads to the diagnosis…

Introduction

According to the National Conference of State Legislatures, as of June 2018, there are 31 states, the District of Columbia, and 2 United States territories possessing state and local-level laws allowing for the use of cannabis in medicinal and/or recreational formulations.1 As of 2015, marijuana maintains the highest lifetime, past-year, and past-month use of all illicit drugs used within the United States and within all age categories. There are currently 22.2 million past-month users of marijuana among persons aged 12 or older, followed by pain relievers (3.78 million), cocaine (1.88 million), and tranquilizers (1.87 million).2,3 Recent studies in Colorado, where both medicinal and recreational marijuana use have been decriminalized and later legalized, have revealed a nearly 2-fold increase in the prevalence of emergency department (ED) visits and hospitalizations that the authors suggest may be due to marijuana exposure.4,5

Despite controversial beliefs that cannabis has no accepted medical use,1,6 its use for medical purposes has been documented as far back as 600 BC, from its suspected origin in West and Central Asia.7 Throughout its long history, cannabis use for medicinal purposes has been documented in Sanskrit, Hindi, Greek, and Western European literature for the treatment of diseases such as pretreatment for migraines, seizure disorders, tetany/spastic disorders, rheumatoid disorders, trigeminal neuralgia, asthma, and the inability to sleep.7,8 Currently, cannabis and cannabinoids are being used in the treatment of chronic pain syndromes, complications of multiple sclerosis and paraplegia, weight loss due to appetite suppression in HIV/AIDS, chemotherapy-induced nausea and vomiting, and many neuropsychiatric disorders, including seizure disorder. Nonetheless, there is an absence of high-quality evidence to support the use of cannabis and cannabinoids for any of these indications.9

To date, the use of cannabis for all purposes has been largely limited by the United States Department of Justice Drug Enforcement Administration (DEA) listing of cannabis as a Schedule I substance6, rendering its use illegal at the federal level. The DEA designation further hinders the ability both to conduct research at any level, as well as any possibility of obtaining funding from the federal government for such research.7 There is much variation in legislation at both the state and local levels of government concerning dispensaries, retail sales, and the various formulations of cannabis-containing products.1

The lack of federal regulations on the chemical content of available cannabis leads to much product variation. This variation may increase the number of patients presenting to the ED due to accidental overdose leading to toxicity.5

This issue of Emergency Medicine Practice reviews the emerging evidence on the basic pathophysiology of the endocannabinoid system, describes common presentations of acute intoxication due to marijuana and synthetic cannabinoids, identifies common characteristics and distinguishing factors of cannabinoid hyperemesis syndrome (CHS), and outlines the current and emerging treatment and disposition practices for CHS.

Critical Appraisal of the Literature

A search of PubMed and the Cochrane Database of Systematic Reviews was conducted for articles published from 1950 to 2018 using the following search terms: cannabis, marijuana, synthetic cannabinoids, cannabimimetic, and cannabinoid hyperemesis syndrome. The PubMed search produced numerous retrospective studies, predominantly case reports, case series, case reviews, systematic reviews, and meta-analyses. There were few randomized prospective studies identifying the medical applications for cannabis use, the adverse effects of cannabis and synthetic cannabis use, and the current options used in the treatment of acute cannabis/synthetic cannabinoid intoxication and CHS. The majority of literature available within the Cochrane Database evaluates the role of cannabis in the treatment of various chronic disorders; it offers no information on the adverse effects associated with acute cannabis intoxication. Additional historical information was obtained from book chapters and materials available via the Internet (such as government documents). The National Guideline Clearinghouse provided no resources for cannabis intoxication and cannabis-related disorders.

Risk Management Pitfalls for Management of Acute Cannabis Use

1. “The patient just smoked K2/Spice. He complains only of flank pain with a normal urinalysis, he doesn’t need any labs. He can sit in the corner until he is sober.”
 
Patients presenting to the ED after smoking synthetic cannabinoids will likely present to the ED with neuropsychiatric and cardiovascular complaints. However, patients presenting with abdominal or flank pain, and/or nausea and vomiting after the acute use of cannabis/ cannabinoids may be susceptible to acute kidney injury, and should have further diagnostic testing performed; in this case, urinalysis, basic metabolic profile (for BUN and creatinine), and CPK levels if rhabdomyolysis is suspected.
 
3. “This patient always comes in for intractable nausea and vomiting due to smoking cannabis. His abdomen is rigid and diffusely tender, but I don’t think he needs any further evaluation.”
 
Patients presenting to the ED due to CHS should have a full evaluation in the ED if they present with signs and/or symptoms consistent with intra-abdominal pathology. Patients with an “acute” abdomen should have a full evaluation, including radiologic testing, despite the history of CHS.
 
10. “The 11-year-old patient with a history of cyclical vomiting syndrome currently prescribed pantoprazole by her family physician presented to the ED due to nausea and vomiting. I ordered a urinalysis, urine pregnancy, and urine toxicology test as part of the evaluation and found the urine positive for THC. I considered calling child protective services.”
 
Patients may have a false-positive test for THC after using medications such as pantoprazole, ibuprofen, and efavirenz. Before alerting authorities in response to what may be a false-positive test, with its potential ramifications to the child and the family, consider the patient's medication history.

Tables

Table 3. Symptoms and Findings for Clinical Diagnosis of Cannabinoid Hyperemesis Syndrome

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

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  2. Azofeifa A, Mattson ME, Schauer G, et al. National estimates of marijuana use and related indicators - National Survey on Drug Use and Health, United States, 2002-2014. MMWR Surveill Summ. 2016;65(11):1-28. (US government statistical report)
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  73. Corvi F, Querques G, Lattanzio R, et al. Central retinal vein occlusion in a young patient following cannabis smoke inhalation. Eur J Ophthalmol. 2014;24(3):437-440. (Case report; 1 patient)
  74. Bajgoric S, Samra K, Chandrapalan S, et al. Cannabinoid hyperemesis syndrome: a guide for the practising clinician. BMJ Case Rep. 2015. DOI: 10.1136/bcr-2015-210246 (Case report; 1 patient)
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  76. Sontineni SP, Chaudhary S, Sontineni V, et al. Cannabinoid hyperemesis syndrome: clinical diagnosis of an underrecognised manifestation of chronic cannabis abuse. World J Gastroenterol. 2009;15(10):1264-1266. (Case report; 1 patient)
  77. Habboushe J, Rubin A, Liu H, et al. The prevalence of cannabinoid hyperemesis syndrome among regular marijuana smokers in an urban public hospital. Basic Clin Pharmacol Toxicol. 2018;122(6):660-662. (Prevalence study; survey of 155 patients)
  78. Beech RA, Sterrett DR, Babiuk J, et al. Cannabinoid hyperemesis syndrome: a case report and literature review. J Oral Maxillofac Surg. 2015;73(10):1907-1910. (Case report; 1 patient)
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  80. Galli JA, Sawaya RA, Friedenberg FK. Cannabinoid hyperemesis syndrome. Curr Drug Abuse Rev. 2011;4(4):241-249. (Review)
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