Bradycardia and Cannabinoid Hyperemesis Syndrome (CHS): two clinical pictures that are increasingly seen in the Emergency Department.
What are cannabinoids?
Cannabinoids are a series of extremely liposoluble chemical substances present in the Cannabis sativa plant. The most pharmacologically active among them is the delta-9-tetrahydrocannabinol (Δ9-THC). The prolonged or intense use of high doses of cannabis[1] could lead to acute cannabinoid intoxication causing bradycardia and cannabinoid hyperemesis syndrome (CHS).
What do cannabinoids do in our body?
Cannabinoids are chemical substances that interact with two types of receptors present in the human body:
- CB1
CB1 is a class of receptors distributed mainly in the central nervous system, but it is also found in the peripheral nervous system, the lungs, heart, and liver. The activation of this class of receptor at the central level causes a release of dopamine from the brain producing euphoria, analgesia, perceptual alteration, reduction of memory, and motor control. At the peripheral level, it inhibits the response of the sympathetic system, causing vasodilation and tachycardia.
- CB2
CB2 is a class of receptors present at the peripheral level, in particular in the cells of the lymphoid system. They are implicated in the reduction of the inflammatory response and the reduction of hyperalgesia.
Who uses cannabinoids?
In Europe and the United States, cannabinoids are recreational drugs. Young people between 18 and 25 are main users[2]. In addition, cannabioids are used for medical-therapeutic purposes. For instance, in treating vomiting and nausea caused by chemotherapy, to stimulate appetite in AIDS patients, to treat chronic pain and muscle stiffness caused by multiple sclerosis, and in the treatment of depression.
What are the symptoms?
The common belief is that the intake of even large quantities of cannabinoids is harmless. However, subjects with acute cannabinoid intoxication are present more and more frequently in emergency departments (EDs) or clinics. They present a vast array of symptoms, including nausea, cyclical vomiting, agitation, short-term memory loss, cognitive deficits, psychosis, seizures, and arrhythmias. In addition, symptoms associated with the sympathetic system activation, such as mydriasis, hypertension, and tachycardia, are often described.
In the ED, what should we pay attention to?
There are two particularly relevant clinical pictures related to acute cannabinoid poisoning: CHS and bradycardia.
What is cannabinoid bradycardia?
The effects of cannabinoids on the heart depend on their dosage. At a low to moderate dose, there is tachycardia and arterial hypertension (through an increase in the activity of the sympathetic nervous system); at a high dose, there is sinus bradycardia, hypotension, and decreased myocardial contractility[3],[4]. The beginning of the arrhythmic effect peaks at 30 minutes from the intake and can last several hours. In the literature, the arrhythmic effects are described together with cases of sinus tachycardia, sinus bradycardia, atrioventricular blockages, and cardiac arrest.
What is CHS?
CHS is characterized by episodes of prolonged cyclic vomiting, with an average duration of 24–48 h, accompanied by abdominal pain separated by extended periods (even months) of an absence of symptoms. These episodes of vomiting are incredibly resistant to conventional therapy using drugs, such as metoclopramide, ondansetron, or promethazine. In addition, the acute phases can be so severe as to be responsible for dehydration, water, and electrolyte disturbances and disorientation.
How do we diagnose CHS?
The diagnosis of CHS is clinical and can potentially be represented by the triad:
- Marijuana use over a prolonged period;
- Intractable vomiting that can last for hours or days and does not respond to the common anti-emetic therapy; and
- Improvement of symptoms after a hot shower or hot bath or use of topical capsaicin.
However, this syndrome enters into differential diagnosis with psychogenic vomiting, cyclic vomiting syndrome [5], and hyperemesis gravidarum [6],[7].
How do we treat CHS?
First of all, resuscitation through the administration of fluids and electrolytic rebalancing are priorities. After that, CHS seems to resolve a few minutes after a hot shower or bath [8] or the use of topical Capsaicin cream applied in a thin layer at the abdominal, thoracic, or lumbar level[9]. However, the reasons for such therapy are not yet clear. In addition, Haloperidol[10] and the use of Beta-blockers[11] were also found to be effective in the treatment of CHS. After medical treatment, it is important to educate the patient about cannabinoid hyperemesis and to inform how the cessation of cannabinoid use can resolve this clinical picture.
What is the take-home message?
The liberalization of the laws on the use of cannabinoids and a growing favorable public opinion about them will likely increase acute cannabinoid intoxication cases in the EDs. In conclusion, a better knowledge of these two clinical pictures among emergency clinicians could avoid costly and time-consuming tests, scans, and procedures in these patients.
References
- Smart R, Caulkins JP, Kilmer B, Davenport S, Midgette G. Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state. Addiction. 2017 Dec;112(12):2167–77.
- National Institute on Drug Abuse. Nationwide Trends. 2015; https://www.drugabuse. gov/publications/drugfacts/nationwide- trends. Accessed May 26, 2018.
- Pacher, P., Steffens, S., Haskó, G. et al. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol 15, 151–166 (2018) doi:10.1038/nrcardio.2017.130
- David O. Andonian, Shauna R. Seaman, Elaine B. Josephson, Profound hypotension and bradycardia in the setting of synthetic cannabinoid intoxication – A case series The American Journal of Emergency Medicine, Volume 35, Issue 6, June 2017, Pages 940.e5-940.e6
- Bhandari S, Jha P, Thakur A, Kar A, Gerdes H, Venkatesan T. Cyclic vomiting syndrome: epidemiology, diagnosis, and treatment. Clin Auton Res. 2018 Apr;28(2):203–9.
- Alaniz VI, Liss J, Metz TD, Stickrath E. Cannabinoid hyperemesis syndrome: a cause of refractory nausea and vomiting in pregnancy. Obstet Gynecol. 2015 Jun;125(6):1484–6
- Volkow ND, Compton WM, Wargo EM. The Risks of Marijuana Use During Pregnancy. JAMA. 2017 Jan;317(2):129–30
- Lapoint J, Meyer S, Yu CK, Koenig KL, Lev R, Thihalolipavan S, et al. Cannabinoid Hyperemesis Syndrome: Public Health Impli- cations and a Novel Model Treatment Guideline. West J Emerg Med. 2018 Mar; 19(2):380–6.
- Graham J, Barberio M, Wang GS. Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series. Pediatrics. 2017 Dec;140(6):e20163795.
- Hickey JL, Witsil JC, Mycyk MB. Haloperidol for treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med. 2013 Jun; 31(6): 1003.e5–6.
- Richards JR, Dutczak O. Propranolol Treatment of Cannabinoid Hyperemesis Syn- drome: A Case Report. J Clin Psychopharmacol. 2017 Aug;37(4):482–4.
