It is difficult to establish the cause–effect relationship between marijuana use and cardiovascular disease. A review of the literature was undertaken to compare our case with other reported occurrences of cannabis-related MI. A MEDLINE search using the words “marijuana” AND “myocardial infarction” yielded 36 cases of acute coronary events likely triggered by the consumption of marijuana. The majority of these patients were male (33, 92%) with a mean age of 30.9 years (median 30, range 17–51), and eight patients (22%) died. A similar search using the words “cardiac arrest” AND “sudden cardiac death” AND “marijuana” resulted in 30 reported episodes. Similarly, most of these patients were male (28, 93%) with a mean age of 34.6 years (median 31, range 15–61). In eight patients (27%), other recreational drugs were also found in toxicology screen (in five of these patients (63%), serum alcohol levels were positive). Twenty-five patients (83%) died. An acute cardiovascular event was the probable cause of death in all these subjects. Summary of cases of cardiac arrest and sudden cardiac death related to marijuana consumption is shown in Table 1. The patient described in this report paired the characteristics of those previously reported events: male gender, young adult, positive serum alcohol levels, and had an unfavorable outcome. Unfortunately, our patient was not able to be transferred to another institution for coronary angiography and possible percutaneous angioplasty because of his hemodynamic instability and elevated FIO₂ requirements. As previously outlined by Elmer et al., patients with recreational drug-related out-of-hospital cardiac arrests are less likely to undergo cardiac catheterization (21). It is possible that our patient might have had a non-diagnosed underlying coronary artery disease that may have been aggravated by the consumption of marijuana. This may be supported by the presence of a calcified apical thrombus, which suggests chronicity. It has been suggested that consumption of THC may worsen coronary ischemia in patients with baseline coronary artery disease, potentially triggering an MI (8).

The pathophysiological effects of marijuana in the cardiovascular system are well described, and they seem to be mediated by stimulation of the sympathetic nervous system through release of norepinephrine as well as by parasympathetic nervous system blockade (26). However, the mechanism underlying the association between marijuana use and MI has not been well established. It has been demonstrated that consumption of marijuana increases oxygen demands on the myocardium, leading to an increase in carboxyhemoglobin levels resulting in decreased oxygen-carrying capacity (27, 28). The rise in norepinephrine levels resulting from sympathetic stimulation reduces the left ventricular ejection time, thereby lowering the threshold for angina. Interference with the integrity of peripheral vascular reflex responses and vascular inflammation with the subsequent increase in platelet activation have been also proposed as mechanisms responsible for cardiac events among cannabis users (29, 30). Reversible vasospasm seems to be the most commonly suggested etiology for cannabis-associated acute coronary syndromes. One study showed that cardiovascular complications resulting from the consumption of marijuana have a mortality rate of about 25% (31). In a large epidemiological study, THC and its derivatives were reported to increase the risk of MI by 4.8 times in the first hour after use (32). Another cohort showed that in marijuana consumers, the population attributable fraction for MI was 0.8% (33).

It is unclear why our patient developed seizures before going into cardiac arrest. The relation between marijuana use and epileptic seizures is still controversial. Although cannabis is not commonly associated with seizures and may actually have medical use benefits for the treatment of epilepsy (34), there have been reports of seizures resulting from acute THC intoxication (2, 3). Even though prolonged cardiac arrest leads to hypoxia, which may result in seizures, we do not consider hypoxemia to be the leading cause of seizures in this case given the initial cascade of events, since our patient was initially presented with tonic–clonic seizures that were followed by a cardiac arrest. It is possible that our subject developed seizures because of the synergistic effect of marijuana and alcohol consumption (35). It is also feasible that the patient described in this report might have been under the effects of other recreational drugs unable to be identified by using conventional toxicology screens. Seizures have been reported to be a frequent feature of synthetic cannabinoids intoxication (36, 37). Unfortunately, we were not able to collect any analytical data on synthetic cannabinoids from our patients’ serum except from a negative urine toxicology assay. Our subject's urine toxicology screen failed to detect the presence of synthetic cannabinoids, making the role of these substances unlikely in our patient's clinical presentation. We hypothesized that the development of cardiac arrest in our patient was the result of an extensive ST-segment elevation MI, in conjunction with the ventricular fibrillation likely triggered by myocardial ischemia. It is possible that the onset of ventricular fibrillation may have been provoked by tonic–clonic seizures, as previously reported in few other cases (38, 39). As a consequence of the prolonged CPR time and hypoxemia, severe global anoxic brain injury was developed that led to brain death. There have been previous similar reports of sudden cardiac deaths related to marijuana consumption. Dines et al. reported an 18-year-old male who succumbed to an asystole cardiac arrest while smoking marijuana and suffered hypoxic brain injury related to prolonged cardiac arrest (2). Similarly, Hartung et al. described a 23-year-old male who collapsed with ventricular fibrillation and died after 40 min of unsuccessful CPR (17). In a large cohort of patients with recreational drug overdose-related out-of-hospital cardiac arrests, brain death accounted for more than 30% of fatalities (21). Ventricular fibrillation has been sporadically reported as a result of marijuana consumption (2, 16). A possible explanation for the onset of ventricular dysrhythmias is that cannabis may increase the activity of the Purkinje fibers system (6, 40). The combination of alcohol with marijuana could potentially increase the cardiac toxicity and arrhythmogenic effects of THC by alteration of atrial refractoriness and conduction velocity.

Our report has two potential limitations: first, the initial ECG strip recorded by EMS showing ventricular fibrillation was not able to be recovered, so it is difficult to comment on the rhythm obtained after electrical cardioversion was delivered; second, no blood levels of THC were obtained on admission and, therefore, it may be difficult to attribute the etiology of this acute coronary event directly to the consumption of marijuana. Postmortem toxicological tests were not performed. A positive urine toxicology screen for THC may be insufficient evidence in the linkage of cardiac arrest and marijuana. THC analysis in blood samples must be considered an essential requirement to estimate and correlate the time of last intake with the occurrence of acute cardiovascular events. Unfortunately, the association of marijuana consumption and the occurrence of cardiovascular events is rarely supported by an exhaustive toxicological examination and, when such investigation is performed, it is usually limited to a positive urine toxicological examination that is not reliable for the estimation of the time of last marijuana intake. In this case, as in majority of the previously reported events, the cannabis causality was assumed based on the result of a positive urine toxicology screen for THC and the absence of other substances known to be linked to acute coronary syndrome.