Author: Sateesh Bidaisee
Department: Department of Public Health and Preventive Medicine.
St. George’s University and Windward Islands Research and Education Foundation,
Corresponding Author: firstname.lastname@example.org
The use of recreational cannabis has been rapidly increasing in the United States of America and it is heavily accelerated by recent decriminalization and legalization movements. It has been gaining greater popularity among adolescents and young adults due to the perception of low health risk of cannabis and improved accessibility. Consequently, there has been increasing number of cases being reported for acute coronary syndrome (ACS) related to recreational cannabis use in people who are otherwise healthy and do not have any cardiac history. The pathophysiology of cannabis-induced ACS is rather poorly understood, yet there is general agreement among physicians that cannabis-induced diffuse transient coronary vasospasm and sympathomimetic properties of cannabis are the underlying mechanism of cardiac manifestations. The purpose of this review is to discuss the relationship between ACS and recreational cannabis use and to raise an issue that its potential severe health outcomes pose a public health concern, which should warrant strengthening the regulations related to recreational cannabis use.
The use of recreational cannabis has been gaining greater popularity in North America over the past two decades. The rapid increase in recreational cannabis has been heavily accelerated by recent decriminalization and legalization movements. Decriminalization refers to a policy where possession or use of small amounts of cannabis would involve a civil penalty but not criminal prosecution, thus, it is treated like a traffic violation. On the other hand, legalization allows cultivation, commercial distribution and possession for recreational purpose. As of 2018, 10 states and the District of Columbia have legalized recreational cannabis and 13 other states have decriminalized its use and possession in the United States of America. Cannabis remains prohibited at the federal level although federal laws are not enforced in states with decriminalization or legalization. In October 2018, Canada has fully legalized the use of recreational cannabis across the whole nation where the government controls its production, distribution and sales. Worldwide, cannabis is the most popular recreational drug, apart from tobacco and alcohol products, with global number of users approaching 182.5 million, which is about 3.8% of global population .
The popularity of recreational cannabis is well reflected by its numerous nicknames. While Cannabis is the scientific nomenclature of the genus name of the plant, marijuana (which refers to dried plant form, will be used interchangeably in this review) is probably the most commonly used term but there are also other names like weed, pot, joint, dope, 420, sticky icky, etc. Its principle psychoactive ingredient, delta 9-tetrahydrocannabinol, along with many other cannabinoids in the plant, produce some immediate desired effects including relaxation, euphoria, increased awareness of sensation, increased libido and alteration of conscious perception.
The widespread use of recreational cannabis stems from the perception of low health risk profile of cannabis despite its well-established psychoactive properties. People commonly believe that smoking marijuana only harms as much as regular cigarette smoking but less addictive than cigarette and also believe it is a much safer alternative compared to other illicit drugs that gives a high like cocaine or methamphetamine.
Cannabis has also long been considered as a “gateway drug” meaning that the people who first tried recreational cannabis (while it may be still illegal) tend to move on with other types of illicit substance later. According to National Institute on Drug Abuse (NIDA), marijuana is responsible for 70.3% of first-time illicit drug use . In a study conducted with participants in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), it was concluded that 44.7% of individuals with lifetime cannabis use have progressed to other illicit drug use at some time in their lives .
What we really have to be cautious about is the following question ‘Is it actually safe?’ The psychoactive properties of cannabis are very well-studied in numerous scientific researches; however, its adverse effects on cardiovascular system have not been rigorously pursued and they are rather poorly understood. There has been increasing number of cases of acute coronary syndrome (ACS) related to acute cannabis abuse . What is more remarkable is the fact that many of these ACS cases were occurred in young and otherwise healthy individuals who did not have any cardiac history . The purpose of this paper is to provide the information about causal relationship between recreational cannabis use and ACS and to suggest its negative public health impacts.
Prevalence of Recreational Cannabis
As mentioned above, cannabis is the most commonly abused recreational drug in the United States of America. In 2013, 7.5% (19.8 million) of the U.S. population aged ≥12 years reported using marijuana during the preceding month . In 2014, a total of 2.5 million persons aged ≥12 years had used marijuana for the first time during the preceding 12 months, an average of approximately 7,000 new users each day . The trend of recreational marijuana has been rapidly increasing since mid-2000s which is inevitably influenced by liberalization of laws regarding recreational cannabis and improved accessibility. National prevalence of perceived availability (that is, fairly or very easy to obtain marijuana) for persons aged ≥12 years was 60.2% in 2014 .
Popularity in Adolescents and Young Adults
It is worth to note that marijuana gained significantly more popularity among younger individuals. In 2017, a national survey reported that 6.8% of grade school students had tried marijuana for the first time before age 13 years and 19.8% of grade school students had used marijuana one or more times during the 30 days before the survey . The prevalence was significantly higher among black (25.3%), Hispanic (23.4%) then white (17.7%) students when compared to all other race or ethnic groups . The prevalence increased with higher grade level and it was also found that the prevalence of U.S. 12th-grade students who used marijuana was even greater than that of cigarettes use .
Low Perception of Health Risk
It is a common belief that cannabis has low risk of adverse health effects. Consequently, there has been increased social acceptance of recreational cannabis in the United States. It has been shown in the 2017 national survey that the proportion of persons aged ≥12 years who think smoking marijuana poses great health risk was only 26.5% . In addition, the perceived parental disapproval of minors trying marijuana had decreased by 6.0% between 2002 and 2014 . A decrease in the perception of health risk from smoking marijuana combined with increases in the perception of availability and fewer punitive legal penalties for the possession of marijuana for personal use explains the increased use among the younger population .
Role in Acute Coronary Syndrome
As we experience rapid increase in recreational cannabis, hospitals are encountering more patients with acute cannabis abuse and along with that, there are increasing number of cases of ACS including full blown myocardial infarction (MI) in young and otherwise healthy individuals [4, 8]. The pathophysiology of cannabis-induced ACS and MI is rather poorly understood. Yet there is general agreement among physicians that cannabis-induced diffuse transient coronary vasospasm and increased sympathetic activities (especially increase in heart rate and supine blood pressure) of cannabis are the underlying mechanism of ACS where the coronary angiography reveals free of atherosclerotic pathology . Its clinical presentation looks similar to cocaine induced MI’s in young patients with recreational drug abuse. The difference is that we know the molecular mechanism of how cocaine works in which it inhibits catecholamine reuptake at sympathetic nerve terminals, hence, there is increase in sympathetic output as well as overt vasoconstriction. With cannabis, we know the likely outcomes but the detailed molecular mechanism is yet to be discovered. Nevertheless, there are a few other hypotheses on how cannabis may contribute to development of ACS.
As recreational cannabis is mostly being smoked it would increase the concentration of carboxyhaemoglobin in the blood, therefore, resulting in decreased oxygen carrying capacity of red blood cells and decreased myocardial oxygen supply . This is the issue with any type of smoking including smoking regular cigarettes. However, even though this is a plausible explanation it is not sufficient to cause ACS alone because we do not find people having MI from acute chain smoking itself. The effects of smoking on the heart is accumulated over long periods of time through atherosclerosis and plaque rupture. Yet, carboxyhemoglobin could contribute, at least transiently while smoking, to the mismatch between oxygen requirement of heart muscles and oxygen supply delivered by coronary arteries.
Platelet Activation and Pro-coagulant Effects
It has also been proposed that cannabis has pro-coagulant effects through CB1 and CB2 receptors found on platelet cell membrane . In vitro study has shown that cannabis increases expression of glycoprotein IIb-IIIa and P-selectin in a concentration dependent manner which leads to platelets aggregation and Factor VII activation . Cannabis is also postulated to exert hemodynamic effects which could initiate plaque rupture and promote thrombosis; however, there are contradicting research studies where they have found that CB1 receptor activation is pro-atherogenic, while CB2 receptor activation is antiatherogenic . In addition, in vivo studies have failed to show the same pathogenic outcome and opinions are also mixed. Cannabis induced platelet activation and its pro-coagulant effects are considered rather debatable among researchers at this time.
Apart from ACS, cannabis is also considered to have arrhythmogenic properties. Elevation of heart rate is one of the consistent effects of cannabis smoking which can last up to two to three hours . Korantzopoulos et al. noted that cannabis smoking might be associated with atrial fibrillation with hypothesis that adrenergic stimulation reduces duration of action potential and alters the electrophysiological properties of myocardium to favor automaticity and micro-reentry thereby promoting development of atrial fibrillation in susceptible individuals . Casier et al. also reported a case of fatal ventricular fibrillation after smoking marijuana in a patient with pre-existing coronary artery disease . The development of cardiac arrhythmias after cannabis smoking can potentially increase the risk of sudden cardiac death. Cannabis is commonly used among young persons in social settings and the combined use of marijuana with other illicit substances is quite frequent. Therefore, it is also important to consider synergistic effects of cannabis and other stimulant drugs because when combined together they will worsen the risk of potential arrhythmias.
Quantitative Analysis between Cannabis and ACS
There are a few studies aimed to assess the causality between cannabis and ACS by quantitative analysis. Older studies have already shown that in patients with chronic stable angina, smoking a single roll of marijuana decreased exercise time to angina threshold by 48% when compared to placebo. In a case-crossover analysis of 3882 patients with acute MI, it was shown that there is 4.8 elevated risk of MI within one hour of marijuana use and the risk declines rapidly after one hour . The same study revealed that the relative risk of acute MI for cocaine is 24 while it is 4.8 for marijuana. Since many of quantitative studies were done prior to liberalization of recreational cannabis we can expect more effective sampling and statistical significance if the same study design were to be repeated nowadays.
There are a number of synthetic cannabinoid varieties including K2 and Spice which are more accessible and common in the United States. The most serious concern for synthetic cannabis is that we do not know the exact chemical composition. There are indeed many different types of cannabinoids where tetrahydrocannabinol is merely only one of at least 113 identified so far. Since we do not know the exact chemical composition or if there were anything other than cannabinoids added, adverse effects are much more unpredictable. There has been a case report of cardiac arrest in previously healthy 16-year-old after synthetic cannabis use . Many of these synthetic compounds are prohibited in the United States as well as internationally.
Public Health Effects of Recreational Cannabis
Increased abuse potential of cannabis among adolescents and young adults and their perception of cannabis that it is relatively harmless do pose serious public health concerns. While the prevalence of recreational cannabis is continuously increasing, appropriate regulations regarding its safe use are still lacking. Its psychoactive properties decrease the cognitive function and sensory perception which would become a problem with complex tasks that innately require higher cognitive function and sensory processing such as driving. Cannabis is the most frequently detected illicit drug (it is still illegal under federal law regarding traffic and motor vehicle safety act regardless of state law) involved in motor vehicle crashes and the evidence from experimental and epidemiological studies indicates that cannabis significantly impairs driving performance and increases crash risk .
Cannabis-induced ACS and MI are largely underrepresented because previously the occurrence was very rare; however, with a rapid increase in prevalence of recreational cannabis it is expected to see more cases of ACS which should reveal the clinical significance of cannabis on cardiovascular health. Currently, there is not enough clinical data about cannabis in relation to dose-dependent cardiotoxicity nor are there official guidelines in the amount of cannabinoid content among regulated cannabis products. We have regulations and government guidelines for alcohol in this respect. Further research studies are required to explain the molecular basis of cardiac effects as well as to create appropriate regulations for public health.
Economic Effects of Cannabis
Legalizing recreational cannabis opens up a new industry which seems very strong and sustainable at this point. This would bring an increased tax revenue to the government and provide substantial economic growth to the local economy. The economic benefit has been well proven in the example of Colorado where cannabis has been legalized as of 2014. The revenue per calendar year has been steadily increasing, and with sales of medical and recreational cannabis the overall revenue since 2014 has reached almost one billion dollars and Colorado collected more than 135 million dollars in taxation and related fees . The tax revenue generated from cannabis industry is then used for the state’s Public-School Capital Construction Assistance Fund, and public programs such as substance abuse and regulation of marijuana use to ensure that any adverse effects caused by the legalization were paid for by its own generated tax revenue .
Long-Term Cardiovascular Effects
Although acute cardiac effects of cannabis are generally agreed among physicians, the long-term cardiovascular effects are largely unknown so far. In a cohort study that followed up 5113 sample adults for more than 25 years, they found marijuana use was not associated with increased risk of cardiovascular disease (CVD) when stratified by age, gender, race and family history of CVD . On the other hand, a cross-sectional study in Egypt has concluded that cannabis smoking could be a potential risk factor for the development of cardiac ischemia owing to coronary artery disease . It is actually difficult to solely assess the long-term effects of cannabis whether it is contributing to the development of atherosclerosis. This is because the vast majority of people who smoke marijuana also smoke cigarettes regularly, and smoking is a very well-known risk factor for atherosclerosis.
Advancement of molecular biology is continuously unveiling the mechanism of endocannabinoid system and its physiological function in cardiovascular health. Physiological effects of cannabis on CB1 and CB2 receptors and their role in atherosclerosis development are currently under investigation by multiple researchers. Studies for direct effect of smoked cannabis exposure on plasma lipids have shown somewhat variable results among different research studies, but inhibition of CB1 receptor using CB1 antagonist have consistently shown relative improvements in weight, plasma triglyceride and high-density lipoprotein cholesterol . Cannabis effect on lipid profile is an important remark for long-term vascular health.
Cannabis-induced ACS would become more apparent as prevalence of recreational cannabis continuously increases along with decriminalization and legalization. Sooner or later it will come to a point that we need more detailed regulations in regard to cannabis use to ensure the public health and prevent adverse health outcomes. It is yet too early to conclude what are the effects of cannabis but continuous data collection and research should produce meaningful results in a few years.
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