By: Jeng Lee, PharmD Candidate c/o 2022

              Throughout the past decade, there has been an increase in the prevalence of medical and recreational consumption of cannabis, also referred to as marijuana. ¹ These numbers are expected to rise over the upcoming years in the United States as marijuana use is currently legalized in 33 states and the District of Columbia.¹ Despite that, medical marijuana is currently not approved by the US Food and Drug Administration (FDA) for the treatment of any health diseases. ² Marijuana is obtained from the hemp plant, Cannabis sativa. ³ Cannabis contains two main active ingredients, delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD).¹ These constituents can be found in varying levels depending on the species of cannabis. ¹ Marijuana produces psychoactive effects and inflammatory actions via THC and CBD respectively.¹ THC binds to the Cannabinoid 1 and 2 receptors (CB1 and CB2) with high selectivity.³ CB1 receptors are primarily expressed in the brain and other tissues, such as cardiac muscle, hepatic tissue, the gastrointestinal tract, and vascular endothelium.³ On the other hand, CB2 receptors are predominantly expressed in immune cells and have newly demonstrated to be involved in the regulation of inflammatory cytokines.³ CB1 receptors are typically located in multiple locations, including the cardiovascular system (CVS), the central nervous system (CNS), and peripheral vasculature.³

Unlike marijuana, tobacco consumption has been popular since the late 18th century. ⁴  Approximately 23% of the world population smokes cigarettes, with a higher prevalence in men than in women.⁴ Tobacco, also called Nicotiana tabacum, is derived from the leaves of the tobacco plant, and can be commonly found in cigarettes and cigars. Tobacco products often contain many other toxic substances, such as carbon monoxide, polycyclic aromatic hydrocarbons (PAHs), nicotine, and heavy metals, amongst others.⁴ These components have a concerning impact on the vascular endothelium, blood lipids, and thrombotic factors, which in turn may result in detrimental cardiovascular events, including myocardial infarction, stroke, and aortic dissection.⁵ Additionally, the inhalation of tobacco smoke leads to an increase in the levels of exogenous and endogenous free radicals in the body; thus, resulting in higher levels of oxidative stress that may disrupt the normal cell and tissue function. ⁴

It is widely known that smoking can have various negative effects on the body. Tobacco use is one of the most preventable causes of cardiovascular diseases (CVDs).⁵ Cigarette smoking can cause damage via multiple pathways, including but not limited to inflammation, endothelial dysfunction, prothrombosis, altered lipid metabolism, and increased demand for but reduced supply of myocardial oxygen and blood, also known as demand-supply mismatch.⁵ Furthermore, tobacco consumption impacts the cardiovascular system by increasing catecholamine release, which results in vasoconstriction as well as an increase in cardiac output and heart rate. ⁵ Inflammation is the primary mechanism of CVD as it is involved in atherosclerosis initiation and progression, and the occurrence of cardiovascular events.⁵ Inflammatory markers, such as white blood cells, fibrinogens, interleukin-6, and other proteins, act as indicators for blood vessel damage, and are found to be elevated in tobacco users.⁵ Various chemicals in tobacco smoke play a role in the development of CVD by influencing the oxygen demand-supply balance of the heart muscle.⁵ Nicotine stimulates the sympathetic system, leading to an increase in myocardial oxygen demand by heart rate and blood pressure elevation along with an increase in myocardial contractility. Simultaneously, myocardial blood supply is diminished via endothelial dysfunction and vasoconstriction. ⁵

Currently, marijuana is viewed as safe or even beneficial by the general population. However, this may be an issue as there is insufficient and conflicting data in regard to the effects of cannabis on many health conditions, including CVDs.⁶ The endocannabinoid system (ECS) exerts its effects through both the sympathetic and parasympathetic nervous systems.¹ As a result, cannabis consumption causes an immediate rise in heart rate and supine blood pressure, with the tachycardia mediated primarily via activation of the CB1 receptor.¹ Similarly to tobacco use, the consumption of marijuana also has a negative impact on myocardial oxygen demand and supply, where there is an increase in the former and a decrease in the latter.¹ This is the result of high levels of carboxyhemoglobin from smoking marijuana.¹ As a consequence, cannabis users can develop transient myocardial ischemia and can experience other cardiovascular effects, such as a reduction in exercise-related cardiac performance or weakened myocardial contraction.¹

Furthermore, there have been several case reports, such as Basnet et al. and Gunawardena et al., indicating an association between THC and coronary vasospasm-induced cardiomyopathy. ³ Both case studies involved young and otherwise healthy individuals, who demonstrated symptoms of CVD along with elevated ST-segment in the electrocardiogram (ECG) and high blood troponin levels.³ Both individuals admitted to marijuana consumption^{. 3} Since both patients were young and had no medical conditions, the case studies appear to show some correlation between the use of cannabis and these cardiovascular adverse effects.

Comparable to tobacco, marijuana also contains many toxic compounds, such as acetaldehyde, ammonia, benzene, carbon monoxide, hydrogen cyanide, PAHs, and so on. ³ Thus, these chemicals may be responsible for the cardiovascular effects experienced by marijuana users^{. 3} Additionally, it is common that fungi spores invade into the marijuana plant. ³ The main fungal species of concern is the Aspergillus species, which can generate aflatoxins. ³ This is potentially harmful as it can result in severe acute cardiovascular effects, including but not limited to, protein synthesis disruption in cardiac muscle cells and mitochondrial disruption in the heart tissue.³ Moreover, aflatoxins can persist for long periods of time on the cannabis plant, in marijuana joints as well as the water used in “bongs”. ³ Therefore, increasing the exposure of cannabis users to these destructive cardiovascular effects.

In contrast, there have also been a few studies demonstrating no connection between marijuana consumption and CVDs. A moderate-ROB (risk of bias) CARDIA-based (Coronary Artery Risk Development in Young Adults) study assessed the correlation between cumulative lifetime marijuana consumption and cardiovascular mortality.⁶ The investigation found no association between cannabis consumption, with a cumulative of 5 or more years, and cardiovascular mortality.⁶ Additionally, this study examined the composite outcome of cardiovascular mortality, stroke, and coronary heart disease, which also found no correlation between marijuana consumption of 5 or more years and the composite outcome.⁶ Another moderate-ROB prospective study, based on CARDIA, once again found that there was no association between the exposure to cannabis and stroke^{. 6}

 Overall, although marijuana has a lot of similar substances and mechanisms of action as tobacco on the cardiovascular system, it still remains unclear if cannabis has the same negative impact on the heart that tobacco does. Despite that, it is also uncertain that marijuana consumption can have positive and beneficial cardiovascular effects. Hence, users may be advised to limit marijuana consumption, if possible, or to evaluate the advantages and disadvantages of cannabis use depending on their circumstances. More research studies are required on the effect of cannabis use and CVDs as there is currently still inadequate evidence on the subject.

Sources:

1. Latif Z, Garg N. The impact of marijuana on the cardiovascular system: A review of the most common cardiovascular events associated with marijuana use. J Clin Med. 2020; 9 (6): 1925. Published 2020 Jun 19.
2. Turner AR, Agrawal S. Marijuana. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430801/ .
3. Subramaniam VN, Menezes AR, DeSchutter A, et al. The cardiovascular effects of marijuana: Are the potential adverse effects worth the high?. Mo Med. 2019; 116 (2): 146-153.
4. Adam Tn, Morris J. Smoking. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537066/ .
5. Roy A, Rawal I, Jabbour S, et al. Chapter 4: Tobacco and cardiovascular disease: A summary of evidence. In: Prabhakaran D, Anand S, Gaziano TA, et al., editors. Cardiovascular, Respiratory, and Related Disorders. 3 rd edition. Washington (DC): The International Bank for Reconstruction and Development/The World Bank; 2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525170/ .
6. Ravi D, Ghasemiesfe M, Korenstein D, et al. Associations between marijuana use and cardiovascular risk factors and outcomes: A systemic review. Ann Intern Med. 2018; 168 (3): 187-194.

Published by Rho Chi Post