Marijuana and Cardiovascular Disease

Marijuana use—whether recreational or therapeutic—is controversial. Although further research is required to definitively determine the impact of marijuana on cardiovascular disease, physicians should use caution in advising or treating any patient with an impaired heart and considerable risk factors.

The legal use of cannabis for either medical or recreational use is growing. Twenty-eight states and the District of Columbia, Guam, and Puerto Rico now have laws legalizing marijuana, and legislatures in several states that recently passed legalization measures are debating regulatory proposals for the use and sale of marijuana. According to the Drug Enforcement Administration (DEA)1 marijuana extract is defined as: “an extract containing one or more cannabinoids that has been derived from any plant of the genus Cannabis, other than the separated resin (whether crude or purified) obtained from the plant.” Extracts of marijuana will continue to be treated as Schedule I controlled substances.

In response to California’s Proposition 215, the Institute of Medicine issued a report that examined the potential therapeutic uses for marijuana.² The report found that there is data to support potential therapeutic value of cannabinoid drugs—primarily tetrahydrocannabinol (THC)—for pain relief, as well as to stimulate the appetite and control nausea and vomiting. Marijuana in its smoked form, however, is a crude THC-delivery system that also delivers harmful substances. There are psychological effects, such as anxiety reduction, sedation, and euphoria, that may be potentially undesirable for certain patients and beneficial for others, and some of these effects can complicate the interpretation of other aspects of the drug’s effect. Marijuana has also been found to be effective in relieving some of the symptoms of HIV/AIDS, cancer, glaucoma, and multiple sclerosis^.3,4

There are similar studies that show the risks associated with the use of marijuana. Longitudinal studies have shown the harmful effects on lung function² and the increased risk of schizophrenia and psychosis.⁵ The recent study by Kalla et al⁶ that was presented at the American College of Cardiology’s 66th Annual Scientific Sessions in Washington, DC, this past May cautions us about the risk of recreational and medicinal use in a population with established cardiovascular disease or in people with an increased risk of heart disease.

Along with the wider use of legalized marijuana, debate is growing about whether marijuana should be used or allowed in patients with cardiovascular disease (CVD), such as coronary artery disease (angina), cerebrovascular disease, and end-stage heart failure, either for recreational use or the clinical benefits of pain relief and control. Physicians can expect to encounter more patients who use or abuse marijuana. Therefore, cardiologists need to be aware of its effects on the cardiovascular system. Because of restrictions on manufacturing and distribution, there is a paucity of validated clinical studies describing the cardiovascular and other systemic effects of marijuana. The observational study by Kalla et al6 cautions us to avoid its use in patients with heart conditions. There are other studies that failed to prove long-term effects on cardiovascular mortality.^7,8 However, most of the studies mentioned above are observational and experimental animal studies, and there are no randomized human studies. We will discuss some other reasons to avoid or be cautious with the use of marijuana in patients with heart disease or at the risk of developing heart disease.

CARDIAC PATHOPHYSIOLOGY

Atherosclerosis

The active ingredient in marijuana is THC. Its receptors are present in almost every organ in the body. Hence, cannabinoids can have multiple effects on the body. Some states that have legalized medical marijuana—including Texas, Louisiana, North Carolina, and South Carolina—have only approved low-THC, high-cannabinoid versions.

There are 2 types of cannabinoid receptors in humans. Cannabinoid receptor type 1 (CB1) activation is pro-atherogenic and cannabinoid receptor type 2 (CB2) activation is anti-atherogenic. Cannabinoids modulate the immune system, alter lipid metabolism, and affect endothelial cells and vascular smooth muscle cells (VSMCs). The biological effects of cannabinoids are nullified and have not translated into a reduction or an increase in atherosclerosis in clinical trials such as STRADIVARIUS (Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant—the Intravascular Ultrasound Study)9 and AUDITOR (Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant)¹⁰.

EFFECT ON THE CARDIOVASCULAR SYSTEM

In humans, marijuana use is associated with increased heart rate and postural fluctuations in blood pressure, which may be implicated in developing heart attacks or strokes.11 Multiple case reports of acute coronary syndrome after marijuana use have been published in the literature. More recently, a study in the Journal of the American Heart Association reported that there are potential cardiovascular dangers to young adults using marijuana.¹² One study found an elevated risk up to 4.8 times higher for myocardial infarction (MI) within 1 hour of smoking marijuana.13 In patients with a history of MI, marijuana use more than once a week was associated with a 3-fold increase in mortality.14 A longitudinal CARDIA study published in February 2017 by Reis et al⁷ concluded that compared with no marijuana use, cumulative lifetime and recent marijuana use showed no association with incident CVD, stroke or transient ischemic attacks, coronary heart disease, or CVD mortality. Marijuana use was not associated with CVD when stratified by age, gender, race, or family history of CVD.

Apart from the effects that active-ingredient marijuana has on the body, the delivery method for the drug raises other concerns. Substances within the inhaled smoke, such as carbon monoxide and burnt plant particles, can harm lung tissues and damage small blood vessels. This is like tobacco smoking, which can have negative effects on the heart and can also lead to strokes, especially in patients with existing heart and circulatory problems.

There are no definitive, rigorous scientific studies to guide us about marijuana use because the drug was illegal for many decades. All the observational studies have limited credibility due to other confounding factors such as genetic manipulation of marijuana types and strains, quantification of the use, adverse health behaviors—such as increased calorie intake, obesity, tobacco, alcohol, and cocaine use, and association with HIV.¹⁵ The effects are unpredictable. The study by Kalla et al,⁶ has similar limitations. Even adjusting for these factors, the actual cardiovascular risk may be over- or underestimated.

CONCLUSION

Our knowledge about the potential benefit of marijuana is limited. Given the potential adverse effects, its use for a specific disease should be done under a doctor’s supervision. Long-term studies have failed to show a definite increase in cardiovascular mortality with marijuana use. Even with those studies, it is hard to justify anyone with cardiovascular disease using marijuana because there isn’t valid information to know how it will affect their hearts.

REFERENCES

1. Drug Enforcement Administration, Department of Justice. Establishment of a new drug code for marihuana extract. December 14, 2016. https://www. federalregister.gov/documents/2016/12/14/2016-29941/establishment-of-anew- drug-code-for-marihuana-extract. Accessed July 17, 2017.

2. Ribeiro LI, Ind PW. Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review. NPJ Prim Care Respir Med. 2016;26:16071. doi: 10.1038/npjpcrm.2016.71.

3. Lutge EE, Gray A, Siegfried N. The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD005175. doi: 10.1002/14651858.CD005175.pub3.

4. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456-2473. doi: 10.1001/jama.2015.6358.

5. Hall W, Degenhardt L. Cannabis use and the risk of developing a psychotic disorder. World Psychiatry. 2008;7(2):68-71.

6. Kalla A, Krishnamoorthy P, Gopalakrishnan A, Figueredo VM. Cannabis use predicts risks of heart failure and cerebrovascular accidents: results from the National Inpatient Sample. J Am Coll Cardiol. 2017;69(11 Suppl):1784. doi: 10.1016/S0735-1097(17)35173-2.

7. Reis JP, Auer R, Bancks MP, et al. Cumulative lifetime marijuana use and incident cardiovascular disease in middle age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Public Health. 2017;107(4):601-606. doi: 10.2105/AJPH.2017.303654.

8. Sidney S, Beck JE, Tekawa IS, et al. Marijuana use and mortality. Am J Public Health. 1997;87(4):585-590.

9. Nissen SE, Nicholls SJ, Wolski K, et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA. 2008 Apr 2;299(13):1547-1560. doi: 10.1001/jama.299.13.1547.

10. O’Leary DH, Reuwer AQ, Nissen SE, et al. AUDITOR investigators. Effect of rimonabant on carotid intima-media thickness (CIMT) progression in patients with abdominal obesity and metabolic syndrome: the AUDITOR Trial. Heart. 2011;97(14):1143-1150. doi: 10.1136/hrt.2011.223446.

11. Kattoor A, Mehta JL. Marijuana and coronary heart disease. American College of Cardiology. www.acc.org/latest-in-cardiology/articles/2016/09/22/08/58/marijuana-and-coronary-heart-disease. September 22, 2016. Accessed July 5, 2017.

12. Jouanjus E, Lapeyre-Mestre M, Micallef J. Cannabis use: signal increasing risk of serious cardiovascular disorders. J Am Heart Assoc. doi: 10.1161/JAHA.113.000638.

13. Mittleman MA, Lewis RA, Maclure M, et al. Triggering myocardial infarction by marijuana. Circulation. 2001;103(23):2805-2809.

14. Mukamal KJ, Maclure M, Muller JE, Mittleman MA. An exploratory prospective study of marijuana use and mortality following acute myocardial infarction. Am Heart J. 2008;156(3):465-470. doi: 10.1016/j.ahj.2007.10.049.

15. Rodondi N, Pletcher MJ, Hulley SB, Sidney S. Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study). Am J Cardiol. 2006;98(4):478-484.