On April 23, 2014, the Journal of the American Heart Association (JAHA) published an article titled “Cannabis Use: Signal of Increasing Risk of Cardiovascular Disorders.”¹

The authors of the JAHA article worked with the French Addictovigilance Network (FAN) to analyze cases in which cardiovascular complications were reported to the network alongside cannabis (Cannabis sativa, Cannabaceae) use for the years 2006 through 2010. (FAN was “created in the 1990s with the aim of achieving reliable surveillance of abuse and pharmacodependence cases related to drug abuse.”¹) According to the study, healthcare providers in France have a “legal obligation to report to their regional addictovigilance center all serious cases defined as one of the following criteria of seriousness: leading to temporary or permanent functional incapacity or disability, to inpatient hospitalization or prolongation of existing hospitalization, to congenital anomalies, or to an immediate vital risk or death.”¹

During the five years investigated, a total of 9,936 reports were filed with FAN for all drugs. Of those, 1,979 cases were cannabis related. From there, only 35 involved cardiovascular complications and cannabis use, nine of which were fatal. (As a result, based on these somewhat limited data, part of the authors’ conclusion is that a death rate of 25.6% exists in cases of cardiovascular complications related to cannabis.¹) Inclusion criteria were adequate documentation with outcome chronology; however, cases with insufficient patient management and toxicological information also were admitted, as noted below. Research was funded by the French InterMinisterial Mission for the Fight Against Drugs and Addiction and the French Drug Agency.¹

The various shortcomings of the study — many of which will be elucidated herein — signal the need for critical analysis of the data and even skepticism toward the validity of the authors’ conclusions.

As noted by the JAHA authors, cardiovascular diseases (CVDs) are the world’s leading causes of death. Well-known risk factors include age, tobacco and/or alcohol use, obesity, physical inactivity, and high blood pressure and/or cholesterol. According to the World Health Organization, behavioral risk factors such as tobacco and/or alcohol use, poor diet, and physical inactivity are to blame for 80% of incidences of coronary heart disease and cerebrovascular disease.² Other concerns include genetics (familial history of CVD), sex (pre-menopausal women have a lower risk), secondhand-smoke exposure, kidney disease, low birth weight, and intake of substances such as caffeine or pharmaceuticals such as sildenafil (the active ingredient in Viagra^®).

Cannabis has been posited as a potential trigger for coronary events. According to a 2002 Journal of Clinical Pharmacology article, “THC [tetrahydrocannabinol] acutely causes a substantial increase in heart rate (as high as 50%-60%) that is dose dependent and is generally associated with a modest increase in blood pressure, whether smoked in marijuana cigarettes or administered intravenously. Maximal heart rate increase occurs 10-15 minutes after peak plasma THC concentration.”³ Tolerance develops to the acute effects.²

Conversely, in several recent studies^4-6 cannabinoids have exhibited potential cardioprotective properties, according to Jahan Marcu, PhD, multidisciplinary scientific advisory board vice-chair of Americans for Safe Access, a medical cannabis patient advocacy organization (email, May 4, 2014). “Cannabis-based medicine and cannabinoids are being developed to treat ischemia and other pathologies due to heart attacks,” said Dr. Marcu. “Cannabinoids protect the heart from damage, stimulate repair mechanisms of cardiac tissues, and are being developed to reduce brain damage from heart attacks.”

While the possibility exists that individuals with cardiovascular risks could be adversely affected by cannabis intake, a study of 65,171 subjects over the course of 49 years showed no significant difference in mortality rate between cannabis users and non-users.⁷

The mean age of the JAHA subjects was 34.3; 30 of the patients were men; 21 of the patients were tobacco smokers; and no associated substances were declared in 11 cases. (As previously stated, both men and tobacco smokers are at a higher risk for CVD.) Seven patients had a familial cardiovascular history and nine had personal cardiovascular history, adding up to 16 — a total of 46% of the subjects.¹

In seven of the nine fatal case reports, patients had either already collapsed or were found dead and more than likely would not have been able to contribute relevant details to their medical files — including vital information about associated substances for which they may not have been tested. No case descriptions or toxicology information were presented for the other two fatalities. Fatal cases for which patient management information was not available totaled five.

Patients’ exposure to cannabis was broken down into three categories: actual, recent, and regular/daily. In eight of the nine fatal cases, exposure was actual, defined as “one or more uses in the past 12 months,” while recent refers to one to nine uses in the past 30 days. In the article, several case descriptions seem to disagree with reported exposure. In one fatal 2009 case, exposure was classified as actual when the case description reports the presence of cannabinoids “at a dose compatible with recent intoxication.” The case description for a 2010 case states that the deceased was under the influence of cannabis, but exposure is listed as actual. Another fatal 2010 case classifies exposure as actual, though the case description notes “[c]hronic exposure to cannabis.”

Many other cardiac risk factors are not mentioned among the data and do not seem to be considered by the authors, including the subjects’ physical inactivity, kidney disease, history of substance abuse, stress level, exposure to secondhand smoke, blood lipid disorder(s), caffeine intake (usually not considered a cardiac risk factor), et al.

Several sources for this article highlighted the fact that cannabis is most frequently smoked along with tobacco in France (a country with a relatively high per-capita tobacco-smoking population⁸), thereby cautioning that the cases in which cannabis is the sole “associated substance” in this article should be considered with a considerable degree of skepticism where toxicology testing does not confirm that a subject was in fact tobacco-free.

“There’s a tendency for folks who are of the…drugs-are-bad kind of mindset that leads to a gross over-interpretation and a tendency to not just cherry-pick…but to just completely turn things inside out,” said William Dolphin, publications director of Americans for Safe Access (personal communication, May 2, 2014). “This study comes [from people] who are looking at negative outcomes, and fair enough — that’s the lens that they’re interpreting it through,” said Dolphin, adding, “You tend to find what you look for and there are all kinds of that kind of observational bias that get through to the media and then the media take it and amplify it.”

“Now, the caveat to all of that — and it’s a serious concern — is that the elevated heart rate, the vasodilation can be problematic for some people,” explained Dolphin. “If you’ve got a heart problem, you shouldn’t be using Viagra, you shouldn’t be engaging in really strenuous exercise, and maybe you shouldn’t be going near the cannabis — IF you know it creates that effect in you.”

Skewed and poor-quality cannabis studies, whether their outcomes are positive or negative, highlight the need for research of high methodological quality in this area. Despite a long history of relatively safe use, legitimate concerns regarding the effects of cannabis and its many unique compounds demand robust and critical study, particularly as more people have access to legal medicinal and recreational cannabis. In the United States, the erroneous view that cannabis is a highly dangerous substance with no redeeming medicinal value perpetuates its frequently-criticized Drug Enforcement Agency Schedule I classification, which in turn makes it more difficult to attain approval for medical research. That the American Heart Association allowed such an inadequate cannabis study to be published under its auspices is troubling. When correlation is spun as causation and resultant media coverage is uncritical and misleading, scientific and public health progress is hindered.

—Ash Lindstrom

References

1. Jouanjus E, Lapeyre-Mestre M, Micallef J, French Association of the Regional Abuse and Dependence Monitoring Centres Working Group on Cannabis. Cannabis use: signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc. 2014;3:e000638; originally published April 23, 2014; doi: 10.1161/JAHA.113.000638. Available at: http://jaha.ahajournals.org/content/3/2/e000638.full.pdf+html.
2. Cardiovascular diseases fact sheet. World Health Organization website. Available at: www.who.int/mediacentre/factsheets/fs317/en/. Accessed May 19, 2014.
3. Sidney S. Cardiovascular consequences of marijuana use. J Clin Pharmacol. 2002;42:64S-70S.
4. Wang Y, Ma S, Wang Q, et al. Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci China Life Sci. 2014;57(2):201-208.
5. Rudź R, Schlicker E, Baranowska U, et al. Acute myocardial infarction inhibits the neurogenic tachycardic and vasopressor response in rats via presynaptic cannabinoid type 1 receptor. J Pharmacol Exp Ther. 2012;343(1):198-205.
6. Hillard CJ. Role of cannabinoids and endocannabinoids in cerebral ischemia. Curr Pharm Des. 2008;14(23):2347-2361.
7. Sidney S, Beck J, Tekawa I, Quesenberry C, Friedman G. Marijuana use and mortality. Amer J Pub Health. 1997;87(4):585-590.
8. WHO Report on the Global Tobacco Epidemic, 2013. World Health Organization website. Available at: www.who.int/tobacco/surveillance/policy/country_profile/fra.pdf?ua=1a. Accessed June 5, 2014.