Marijuana Edible Linked to Myocardial Infarction

Batya Swift Yasgur MA, LSW

February 15, 2019

Consumption of marijuana might have adverse cardiac effects, especially in older individuals with a history of cardiac disorders, a case report suggests.

Two Canadian physicians report the case of a 70-year-old man with stable coronary artery disease (CAD), who consumed a lollipop containing a large quantity of delta-9-tetrahydrocannabinol (THC) to relieve pain and aid sleep.

The patient subsequently presented to the emergency department (ED) with hallucinations and cardiac symptoms, and was eventually diagnosed with non-ST-elevation myocardial infarction (MI), successfully treated, and discharged.

"One of the reasons we published this case report is that we don't have a whole lot of data on what marijuana does to people with CAD," Alexandra Saunders, MD, Dalhousie University Internal Medicine Program, and Horizon Health Network, Department of Cardiology, Saint John, New Brunswick, told theheart.org | Medscape Cardiology.

"Some case reports have looked at young men and at established users rather than a marijuana-naïve person," but the current report highlights concerns about the impact on older adults as well as people with CAD, she said.

The report was published online February 11 in the Canadian Journal of Cardiology.

"Pan–North American Experience"

Marijuana is becoming increasingly popular as widespread legalization makes it both more accessible and more acceptable, and marijuana use on the rise in all age groups, including the elderly.

Legalization of marijuana and the resulting confusion this might cause for clinicians in how to guide patients is a "pan–North American experience," said coauthor Robert S. Stevenson, MD, Horizon Health Network, Department of Cardiology.

"What prompted this case report was that, as a cardiologist, I felt flat-footed when I was in the ED and this patient with established coronary disease presented and, as the details unfolded, I realized I wasn't familiar with the impact of marijuana on this population," he told theheart.org | Medscape Cardiology.

"With the legalization of marijuana in Canada, I realized we'll be seeing much more of this," he said.

Saunders agreed, stating that she recently completed a rheumatology rotation and was "really surprised at the number of older people — perhaps as many as 75% of patients on any given day — who would never have even considered the idea of marijuana and were now asking if they could use it for pain."

She noted that many older people with arthritis do not find current agents sufficient for pain management and many are considering marijuana as an alternative.

Additional reasons beyond pain that older adults turn to marijuana often are to alleviate insomnia and anxiety.

Paranoia, Hallucinations

The 70-year-old man with stable CAD and no angina presented with crushing chest pain, diaphoresis, fearful hallucinations, and pallor that began 30 minutes after he consumed most of a lollipop that contained 90 mg of THC.

Although the patient had smoked marijuana as a young man, he had been cannabis-naïve for decades and had never ingested it in oral form.

The patient had previously had four coronary bypass graft surgeries and also had hypertension, dyslipidemia, type 2 diabetes mellitus, a more than 30-pack-year smoking history, and a family history of cardiac disease.

He was being treated with an array of medications, including daily aspirin, perindopril, rosuvastatin, metoprolol, metformin, glyburide, pantoprazole, and zopiclone.

The patient was treated for non-ST-elevation MI with a low-molecular-weight heparin bolus, acetylsalicylic acid, and clopidogrel, and discharged home after his hallucinations and chest pain had resolved.

A follow-up nuclear medicine study performed 12 days later found worsening ejection fraction, compared with a 2015 finding, and the patient described reduced functional status and exertional tolerance after the event.

The patient was advised to abstain from consuming similar quantities in the future and has not retried marijuana lollipops since.

"People with heart attacks typically experience distress, but this went above and beyond — he had agitation, paranoia, and terror that something bad might happen to him, which clearly went beyond the physical distress of the heart event itself," Stevenson said.

Mechanisms of Cardiac Effects

Cannabis contains several compounds, including THC and cannabidiol (CBD). Saunders suggested that THC, which is what has the psychoactive effects, caused the patient's fear response and hallucinations, "which caused him to go into overdrive, have a more rapid heartbeat and elevated blood pressure, leading to a supply-and-demand problem, as the heart couldn't get as much blood because of already narrowed arteries."

Additionally, "THC might have a proinflammatory response, potentially causing damage to the lining of the blood vessels and making a vulnerable person at further risk for heart attack."

An accompanying editorial by Neal Benowitz, MD, Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, Department of Medicine, and Biopharmaceutical Sciences, Center for Tobacco Control Research and Education, San Francisco, elucidated the mechanism by which cannabis jeopardizes cardiac health.

Cardiovascular toxicity might be a consequence of the inhalation of the combustion products of marijuana, when that is the mode of delivery.

However, even in edible form, THC can have direct cardiovascular effects by acting on cannabinoid receptor 1, primarily through central nervous system (CNS) pathways, thereby increasing sympathetic nervous system activity.

In turn, this results in a dose-related tachycardia, increased myocardial contractility, supine hypertension, and systemic catecholamine release.

Catecholamine can reduce coronary blood flow by constricting coronary vessels and/or activating platelets, with a "net effect" of a "substantial increase in myocardial work and oxygen demand, combined with impairment in the expected and necessary compensatory increase in coronary blood flow."

High doses of THC — and even lower doses in THC-naïve individuals — can also impair cognition and create feelings of loss of control that can lead to high levels of distress.

He noted that the patient consumed a dose much higher than would be prescribed for a THC-naïve person — for example, dronabinol (Marinol), a synthetic THC marketed for nausea and vomiting in patients undergoing cancer chemotherapy, would be 2.5 mg for an older patient, and the maximum recommended dose for any patient is 20 mg/day.

"Extreme emotional responses in the context of THC psychiatric toxicity are associated with the surges of catecholamines, which can have adverse acute CV effects," he writes.

Counseling Patients

Saunders emphasized that it is important to ask patients of all ages about marijuana use; in fact, she said, "we've added it to our routine list of questions."

"Historically, it would have been unusual to ask a 72-year-old woman about marijuana use and we would have received a quizzical look. But today, without concerns about legal issues, patients are interested and only too happy to talk about it," she added.

Stevenson also includes discussion of marijuana in his "usual preamble to any patient in the office."

He does not "typically refer patients to medical marijuana, as there are only limited indications — for example, for intractable nausea in chemotherapy or for certain types of seizures."

"If patients choose to use marijuana recreationally, it's their choice and it's legal, but that doesn't make it safe," he continued.

Patients should be informed of this and of potential adverse effects, he said.

THC vs CBD

Commenting on the case for theheart.org | Medscape Cardiology, Thorsten Rudroff, PhD, assistant professor, Department of Health and Human Physiology and Department of Neurology, University of Iowa, Iowa City, who was not involved with the report, called it "very important and interesting, even though it is only a case study."

The outcome was "not a big surprise" for him.

"The patient took cannabis with a very high THC content and we know nothing about the side effects of THC in these patients" or how cannabis interacts with the multiple other medications this patient was taking, he said.

Rudroff agreed with the authors that cannabis use in older people is becoming increasingly common, which is problematic because older people typically are taking multiple medications, "and we don't know anything about how cannabis interacts with them."

The patient in the study had smoked cannabis as a young man, but "you can't compare today's products to what was available when this man was in college," Rudroff pointed out.

"The THC content in today's cannabis has increased significantly since the Woodstock generation, when a joint had maybe 3% to 5% THC. Now, we have products that can go up to 90% THC," he said.

He noted that pain relief comes from CBD, whereas "THC is the problem-maker."

Rudroff is currently researching the impact of cannabis on patients with multiple sclerosis (MS).

"Neuroimaging with fMRI in these patients has shown changes in glucose uptake in specific brain areas typically responsible for psychoactive effects of THC, and we have found that THC can increase anxiety, depression, and hallucinations, which is already a problem with patients with MS," he said.

However, "we have four patients who used high-CBD products with low THC and reported no bad things; in fact, the opposite was the case."

The CBD "increased activity in brain areas that reduce pain and other symptoms."

He advised that patients who wish to use cannabis use a high-CBD and low-THC product, noting, however, that it can be difficult to ascertain the reliability of the products.

"We have no choice but to trust the labels on the product, but the problem is that many products are not labeled accurately," he noted.

Stevenson agreed. "The biochemical theory behind CBD is that it is supposed to be more helpful and tone things down rather than ramping them up as THC does," he said. However, "CBD products are often contaminated with THC."

Stevenson pointed to a recent recall of CBD products in the New Brunswick area because of excessive quantities of THC.

Further Research Needed

"We see increased exposure to marijuana and we should be equipped to deal with it, and we're hoping that publishing this case history will raise awareness of the problem and lead to more research, publications, and advisories," Saunders said.

Rudroff agreed that there is a paucity of research into cannabis, including its impact on older people and its interaction with other drugs.

In the meantime, several Canadian organizations have issued statements regarding medical marijuana use, Saunders said, including the Canadian Medical Association and the College of Family Physicians of Canada, and one from the Ontario Medical Association on recreational cannabis use. These might be used as starting points for clinicians.

Saunders, Stevenson, and Rudroff report no conflicting interest. Benowiotz has been a consultant to Pfizer and GlaxoSmithKline, pharmaceutical companies that market medications to aid smoking cessation, and has served as a paid expert witness in litigation against tobacco companies.

Can J Cardiol. Published online February 11, 2019. Abstract, Editorial

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