Small Arrhythmia Risk Seen When Medical Cannabis Used for Pain

New users of medical marijuana for the treatment of chronic pain appear to have a greater risk of developing arrhythmias, according to a Danish registry study published recently online in the European Heart Journal.

The absolute increase in risk was 0.4% through the first 180 days compared with other patients who had chronic pain, with the difference lessening out to 1 year, researchers led by Anders Holt, MD (Copenhagen University Hospital—Herlev and Gentofte, Denmark), report.

Differences in absolute risk of arrhythmias through 180 days were greatest in the subsets of patients with cancer (1.1%) or cardiometabolic disease (0.8%). Hazards of ACS, stroke, and heart failure, however, did not seem to be influenced by use of medical cannabis.

Taken together, the findings are not a reason to panic, Holt indicated, pointing out that the observational study cannot prove causation. “Medical cannabis might be associated with a risk of arrhythmia, although the risk is very small,” he told TCTMD. “More research is certainly needed in this area if we are going to be prescribing medical cannabis for chronic pain, [but] don’t refrain from trying medical cannabis if other treatment is inadequate. . . . Just be aware and look out for any new symptoms immediately following this medication.”

Agreeing was Robert Page II, PharmD (University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora), who wrote an accompanying editorial.

Although “any arrhythmia is not a good arrhythmia,” he told TCTMD, there is not enough here to make a blanket recommendation against trying medical cannabis for chronic pain.

“I think what these data do is allow medical providers and patients to make better informed decisions,” Page said. “It just means that when looking at pharmacotherapy options for pain, all of this has to be contextualized so that you are able to find a good pain regimen that works for a patient.”

Filling a Knowledge Gap

Recreational pot use has been linked to adverse cardiovascular effects in prior observational studies, the researchers note.

“The active cannabinoid compounds in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), interact with the endocannabinoid system and have been associated with elevated heart rate, hypotension, and increased cardiac oxygen demand—in relation to recreational cannabis use,” Holt et al write. “Moreover, recreational cannabis use has been associated with an increased risk of arrhythmia and, to a lesser extent, acute coronary syndrome.”

There are, however, limited data on potential side effects with medical cannabis. That’s unusual with prescription drugs, which typically are studied extensively in clinical research before being brought to market, Holt underscored.

The investigators aimed to start to fill that gap by examining data from nationwide health registries in Denmark, which started to allow prescriptions of medical cannabis for chronic pain in 2018. Of about 1.88 million patients with chronic pain identified between 2018 and 2021, 5,391 (median age 59 years; 63.2% women) received a first-time prescription for medical cannabis. These patients were matched 1:5 by age, sex, chronic pain diagnosis, and concomitant use of other pain medications with 26,941 controls.

Medical cannabis was dispensed in various forms and could be inhaled or taken as an oromucosal spray, oral solution, tablet, or capsule. The products contained only THC (47%), a mix of THC and CBD (29%), or only CBD (24%).

Be aware and look out for any new symptoms immediately following this medication. Anders Holt

Most of the arrhythmias that developed within 180 days were atrial fibrillation or flutter, both in patients who received medical cannabis (76%) and in those who did not (79%). In the cannabis group, 12% of arrhythmias were paroxysmal tachycardias and 12% were “other.” In the control group, 14% of arrhythmias were conduction disorders and 7% were “other.”

The greater risk of new-onset arrhythmias within 180 days in the medical cannabis group worked out to a risk ratio (RR) of 2.07 (95% CI 1.34-2.80). This declined to 1.36 (95% CI 1.00-1.73) by 1 year.

At 180 days of follow-up, cannabis users did not have significantly greater risks of acute coronary syndromes (RR 1.20; 95% CI 0.35-2.04), stroke (RR 0.99; 95% CI 0.55-1.43), or heart failure (RR 0.63; 95% CI 0.26-0.99). It could be that medical cannabis truly doesn’t influence these outcomes or that follow-up wasn’t long enough to detect an effect, Holt speculated, adding that additional studies with larger numbers of cannabis users and longer follow-up will be needed to sort that out.

Remain Vigilant

The study provides a unique perspective on the cardiovascular safety of pot when compared with prior research, which primarily has focused on recreational use of smoked marijuana containing lower concentrations of THC and CBD than what are found in some newer preparations, including edibles, Page said. Previous analyses also have involved mostly chronic cannabis users, which contrasts with the population of new users studied here.

However, there are some limitations, he said. He pointed, for instance, to the lack of information on cigarette smoking, which muddies interpretation of the CV risks of cannabis.

I don’t like to wave my hands in the air and say the sky is falling, but actually the general public should realize that this is a signal and it’s not a good signal. Robert Page II

Nonetheless, these data are important, showing that even in a relatively low-risk population with few cardiovascular comorbidities, medical cannabis may increase the risk of arrhythmias, Page said. “I treat it like a psychotropic medication, to be honest with you, because it carries the same types of side effects,” he added. “I don’t like to wave my hands in the air and say the sky is falling, but actually the general public should realize that this is a signal and it’s not a good signal.”

Many prescription medications have cardiovascular side effects, so what this means is that patients and physicians should be aware of the potential risk when deciding on a treatment for chronic pain and remain vigilant for any signs of arrhythmias if medical cannabis is started, Page said, underscoring that patients need to be honest with their doctors about what they’re taking should problems arise.

The potential risk of new-onset arrhythmia needs to be put into context, Holt said. The absolute risk difference observed equates to a number needed to harm of more than 200, and whether that’s acceptable depends on what it’s being compared to, he said, noting that other medications used to treat chronic pain—opioids, for instance—come with cardiovascular side effects of their own.

Still, Holt said, “I think it’s important to keep in mind that there might be this increased risk of arrhythmias.”