By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
A nationwide Danish study of new prescriptions for medical cannabis for chronic pain compared to control patients has found that the 180-day incidence of atrial fibrillation/flutter is two-fold higher, but the absolute number of arrhythmias is small.
Holt A, Nouhravesh N, Strange JE, et al. Cannabis for chronic pain: Cardiovascular safety in a nationwide Danish study. Eur Heart J 2024;45:475-484
Recreational use of cannabis has been associated with tachycardia, hypotension, arrhythmias, and even acute coronary syndromes (ACS), but little is known about the safety of medical use for chronic pain. Thus, Holt et al used Danish nationwide registers to assess the association between the medical use of cannabis and new-onset arrhythmias. Between 2018 and 2021, the Danish health authorities conducted a trial of prescribing cannabis products containing cannabidiol (CBD) and tetrahydrocannabinol (THC) for patients with chronic pain. They excluded patients with prior cannabis use or documented arrhythmias. Each patient was matched to five control patients diagnosed with chronic pain on the same day and having the same age, sex, chronic pain diagnosis, and use of other pain medications. The primary outcome was new-onset arrhythmias or conduction disorders.
Patients were followed for 180 days or until death or the end of 2021. Secondary outcomes included ACS, syncope, ectopy, stroke, heart failure, or 365 days of follow-up. Out of almost 2 million patients diagnosed with chronic pain during the study period, 5,391 (mean age 59 years, 63% women) were treated with cannabis (47% THC, 24% CBD, and 29% both). There were 26,941 controls. Within 180 days, arrhythmias were observed in 42 cannabis patients and 107 controls. The risk of arrhythmias was higher in the cannabis patients (risk ratio [RR], 2.07; 95% confidence interval [CI], 1.34-2.80). The risk of ACS was not significantly different (RR, 1.2; 95% CI, 0.35-2.04) nor was stroke (RR, 0.99) or heart failure (RR, 0.63).
Among the cannabis patients who developed arrhythmias, 79% had atrial fibrillation/flutter, 14% had conduction disorders, and 7% had other arrhythmias. Patients with cancer and cardiometabolic disease exhibited the highest risk of arrhythmias with cannabis use. The authors concluded that the medical use of cannabis in patients with chronic pain was associated with a higher risk of new-onset arrhythmias.
COMMENTARY
Most cardiologists have seen patients in whom the recreational use of cannabis was associated with arrhythmias. There are reports of almost every acute cardiovascular event related to recreational cannabis use. Studies have shown that it stimulates the sympathetic nervous system and inhibits the parasympathetic system. Thus, these observations are not surprising.
Now that it has been legalized for medicinal purposes in many states, there is concern about these potential adverse effects with medical cannabis. It is prescribed most frequently for chronic pain because of its central nervous system effects. Thus, this nationwide study from Denmark of medical cannabis use for chronic pain syndromes is of interest. The authors showed that the risk of arrhythmias compared to control subjects was two-fold higher with cannabis use. However, the absolute number of arrhythmias was small (0.77% in 180 days of use). Most of the arrhythmias were atrial fibrillation/flutter. Reassuringly, the risk of ACS, stroke, or heart failure was not increased. On the other hand, this was a relatively young group of patients with a low incidence of comorbidities.
There are limitations to this study. Not all the patients obtained a refill of the initial prescription. This may be because it was ineffective, because of ordinary nonadherence, or the result of adverse effects. Interestingly, in those who did refill their prescription, there was no difference in the results. This could mean that the adverse effects of medical cannabis are transient or an early effect of initial use.
The study included all delivery methods (inhalation, oral spray, oral solution, and pills), but the route of administration for each patient was not known to the investigators. Finally, the dose of the active ingredients in medical cannabis probably is lower than in recreational cannabis products, especially since the newer synthetic cannabinoids encountered in recreational cannabis are much more potent than those found in pure marijuana products.
The strengths of the study include that it was a large, nationwide database, which should reduce any inclusion bias. In addition, the patients were well matched to five control subjects. Thus, clinicians and patients need to be aware that medical cannabis use in any form may have cardiovascular adverse effects, especially atrial fibrillation/flutter.
