Medical cannabis use for the management of chronic pain is associated with an increased risk of new-onset arrhythmia, a Danish registry study has shown.

While the absolute risk difference remained low, the investigators flagged the need for caution and more research due to the increasing legalisation and use of medical cannabis worldwide.

The study, published in the European Heart Journal [link here], compared cardiovascular outcomes in 5,391 adults with chronic pain and a new claimed prescription for medical cannabis and 26,941 matched controls with a chronic pain diagnosis using other pain medication.

Medicinal cannabis included products containing either tetrahydrocannabinol (THC) or cannabidiol (CBD) or both in equal amounts (THC/CBD). The study period was 2018-2021 following the launch of Denmark’s trial program of prescribed medical cannabis for chronic pain on January 1, 2018.

Patients had a median age of 59 years and included those with musculoskeletal (46%), neurological (13%), cancer (11%), or unspecified pain (30%).

The study found double the risk of new-onset arrhythmia in patients exposed to medical cannabis compared to non-exposed patients within 180 days of follow-up (0.8% v 0.4%; aRR 2.07).

Most events in the cannabis-exposed group were atrial fibrillation/flutter (76%), followed by paroxysmal tachycardias (12%), and other arrhythmias (12%).

The association between medical cannabis use and new-onset arrhythmia was consistently similar across prespecified subgroups based on age, sex and cannabis product type.

High risk groups

“Patients with known cardiometabolic disease and patients with cancer were the subgroups associated with the highest absolute risk differences, which could reflect an elevated susceptibility to the proposed side effects of medical cannabis use,” the study authors said.

In supplementary analyses, there was no difference in the risk of acute coronary syndrome between cannabis-exposed and non-exposed patients (aRR 1.20) and no significant associations with risk of first-time stroke or heart failure.

“However, these findings should be explored further as larger sample sizes or longer follow-ups could yield different results—especially since the most common arrhythmia observed, atrial fibrillation, is closely linked to the risk of acute coronary syndrome, stroke, and heart failure.”

The study authors said cardiovascular side effects following recreational cannabis use have been described previously.

“Activating the endocannabinoid system through receptors CB1 and CB2, THC and CBD have been related to arrhythmia through induction of the sympathetic nervous system, inhibition of the parasympathetic nervous system, and interaction with ion channels involved in the cardiac conduction system,” they wrote.

The investigators noted their study population had a low age and low prevalence of comorbidity but that “growing acceptance and availability of medical cannabis treatment will lead to increased use among patient groups with inherently greater risk of arrhythmia.”

“If corroborated in future, randomised studies, previously unknown associations between the risk of new-onset arrhythmia and medical cannabis use should motivate improved vigilance regarding medical cannabis use—particularly with medical cannabis as pain treatment still being debated.”

They concluded that the elevated risk of new-onset arrhythmia with cannabis use was “vital knowledge for any prescribing physician due to the rising demand for medical cannabis as pain treatment.”

An accompanying editorial in the journal [link here] emphasised the finding that the highest absolute risk differences were observed in people with cardiometabolic disease and cancer.

“Therapeutically, these findings suggest that medical cannabis may not be a ‘one-size-fits-all’ therapeutic option for certain medical conditions and should be contextualised based on patient comorbidities and potential vulnerability to side effects,” it said.

The authors also noted that the finding of no increased risk of ACS with cannabis exposure was inconsistent with other observational studies.

For example, a 2021 US study [link here] of 33,173 young adults (18-44 years of age) found recent cannabis use associated with double the risk of MI (aOR 2.07). The risk was further increased in more frequent users of cannabis (>4 times per month; aOR 2.31).

They said the term medical or medicinal cannabis implied that “…the product may have some clinical monitoring along with safety and efficacy data, which is far from true with cannabis.”

In conclusion, the editorial commended the study findings which “highlight and add to the growing evidence that as with all psychotropic agents, adverse effects, particularly CV, can occur with cannabis.”