A pharmaceutically manufactured cannabidiol (CBD) formulation has demonstrated a favorable cardiac safety profile in patients with cardiovascular risk factors, according to research presented at the European Society of Cardiology's Heart Failure 2025 congress in Belgrade, Serbia.
The study comes at a critical time when treatment options for inflammatory heart conditions such as myocarditis and pericarditis remain limited. Cannabidiol, which lacks the psychotropic effects of cannabis, has shown promise in preclinical studies by inhibiting the inflammasome pathway—a key cellular process involved in cardiac inflammation.
"We knew that patients with cardiovascular disease or risk factors who were hospitalized for COVID-19 infection may be at high risk of cardiac inflammation," explained Dr. Leslie Cooper, Co-Principal Investigator from the Mayo Clinic in Jacksonville, Florida. "We conducted a placebo-controlled trial of an oral pharmaceutically manufactured cannabidiol formulation to assess its efficacy and safety."
Trial Design and Patient Population
The prospective, randomized, placebo-controlled trial enrolled adult patients with either established cardiovascular disease or at least one major cardiovascular risk factor who had been hospitalized for non-critical COVID-19 infection. Participants received either Good Manufacturing Practice (GMP)-cannabidiol titrated up to 7.5 mg/kg twice daily (or maximum tolerated dose) or placebo.
Although the trial was terminated early due to declining COVID-19 cases, the safety analysis included 89 patients with a mean age of 61 years, with 43% being female. Of these, 45 patients received GMP-cannabidiol and 44 received placebo.
Safety Outcomes Show Comparable Profiles
The primary safety endpoint examined serious adverse events (SAEs) and adverse events (AEs) during the 60 days following randomization. Results showed similar safety profiles between the treatment groups:
- Treatment-related adverse events: 24.4% with GMP-cannabidiol vs. 22.7% with placebo
- Serious adverse events: 11.1% with GMP-cannabidiol vs. 9.1% with placebo
- No deaths occurred in the GMP-cannabidiol group, while two deaths due to respiratory failure were reported in the placebo group
Common adverse events were distributed similarly between groups:
- Gastrointestinal disorders: 22.2% with GMP-cannabidiol vs. 20.5% with placebo
- Nervous system disorders: 17.8% with GMP-cannabidiol vs. 18.2% with placebo
- Respiratory, thoracic, and mediastinal disorders: 11.1% with GMP-cannabidiol vs. 9.1% with placebo
Cardiac Safety Findings
Particularly noteworthy were the cardiovascular safety findings, a critical consideration for any therapy targeting cardiac conditions. Cardiac disorders were reported in exactly 9% of patients in both the GMP-cannabidiol and placebo groups.
Only one patient (2%) in the GMP-cannabidiol group developed mild QTc prolongation detected by electrocardiogram (ECG). Overall, changes in ECG measurements were minimal, with similar mean QTc values from baseline to day 28 in the GMP-cannabidiol group (425 msec and 418 msec, respectively) and in the placebo group (418 msec and 419 msec, respectively).
Implications for Future Research
"GMP-cannabidiol was well tolerated overall and most importantly, the rate of cardiac side effects was low and similar compared with placebo," Dr. Cooper summarized. "These safety data are encouraging as two larger trials assessing efficacy and safety are underway with GMP-cannabidiol."
The phase II ARCHER trial investigating cannabidiol in patients with acute myocarditis is expected to report results later in 2025, while findings from the phase III MAVERIC trial in patients with recurrent pericarditis are anticipated in 2026.
Cannabidiol's Potential Mechanism in Cardiac Inflammation
Cannabidiol has gained scientific interest for its immunomodulatory properties without the psychotropic effects that complicate the use of other cannabis-derived compounds. Its mechanism appears to involve attenuating inflammasome activation, a process linked to maladaptive cardiac inflammation and fibrosis that contributes to heart failure progression.
The inflammasome pathway has been identified as a key driver in the development and progression of myocarditis, pericarditis, and heart failure. By targeting this pathway, cannabidiol may offer a novel approach to managing inflammatory heart conditions that currently have few effective treatment options.
Significance in Post-Pandemic Cardiology
The study's context within the COVID-19 pandemic highlights the complexity and unmet needs in treating cardiac complications arising from viral infections. The observed safety in this vulnerable patient population offers hope for addressing myocarditis and pericarditis following infectious triggers, a scenario that has become increasingly relevant in post-pandemic clinical care.
While the trial was unable to fully assess efficacy due to early termination, the favorable safety profile provides a foundation for ongoing and future studies. If proven effective in larger trials, pharmaceutical-grade cannabidiol could potentially revolutionize treatment approaches for inflammatory cardiac conditions, offering a new option for patients with limited therapeutic alternatives.
As the medical community awaits results from the ARCHER and MAVERIC trials, this safety study represents an important step forward in exploring cannabidiol's potential role in cardiovascular medicine.
