Key take-aways
- Cannabidiol – which lacks the psychotropic effects of cannabis – has been shown to have beneficial effects on inflammation in myocarditis and pericarditis models.
- A prospective placebo-controlled trial was conducted with an oral pharmaceutically manufactured (GMP) cannabidiol formulation in patients at high risk of cardiovascular events who were hospitalised for non-critical COVID-19 infection.
- GMP-cannabidiol formulation was well tolerated with a similar low rate of overall and cardiac side effects as placebo, supporting its study in further trials.
Belgrade, Serbia – 17 May 2025. A pharmaceutically produced cannabidiol formulation had a good overall safety profile, including cardiac safety, according to research presented today at Heart Failure 2025,1 a scientific congress of the European Society of Cardiology (ESC).
Currently, there are limited treatment options for inflammatory conditions of the heart, such as myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the membrane surrounding the heart). Cannabidiol – which lacks the psychotropic effects of cannabis – has been shown to inhibit activation of the inflammasome pathway,2 an intracellular process known to be involved in the development and progression of myocarditis, pericarditis and heart failure.
Explaining the rationale for the current trial, Co-Principal Investigator, Dr. Leslie Cooper from the Mayo Clinic, Jacksonville, Florida, USA, said: "We knew that patients with cardiovascular disease (CVD) or CVD risk factors who were hospitalised for COVID-19 infection may be at high risk of cardiac inflammation. We conducted a placebo-controlled trial of an oral pharmaceutically manufactured (GMP) cannabidiol formulation to assess its efficacy and safety. The pandemic ended before we had recruited sufficient participants to analyse whether GMP-cannabidiol had a positive effect on the primary efficacy endpoint but we thought that the lack of safety signals was important data to share."
This prospective trial included adult patients with a prior history of CVD and/or at least one major risk factor for CVD who had been hospitalised for non-critical COVID-19 infection. Participants were randomised to either GMP-cannabidiol titrated up to 7.5 mg/kg twice daily (or maximum tolerated dose) or placebo. The primary safety endpoint was the number of serious adverse events (SAEs) and adverse events (AEs) during the 60 days following randomisation.
The trial was terminated early due to a lack of eligible patients with COVID-19 to support full recruitment. The recruited safety population included 89 patients (mean age of 61 years; 43% female): 45 patients received GMP-cannabidiol and 44 received placebo.
Overall safety was similar between the groups. The frequency of investigator-assessed treatment-related AEs was 24.4% with GMP-cannabidiol and 22.7% with placebo. The frequency of SAEs was 11.1% with GMP-cannabidiol and 9.1% with placebo. There were 0 deaths in the GMP-cannabidiol group and 2 deaths in the placebo group, both due to respiratory failure.
There were no significant differences between groups in the most common AEs of gastrointestinal disorders (GMP-cannabidiol: 22.2%; placebo: 20.5%); nervous system disorders (GMP-cannabidiol: 17.8%, placebo: 18.2%); and respiratory, thoracic and mediastinal disorders (GMP-cannabidiol: 11.1%, placebo: 9.1%).
Of note, the cardiovascular safety profile of GMP-cannabidiol appeared similar to that of placebo. Cardiac disorders were reported in 4 patients (9%) in both the GMP-cannabidiol group and the placebo group. One patient (2%) in the GMP-cannabidiol group developed mild QTc prolongation detected by electrocardiogram (ECG). However, 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).
Summarising the findings, Dr. Cooper said: "GMP-cannabidiol was well tolerated overall and most importantly, the rate of cardiac side effects was low and similar compared with placebo. These safety data are encouraging as two larger trials assessing efficacy and safety are underway with GMP-cannabidiol. The phase II ARCHER trial3 in patients with acute myocarditis is expected to report later in 2025, while results from the phase III MAVERIC trial4 in patients with recurrent pericarditis are expected in 2026."
