A recent clinical investigation presented at Heart Failure 2025, the premier scientific congress held by the European Society of Cardiology, has brought to light promising findings regarding the safety of a pharmaceutically manufactured cannabidiol formulation in patients with increased cardiovascular risk. This study, conducted within a rigorous placebo-controlled framework, evaluated both the general safety and, critically, the cardiac safety profile of cannabidiol, a non-psychoactive component derived from Cannabis sativa.
The spectrum of inflammatory diseases affecting cardiac tissues, such as myocarditis and pericarditis, currently suffers from a substantial lack of effective treatment options. These conditions, characterized respectively by inflammation of the heart muscle and the surrounding pericardial sac, contribute significantly to the burden of heart failure and other progressive cardiovascular morbidities. Notably, cannabidiol has drawn substantial attention for its molecular capacity to modulate intracellular inflammatory processes, particularly its inhibitory effect on the inflammasome pathway, a key driver in the pathogenesis of these cardiac inflammations.
Principal Investigator Dr. Leslie Cooper from the Mayo Clinic, Jacksonville, Florida, articulated the foundational rationale for the trial. Patients with pre-existing cardiovascular disease or risk factors hospitalized during the COVID-19 pandemic were identified as a vulnerable cohort with heightened risk for cardiac inflammation. The investigation sought to determine whether orally administered GMP-grade cannabidiol, titrated up to 7.5 mg/kg twice daily or the maximum tolerated dose, could demonstrate safety and potential efficacy in this demographic.
The study enrolled 89 adult subjects who experienced non-critical COVID-19 hospitalization and possessed previous CVD history or risk factors. Randomization evenly distributed participants between the cannabidiol treatment arm and placebo control. The primary endpoint focused explicitly on safety parameters over a 60-day period post-randomization, scrutinizing the incidence of adverse events and serious adverse events meticulously reported by clinical investigators.
However, due in part to the waning incidence of eligible COVID-19 cases toward the latter stages of the pandemic, the trial concluded prematurely, limiting the final cohort to less than the originally planned enrollment. Despite this limitation, the comprehensive safety analysis revealed no significant difference between the cannabidiol group and placebo in the frequency of treatment-related adverse events, which hovered around 24.4% and 22.7%, respectively. Serious adverse events were similarly comparable, with rates of 11.1% in the cannabidiol group versus 9.1% in placebo.
Importantly, mortality was absent in the cannabidiol cohort, with two deaths recorded in the placebo group attributed to respiratory failure rather than cardiac causes. This observation provides a crucial piece of evidence supporting the safety profile of cannabidiol, especially in the context of cardiac and pulmonary vulnerability in COVID-19 patients.
The detailed assessment of specific adverse event categories further underscored the safety findings. Gastrointestinal disorders, nervous system disturbances, and respiratory or thoracic complaints manifested at comparable rates across both arms, indicating no emergent safety concerns linked specifically to the investigational compound. This is particularly noteworthy considering the systemic nature of cannabidiol’s pharmacodynamics.
In light of cardiac safety, a paramount concern in cardiovascular pharmacotherapy, the frequencies of cardiac disorders reported were identical in both groups, each accounting for 9% of participants. Electrocardiogram monitoring revealed a lone instance of mild QTc interval prolongation in the cannabidiol group, but overall mean QTc values showed minimal deviation from baseline at day 28, affirming negligible proarrhythmic risk.
Dr. Cooper emphasized that these findings robustly suggest that GMP-cannabidiol is well tolerated by patients at elevated cardiovascular risk and crucially does not increase the frequency or severity of cardiac side effects compared with placebo. She pointed to ongoing and upcoming phase II and III clinical trials—ARCHER and MAVERIC, respectively—that aim to elucidate the therapeutic potential of cannabidiol in acute myocarditis and recurrent pericarditis, heralding a new frontier in cardiology.
Scientific interest in cannabidiol has surged not only due to its immunomodulatory properties but also because it lacks the psychotropic effects that complicate the use of cannabis-derived compounds in clinical settings. Its mechanism of action appears to hinge on the attenuation of inflammasome activation, a process intimately tied to maladaptive cardiac inflammation and fibrosis, which ultimately fuels heart failure progression.
This early-phase investigation thus provides a critical foundation for larger, more definitive trials. The absence of notable adverse cardiac events in a high-risk population lends credence to the safety framework upon which future efficacy studies will build. Cardiovascular researchers and clinicians alike anticipate that cannabidiol, with its distinctive pharmacological profile, may emerge as a viable adjunct or alternative in the management of inflammatory cardiomyopathies.
The trial’s pharmaceutical-grade cannabidiol formulation was administered under stringent Good Manufacturing Practice conditions, ensuring dosing precision and product consistency—an essential component when translating cannabinoid therapies from bench to bedside. The rigorous methodological approach, including randomized placebo control and ECG monitoring, reinforces the validity and generalizability of the findings within cardiology practice.
Furthermore, the study’s context within the COVID-19 pandemic underscores the complexity and unmet needs in treating cardiac complications arising from viral infections. The observed safety in this fragile patient subset offers hope for addressing myocarditis and pericarditis following infectious triggers, a scenario that has become increasingly relevant in post-pandemic clinical care pathways.
In conclusion, while definitive efficacy conclusions remain pending due to recruitment limitations, the cardiac safety profile and tolerability of pharmaceutically manufactured cannabidiol in cardiovascularly at-risk patients was reassuring. Continued research efforts spearheaded by forthcoming clinical trials will determine whether this non-psychoactive cannabinoid can be integrated into standard cardiovascular anti-inflammatory therapy, potentially revolutionizing treatment paradigms for myocarditis, pericarditis, and possibly chronic heart failure.
Subject of Research: Cardiac safety evaluation of pharmaceutically manufactured cannabidiol in patients with increased cardiovascular risk hospitalized for COVID-19
Article Title: Cardiac safety of pharmaceutically manufactured cannabidiol in patients at increased cardiovascular risk
News Publication Date: 17 May 2025
Web References:
- https://esc365.escardio.org/Heart-Failure/sessions/14884-eposters-in-myocardial-disease-1
- https://clinicaltrials.gov/study/NCT05180240
- https://clinicaltrials.gov/study/NCT06708299
References:
- Martinez Naya N, Kelly J, Corna G, et al. Molecular and cellular mechanisms of action of cannabidiol. Molecules. 2023;28:5980.
- McNamara D, Cooper LT, Arbel A, et al. Impact of cannabidiol on myocardial recovery in patients with acute myocarditis: Rationale & design of the ARCHER trial. ESC Heart Fail. 2024;11:3416–3424.
Keywords: Health care, Cardiology, Cannabidiol, Myocarditis, Pericarditis, Cardiac inflammation, COVID-19, Cardiovascular safety, Heart failure, Clinical trial, Pharmacology, Inflammasome
