Oral Cannabidiol in Inflammatory Myo-Pericardial Diseases: A Systematic Review of Myo-Pericardial Recovery, Inflammation, Clinical Outcomes, and Safety

Abstract

Background: Inflammatory myo-pericardial syndromes, including myocarditis, myopericarditis, peri-myocarditis, and inflammatory cardiomyopathy, are associated with myo-pericardial injury, ventricular dysfunction, arrhythmia, and adverse long-term remodeling. Despite advances in cardiac magnetic resonance (CMR)-based diagnosis and risk stratification, therapeutic options targeting myo-pericardial inflammation remain limited. Cannabidiol (CBD), a non-intoxicating Phyto-cannabinoid with anti-inflammatory, antioxidant, and potential immunomodulatory properties, has emerged as a candidate therapy for inflammatory cardiac disease. This systematic review evaluated the efficacy, safety, and potential effects of oral CBD on myo-pericardial recovery in adults with inflammatory myo-pericardial syndromes.

Methods: A systematic review was conducted in accordance with PRISMA 2020. PubMed/MEDLINE, Embase, Scopus and Web of Science were searched from inception through 2026. Eligible studies included adults with acute or chronic myocarditis, myopericarditis, peri-myocarditis, or inflammatory cardiomyopathy receiving oral CBD, including pharmaceutical-grade formulations. Randomized controlled trials and relevant prospective or retrospective clinical studies were eligible. Outcomes included CMR measures of myo-pericardial recovery, cardiac function and remodeling, inflammatory markers, clinical outcomes, and adverse events.

Results: Clinical evidence available consisted of the Phase II ARCHER trial, in which 109 acute myocarditis patients were randomized to oral CBD (n=56) or placebo (n=53). CBD had no significant effect on myo-pericardial extracellular volume or global longitudinal strain but significantly decreased left ventricular mass (mean difference −9.23 g; 95% CI −16.36 to −2.11; P=0.0117) and left atrial end-systolic volume (mean difference −8.09 mL; P=0.0376). Experimental studies showed decreased pericardial effusion, increased pericardial thickness, and decreased inflammatory signals in the pericardium; and the Phase II MAvERIC-Pilot trial in 27 patients with recurrent pericarditis showed that CBD decreased pain and normalized CRP in patients with elevated baseline CRP, with 80% remaining recurrence-free at the time of extension follow-up. In general, there were suggestive beneficial effects of CBD on myo-pericardial remodeling and pericardial inflammation, but evidence for definite clinical efficacy is lacking.

Conclusions: Current evidence does not demonstrate a statistically significant benefit of oral cannabidiol on the primary measures of myo-pericardial recovery, specifically CMR-derived extracellular volume and global longitudinal strain, in mild-to-moderate acute myocarditis. Nevertheless, favorable changes in selected measures of cardiac remodeling and supportive mechanistic evidence suggest a potential therapeutic role that warrants further investigation. The evidence base remains limited to a small number of studies, and larger, adequately powered trials with longer follow-up, phenotype-specific assessment, and clinically meaningful outcomes are required before oral cannabidiol can be considered part of routine treatment for inflammatory myo-pericardial syndromes.