Impact of cannabidiol on myocardial recovery in patients with acute myocarditis: primary results of the ARCHER study

Introduction: Cannabidiol has been shown to exert significant anti-inflammatory effects and has demonstrated efficacy in murine models of autoimmune myocarditis, pericarditis, and heart failure. The ARCHER Study assessed whether a pharmaceutically produced cannabidiol formulation showed beneficial effects on cardiac magnetic resonance (CMR) endpoints known to predict prognosis in this patient population. Methods: In a multicentre international double-blind placebo-controlled phase 2 study, 109 patients within 10 days of CMR confirmed diagnosis of acute myocarditis were randomly assigned to 12 weeks of pharmaceutically produced oral cannabidiol (active) or placebo. Dose was titrated up to 10 mg/kg of body weight twice daily. Primary endpoints were the difference in extracellular volume (ECV) and global longitudinal strain (GLS) measured by CMR at week 12. Other CMR endpoints included left-ventricular ejection fraction (LVEF), LV mass, intracellular volume (ICV), LV end-diastolic and end-systolic volumes (LVEDV, LVESV), and left-atrial end-systolic volume (LAESV). Results: All randomized patients (56 active/53 placebo) completed the study with no loss to follow-up. Study drug appeared safe and well tolerated. Week 12 mean ECV was 33.6 ml in the active group and 37.3 ml in the placebo group, a difference of -3.7 ml, CI: -7.4 to 0.1; P = .0538; GLS difference was -0.1, CI: -1.2 to 1.1; P = .90. LV mass was significantly reduced in the active group at 121.1 g vs placebo 130.3 g, difference -9.2, CI: -16.4 to -2.1; P = .0117. LAESV was significantly reduced in the active group (-8.1 ml; P = .0376) while the reduction in LVEDV failed to reach significance (-7.4 ml; P = .098). Conclusion: In mild-to-moderate acute myocarditis, treatment with pharmaceutically manufactured cannabidiol was not associated with a statistically significant change in myocardial ECV or GLS, although a trend towards reduction in ECV was observed. A significant reduction in LV mass was seen in the active treatment group. Further investigation is warranted.