Abstract Importance Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms. Objective To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19. Design, Setting, and Participants This prospective open-label single-site randomized clinical trial used a 1:1 block randomization design to examine emotional exhaustion and burnout symptoms among frontline health care professionals (physicians, nurses, and physical therapists) working with patients with...