Cannabis sativa L., commonly known as hemp, has been cultivated and utilized medically throughout the world. Humans and other mammals contain an Endocannabinoid system (ECS) within their bodies, which plays a significant role in maintaining homeostasis, or balance, in the body. Together with the CB1 and CB2 receptors, constitute the ECS, a complex and highly conserved neuromodulator network involved in regulating a wide array of physiological processes. Cannabidiol (CBD) and other phytocannabinoids are gaining attention for their therapeutic potential in cardiovascular disease (CVD), the world’s leading cause of death. Heart failure (HF) is characterized by energy deprivation, calcium (Ca 2+) handling alterations, and inflammation: effects associated with mitochondrial dysfunction. One of the recent studies by García-Rivas et al., (2025) demonstrated that cannabidiol (CBD) offers cardio protection in a heart failure mouse model induced by L-NAME and ANGII administration. CB2 has emerged as a modulator of cardiovascular health, exerting potent anti-inflammatory and the protective effects while avoiding the psychotropic activity associated with CB1 activation. However, cannabinoids have not yet reached clinical maturity for broad implementation in cardiovascular therapeutics. One of the most pressing issues is the translational gap between experimental findings and clinical application.