This chapter aims at exploring the use and misuse of cannabinoids as it has become a major societal issue. In the first section, we describe the historical use of cannabis as a natural cure in ancient civilizations. We then explore the current use of cannabinoids in medicine, which includes innovative strategies for treating various diseases such as multiple sclerosis or cancer-induced pain. In the second section, we consider how the discovery and characterization of the endocannabinoid system have increased knowledge of this system's mode of action. Consumption of cannabis for recreational use however is a significant public health issue today. Scientific advances are confronted with the adverse health effects that are demonstrated in preclinical and clinical studies based on the psychotic and addictive properties of this compound. In the third section, we therefore provide an overview of the recent findings on the endocannabinoid system using animal models with proposed molecular mechanisms and potential interactions with other neuromodulatory systems like the opioid system. Finally, through alternative strategies to current treatments with both phyto-and synthetic cannabinoids, we try to reconcile the beneficial aspects of the use of cannabinoids for medication and the aspects associated with addictive properties.