ABSTRACT
For centuries, different cultures around the world have used the herb Cannabis sativa for its therapeutic and mood-elevating properties. After the discovery and classi˜cation of the endocannabinoid system in the early 1990s, a growing body of research has unequivocally demonstrated that de˜cits in this neuromodulatory system may result in the pathological development of behavioral, physiological, cognitive, and endocrine symptoms of major depression. The aim of this chapter is to summarize this current state of knowledge regarding the role of the endocannabinoid system in the etiology of major depression, derived from preclinical animal models of depression as well as from genetic, clinical, and postmortem reports in human populations. Furthermore, this review will present research indicating that endocannabinoid signaling is critically involved in the proper functioning of monoamine neural systems, activation and termination of the neuroendocrine stress axis, and a fundamental component of synaptic remodeling and neuroplasticity in the brain-processes that are often impaired in clinically depressed populations. Lastly, evidence will
10.1 Introduction ..........................................................................................................................203 10.2 Endocannabinoid System ......................................................................................................204 10.3 Effects of Exogenous Cannabinoids on Mood and Emotionality .........................................207 10.4 Disruption of Endocannabinoid Signaling and Implications for Emotional Behavior .........207 10.5 Endocannabinoid Signaling in Animal Models of Depression ............................................208
