Reviewing the Role of the Endocannabinoid System in the Pathophysiology of Depression

Abstract

Major depressive disorder is a high-impact, debilitating disease and it is currently considered the most prevalent mental illness. It is associated with disability, as well as increased morbidity and mortality. Despite its significant repercussions in our society, its exact pathophysiology remains unclear and therefore, available antidepressant treatment options are limited and, in some cases, ineffective. In the past years, research has focused on the development of a multifactorial theory of depression. Simultaneously, evidence supporting the role of the endocannabinoid system in the neurobiology of neuropsychiatric diseases has emerged. Studies have shown that the endocannabinoid system strongly impacts neurotransmission, and the neuroendocrine and neuroimmune systems, which are known to be dysfunctional in depressive patients. Accordingly, common antidepressants were shown to have a direct impact on the expression of cannabinoid receptors throughout the brain. Therefore, the relationship between the endocannabinoid system and major depressive disorder is worth consideration. Nevertheless, most studies focus on smaller pieces of what is undoubtedly a larger mosaic of interdependent processes. Therefore, the present review summarizes the existing literature regarding the role of the endocannabinoid system in depression aiming to integrate this information into a holistic picture for a better understanding of the relationship between the two.

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

“…The endocannabinoid system (ECS) modulates many physiological processes, including the cardiovascular, gastrointestinal and immune systems, pain, learning, memory, perception, mood, appetite, metabolism, emotions, and sleep [22,112,113,[277][278][279][280][281][282][283][284][285]. The bioactive endocannabinoid lipid mediators have potent anti-inflammatory activities [286][287][288][289][290][291].…”

Role of the Endocannabinoid System in the Regulation of Intestinal Homeostasis

“…19 It is perhaps best known for playing important roles in food intake and energy metabolism, regulation of the hypothalamic-pituitary-adrenal axis, pain transmission, and a variety of emotional and behavioral conditions. 14,[19][20][21][22][23][24][25] The ECS was discovered after the isolation of D 9 tetrahydrocannabinol (THC) as the major psychoactive constituent of cannabis. 26 This finding led to the development of ligands that were used to identify the receptors for cannabis.…”

Exploration of Multiverse Activities of Endocannabinoids in Biological Systems

“…Several studies performed to date have established the presence of depressive symptoms under lower concentrations of endocannabinoids, and anti-depressant effects upon higher levels of endocannabinoids, supporting the evident role of endocannabinoids in management of depression. The hypothesis supporting this activity is the considerable neurogenic effects produced by endocannabinoids since the process of neurogenesis is downregulated in depressive patients [ 108 , 109 , 110 ]. Upon activation, the CB1 receptors induce proliferation of progenitor cells and endorse neurogenesis.…”