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.
Highlights
Major Depressive Disorder (MDD) is the most common mood disorder characterized by the loss of interest or pleasure in activities, unjustified feelings of worthlessness and presence of depressed mood or aversion to activity (American Psychiatric Association, 2013).According to the World Health Organization, each year, 25% of the European population suffers from anxiety or depressive disorders (World Health Organization, 2020)
The association of endocannabinoid receptors to MDD is not sufficient to explain the entirety of its pathophysiology
Given the intricacy of the mechanisms underlying stress-related conditions, further studies are essential to evaluate the role of different players, such as transient receptor potential vanilloid 1 (TRPV1) receptors and other G-protein coupled receptor (GPCR); diverse neuronal subpopulations, i.e., GABAergic vs glutamatergic; and even considering brain regions, which could interact with each other to regulate mood and cognitive aspects involved in MDD
Summary
Major Depressive Disorder (MDD) is the most common mood disorder characterized by the loss of interest or pleasure in activities, unjustified feelings of worthlessness and presence of depressed mood or aversion to activity (American Psychiatric Association, 2013). It was observed that chronic stress induced a reduction of AEA levels in the amygdala and hippocampus (Patel et al, 2005; Wang et al, 2012) via increased activity of FAAH (Navarria et al, 2014; Gray et al, 2015), which is consistent with previous evidence supporting the anxiolytic properties of AEA (Patel and Hillard, 2006) This reduction was attributed to the elevated serum corticosterone content (Hill et al, 2009) through a CRHR1mediated mechanism (Gray et al, 2016) resulting in the generation of anxiety (Gray et al, 2015).
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