Inverse correlation between plasma 2‐arachidonoylglycerol levels and subjective severity of depression

Abstract

Objective Endocannabinoids have been implicated in the pathophysiology of Major Depressive Disorder (MDD) and might represent potential targets for therapeutic intervention. Objectives of the study were: (1) to measure plasma levels of endocannabinoids in a group of antidepressant‐free depressed outpatients; (2) to explore their relationship with the severity of depressive symptoms as subjectively perceived by the patients; and (3) to investigate the effect of the selective serotonin reuptake inhibitor escitalopram on endocannabinoid levels. Methods We measured plasma levels of the two major endocannabinoids, 2‐arachidonoylglycerol (2‐AG) and N‐arachidonoylethanolamine (anadamide), in 12 drug‐free outpatients diagnosed with MDD and in 12 matched healthy controls. In the patient group, endocannabinoids plasma levels were assessed at baseline and after 2 months of treatment with escitalopram. Results Baseline plasma levels of the two endocannabinoids did not differ between depressed patients and healthy controls. However, there was a significant inverse correlation between 2‐arachidonoylglycerol levels and the severity of subjectively perceived depressive symptoms. Treatment with escitalopram did not change endocannabinoid levels in depressed patients, although it caused the expected improvement of depressive symptoms. Conclusions Our results suggest that 2‐arachidonylglycerol, the most abundant endocannabinoid in the central nervous system, might act to mitigate depressive symptoms, and raise the interesting possibility that 2‐arachidonylglycerol and anandamide are differentially regulated in patients affected by MDD. Also, our data suggest but do not prove that the endocannabinoid system is not regulated by serotonergic transmission, at least in depressed patients.

Commonalities for comorbidity: Overlapping features of the endocannabinoid system in depression and epilepsy

“…2-AG is largely understudied in epilepsy, with one study of absence seizures in Genetic Absence Epilepsy Rat from Strasbourg (GAERS) reporting an increase in 2-AG ( 34 ) and another study in patients with MTLE reporting a decrease ( 27 ). Taken together, it seems that 2-AG may be involved in depression- and epilepsy-comorbidity, though it should also be noted that several studies of each condition showed no changes in 2-AG levels [for example, ( 28 , 35 , 36 )]. Agents that increase 2-AG may be helpful for depression, but much more work is needed to assess their safety and/or efficacy as a treatment strategy in epilepsy.…”

2-Arachidonoylglycerol Synthesis: Facile and Handy Enzymatic Method That Allows to Avoid Isomerization

“…The modulation of circulating or tissue EC and NAEs levels produces changes in cannabinoid receptor activation that acts to re-establish the homeostasis of other mediators, such as γ-aminobutyric acid and glutamate, and to restore the cell to its original steady-state condition [2]. Due to the prominent role of these signaling molecules, the literature reports numerous biochemical studies on the EC and NAEs levels associated with pathological conditions [3][4][5][6][7] or on the modification of the endocannabinoid system activity in cellular [8][9][10] or animal [11,12] pathological models. Moreover, the literature reports different LC or GC-MS methods that quantify EC and NAEs to study and understand their role in pathological processes and homeostasis restoration [3,7,13].…”

Role of cardiorespiratory fitness on the associations between endocannabinoid system and depressive symptoms in adults diagnosed with depression: the SONRIE study

“…11 Specifically, the scientific literature reported lower endocannabinoids serum concentrations, such as anandamide (AEA) and 2-arachinodoil glycerol (2-AG), in patients with depression. [12][13][14][15] Several studies found that physical exercise could increase endocannabinoids serum concentrations as an acute response. [16][17][18][19][20] However, there is no evidence if having a good physical fitness, expressed by cardiorespiratory fitness (CRF), could be an interacting factor in the relationships between ES concentrations and depressive symptoms.…”