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

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.

[The endocannabinoid system and its possible role in neurobiology of psychiatric disorders]. / Il sistema endocannabinoide e il suo possibile ruolo nella neurobiologia dei disturbi psichiatrici.

In the last years, numerous researches led to identify endocannabinoid system, a sophisticated short-range signaling system which is located both in Central Nervous System (CNS) and in whole organism. Because of its flexibility of expression, it plays a modulatory role in controlling the answers to stimuli which disturb homeostasis. On one hand it lets them occur whilst on the other it limits them in order to protect organism from consequences due to excessive reaction. In the CNS, endocannabinoid system is able to control the release of several neurotransmitters thanks to its retrograde signaling, modulating synaptic activity. Analysing this property during preclinical studies, it came out that the endocannabinoid system is involved in numerous physiologic processes, such as neuroendocrine axes, food consumption, brain reward and satisfaction mechanisms, memories storing and extinction, emotions and neurodevelopment regulation. Such discoveries have led researchers to suppose and investigate an alteration of this system in the physiopathology of some psychiatric disorders such as anxiety disorder, depression, eating disorders, addiction and schizophrenia. Results of such studies on animal models show a possible involvement of this system and were quickly followed by clinical studies which seem to confirm it. These findings might open new scenarios for understanding the pathogenesis of several psychiatric disorders and, at same time, they show new prospects for their treatment.