“There is no argument with regard to the physical and psychological stress-related nature of neuropsychiatric disorders. Yet, the mechanisms that facilitate disease onset starting from molecular stress responses are elusive.
Environmental stress challenges individuals’ equilibrium, enhancing homeostatic request in the attempt to steer down arousal-instrumental molecular pathways that underlie hypervigilance and anxiety.
A relevant homeostatic pathway is the endocannabinoid system (ECS).
In this review, we summarize recent discoveries unambiguously listing ECS as a stress coping mechanism.
As stress evokes huge excitatory responses in emotional-relevant limbic areas, the ECS limits glutamate release via 2-arachydonilglycerol (2-AG) stress-induced synthesis and retrograde cannabinoid 1 (CB1)-receptor activation at the synapse. However, ECS shows intrinsic vulnerability as 2-AG overstimulation by chronic stress rapidly leads to CB1-receptor desensitization.
In this review, we emphasize the protective role of 2-AG in stress-response termination and stress resiliency. Interestingly, we discuss ECS regulation with a further nuclear homeostatic system whose nature is exquisitely epigenetic, orchestrated by Lysine Specific Demethylase 1.
We here emphasize a remarkable example of stress-coping network where transcriptional homeostasis subserves synaptic and behavioral adaptation, aiming at reducing psychiatric effects of traumatic experiences.”
https://pubmed.ncbi.nlm.nih.gov/32872402/
https://www.mdpi.com/1422-0067/21/17/6252
“The endocannabinoid signaling system (ECSS) is altered by exposure to stress and mediates and modulates the effects of stress on the brain.
“Recent studies have shown that cannabidiol (CBD) could have a great therapeutic potential for treating disorders such as chronic pain and anxiety. In the target article, the authors propose that CBD modulates serotonergic transmission and reverses allodynia and anxiety-like behaviour in a rat model of neuropathic pain. Furthermore, this study shows an antinociceptive effect mediated by TRPV1 and partially by 5-HT1A receptors, as well as an anxiolytic effect mediated by 5-HT1A receptors.”
“Posttraumatic stress disorder (PTSD) may stem from the formation of aberrant and enduring aversive memories. Some PTSD patients have recreationally used Cannabis, probably aiming at relieving their symptomatology.
“Cannabidiol (
“The major phytocannabinoid cannabidiol (
“The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality.
“Chronic stress causes a variety of physiological and behavioral alterations, including social impairments, altered endocrine function, and an increased risk for psychiatric disorders. Thereby, social stress is one of the most effective stressful stimuli among mammals and considered to be one of the major risk factors for the onset and progression of neuropsychiatric diseases.
“Despite the increasing prevalence and acceptance of the medical 
“Considering data from in vitro and in vivo studies,