“The endogenous
cannabinoid (endocannabinoid) system regulates a diverse array of physiological processes and unsurprisingly possesses considerable potential targets for the potential treatment of numerous disease states, including two receptors (i.e., CB
1 and CB
2 receptors) and enzymes regulating their endogenous ligands
N-arachidonoylethanolamine (anandamide) and 2-arachidonyl glycerol (2-AG).
Increases in brain levels of endocannabinoids to pathogenic events suggest this system plays a role in compensatory repair mechanisms.
Traumatic brain injury (TBI) pathology remains mostly refractory to currently available drugs, perhaps due to its heterogeneous nature in etiology, clinical presentation, and severity. Here, we review pre-clinical studies assessing the therapeutic potential of
cannabinoids and manipulations of the endocannabinoid system to ameliorate TBI pathology.
Specifically, manipulations of endocannabinoid degradative enzymes (e.g., fatty acid amide hydrolase, monoacylglycerol lipase, and α/β-hydrolase domain-6), CB
1and CB
2 receptors, and their endogenous ligands have shown promise in modulating cellular and molecular hallmarks of TBI pathology such as; cell death, excitotoxicity, neuroinflammation, cerebrovascular breakdown, and cell structure and remodeling.
TBI-induced behavioral deficits, such as learning and memory, neurological motor impairments, post-traumatic convulsions or seizures, and anxiety also respond to manipulations of the endocannabinoid system.
As such, the endocannabinoid system possesses potential drugable receptor and enzyme targets for the treatment of diverse TBI pathology.
Yet, full characterization of TBI-induced changes in endocannabinoid ligands, enzymes, and receptor populations will be important to understand that role this system plays in TBI pathology.
Promising classes of compounds, such as the plant-derived phytocannabinoids, synthetic
cannabinoids, and endocannabinoids, as well as their non-
cannabinoid receptor targets, such as TRPV1 receptors, represent important areas of basic research and potential therapeutic interest to treat TBI.”
“Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage which is a critical event in the course of neurodegenerative diseases. It is still not fully elucidated, however, whether oxidative stress is the primary trigger or a consequence in process of neurodegeneration.
Recent Advances: Increasing evidence suggests that oxidative stress is involved in the propagation of neuronal injury and consequent inflammatory response, which in concert promote development of pathological alterations characteristic of most common neurodegenerative diseases.
Critical Issue: Accumulating recent evidence also suggests that there is an important interplay between the lipid endocannabinoid system (ECS; comprising of the main cannabinoid 1 and 2 receptors (CB1 and CB2), endocannabinoids and their synthetic and metabolizing enzymes) and various key inflammatory and redox-dependent processes.
“The endocannabinoid system (ECS), and agonists acting on 
“The 
“The noradrenergic system has been shown to play a key role in the regulation of stress responses, arousal, mood, and emotional states. Corticotropin-releasing factor (CRF) is a primary mediator of stress-induced activation of noradrenergic neurons in the nucleus locus coeruleus (LC).
The endocannabinoid (eCB) system also plays a key role in modulating stress responses, acting as an “anti-stress” neuro-mediator.
In the present study, we investigated the cellular sites for interactions between the