The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Abstract

The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

“…This system involves endogenous lipid mediators called endocannabinoids, of which the most well-known are 2-arachidonoylglycerol and anandamide, which are synthesized from the pool of arachidonic acid in cell membrane phospholipids. The modulation of this system with cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that are currently under development offers some potential for treating a number of diseases [200]. The endocannabinoid system (ECS), via the activation of the type-1 cannabinoid receptor (CB1), is involved in the process of exostasis, i.e., overeating and storage due to the anticipation of future energy needs, and thus adds some adaptatory regulations to homeostasis [201].…”

Components of the Endogenous Cannabinoid System as Potential Biomarkers for Interstitial Cystitis/Bladder Pain Syndrome

“…We found five studies reporting the levels of endocannabinoid ligands and fatty acid ethanolamides in experimental models of interstitial cystitis ( Table 2 ). Fatty acid ethanolamides are endocannabinoid-like compounds that interact with receptors outside of CB1R and CB2R [ 66 ]. Palmitoylethanolamide (PEA) was significantly increased in the bladder tissue of all the relevant studies except the study by Charrua et al, where PEA was downregulated in an LPS-induced cystitis model using Wistar rats [ 67 ].…”

Targeting the Endocannabinoid System: From the Need for New Therapies to the Development of a Promising Strategy. What About Pancreatic Cancer?

“…Natural and synthetic analog of the marijuana plant Cannabis sativa L. affect several human diseases such as neurological, cardiovascular, and autoimmune disorders, pain, inflammation, and diabetes as well as cancer. As a result, the medicinal use of cannabis has potential against a variety of diseases; the US Food and Drug Administration has already approved the application of certain relative drug regimens (89).…”