The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases

Abstract

The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation.

The application of cannabidiol in the treatment of glioblastoma

“…The well-characterized endocannabinoids, i.e. ligands biosynthesized in cells, are two derivatives of unsaturated fatty acids -anandamide or N-arachidonoyl ethanolamine (AEA) and 2-arachidonylglycerol (2-AG) (10). Both compounds are synthesized from arachidonic acid-containing phospholipids (16).…”

“…researchers' attention has been focused on understanding the importance of the ECS in human health. The ECS is comprised of endocannabinoids, cannabinoid receptors, and the proteins that are involved in the transport, degradation, and synthesis of cannabinoids, such as diacylglycerol (DAG) lipase isozymes α and β, fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and N-acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) (10). The concept of 'endocannabinodiome' introduced by Cristino et al comprises all system components and signaling pathways that are modulated by the cannabinoids' activity (11).…”

Special Issue: Therapeutic Potential for Cannabis and Cannabinoids

“…Chacon et al review some of the less abundant (“secondary”) terpenes found in Cannabis and the potential therapeutic utility of some of these molecules to treat a number of medical conditions [ 19 ]. Tudorancea and colleagues review the evidence that supports targeting the endocannabinoid system to treat age-related conditions such as Alzheimer’s disease, osteoarthritis, and hypertension [ 20 ]. Finally, Sionov and Steinberg examine the antimicrobial activity of endocannabinoids and phytocannabinoids.…”

Systematic Modification of the Substitution Pattern of the 7-Hydroxy-5-oxopyrazolo[4,3-b]pyridine-6-carboxamide Scaffold Enabled the Discovery of New Ligands with High Affinity and Selectivity for the Cannabinoid Type 2 Receptor

“…The pathophysiological relevance of the endocannabinoid system has been demonstrated in a variety of diseases including pain, neurodegenerative diseases, seizures, psychiatric disorders, obesity, metabolic diseases, and cancer [ 2 ]. Thus, direct targeting of the receptors as well as indirect targeting via modulation of the endogenous machinery involved in this system can provide a successful therapeutic outcome [ 3 ]. Nevertheless, manipulating such a high-complex system can be particularly challenging when we consider possible multidirectional effects that could be triggered by affecting other mediators that are biochemically related to endocannabinoids [ 1 ].…”

“…CB1 and CB2 receptors share 44% amino acid homology and differ in their localization in the human body [ 3 ]. The CB1 receptor is one of the most abundant GPCRs in the brain, and this distribution correlates with its role in controlling motor function, cognition and memory, and pain relief [ 4 ].…”