“Evidence has accumulated over the last few years suggesting that endocannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. In fact, exogenous and endogenous cannabinoids were shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms,”
Category Archives: Endocannabinoid System
The endocannabinoid system as a target for the treatment of neuronal damage.
“Cannabinoids have been proposed as clinically promising neuroprotective molecules, based on their capability to normalize glutamate homeostasis, reducing excitotoxicity, to inhibit calcium influx, lowering intracellular levels and the subsequent activation of calcium-dependent destructive pathways, and to reduce the generation of reactive oxygen intermediates or to limit their toxicity, decreasing oxidative injury.
Cannabinoids are also able to decrease local inflammatory events by acting on glial processes that regulate neuronal survival, and to restore blood supply by reducing vasocontriction produced by several endothelium-derived factors.
Treatment of neurodegenerative disorders is a challenge for neuroscientists and neurologists. Unhappily, the efficacy of available medicines is still poor and there is an urgent need for novel neuroprotective agents. Cannabinoids can serve this purpose given their recognized antiexcitotoxic, antioxidant and anti-inflammatory properties.”
The endocannabinoid system in guarding against fear, anxiety and stress.
“The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment.
eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders.
An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.”
http://www.ncbi.nlm.nih.gov/pubmed/26585799
Cannabinoids in the management of chronic pain: a front line clinical perspective.
“Chronic pain is an escalating public health problem. Currently available treatments are inadequate to control chronic pain conditions, and there is a critical need for novel treatments.
Over a half century of elegant preclinical research has identified the presence of a sophisticated endocannabinoid system that is part of our natural pain and immune defense network.
Convergent work has supported the significant potential to exploit this system to decrease pain and inflammation.
Although the clinical research remains in its infancy, recent systematic reviews have found that 25 of 30 randomized controlled trials have demonstrated a significant analgesic effect.
The authors concluded that cannabinoids currently available for clinical use demonstrate a modest analgesic effect and are safe for the management of chronic pain.
There is a critical need for more translational research so that the excellent work of Dr. Itai Bab and our basic science colleagues around the world can move forward in providing novel cannabinoid-based medicines.
This should include more potent analgesics that are limited in side effects with several routes of delivery. Our patients deserve additional agents for pain control with a novel mechanism of action, and cannabinoids are the new frontier.”
The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction.
“Despite the fact that the cannabinoid receptor type 1 (CB1R) plays a pivotal role in emotional memory processing in different regions of the brain, its function in the retrosplenial cortex (RSC) remains unknown. Here, using contextual fear conditioning in rats, we showed that a post-training intra-RSC infusion of the CB1R antagonist AM251 impaired, and the agonist CP55940 improved, long-term memory consolidation. Additionally, a post-reactivation infusion of AM251 enhanced memory reconsolidation, while CP55940 had the opposite effect. Finally, AM251 blocked extinction, whereas CP55940 facilitated it and maintained memory extinguished over time. Altogether, our data strongly suggest that the cannabinoid system of the RSC modulates emotional memory.”
Seeing over the horizon – targeting the endocannabinoid system for the treatment of ocular disease.
“The observation that marijuana reduces intraocular pressure was made by Hepler and Frank in the 1970s. Since then, there has been a significant body of work investigating cannabinoids for their potential use as therapeutics.
To date, no endocannabinoid system (ECS)-modulating drug has been approved for clinical use in the eye; however, recent advances in our understanding of the ECS, as well as new pharmacological tools, has renewed interest in the development of ocular ECS-based therapeutics.
This review summarizes the current state-of-affairs for the use of ECS-modulating drugs for the treatment of glaucoma and ocular inflammatory and ischemic disease.”
Cannabinoid CB1 receptors and mTORC1 signalling pathway interact to modulate glucose homeostasis.
“The endocannabinoid system (ECS) is an inter-cellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and beta-cell mass expansion.
The mammalian target of rapamycin complex 1 (mTORC1) is a key intra-cellular pathway involved in energy homeostasis and known to importantly affect pancreatic islet’s physiology.
These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole organism level, which could have implications for the development of new therapeutic approaches for pancreatic beta-cell diseases.”
Endocannabinoid regulation of nausea is mediated by 2-arachidonoylglycerol (2-AG) in the rat visceral insular cortex.
“Cannabinoid (CB) agonists suppress nausea in humans and animal models; yet, their underlying neural substrates remain largely unknown.
Evidence suggests that the visceral insular cortex (VIC) plays a critical role in nausea. Given the expression of CB1 receptors and the presence of endocannabinoids in this brain region, we hypothesized that the VIC endocannabinoid system regulates nausea…
Taken together, these findings provide compelling evidence that acute nausea selectively increases 2-AG in the VIC, and suggests that 2-AG signaling within the VIC regulates nausea by reducing neuronal activity in this forebrain region.”
Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions.
“The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects.
The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions.
Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.”
Activation of Endocannabinoid System Is Associated with Persistent Inflammation in Human Aortic Aneurysm.
“Human aortic aneurysms have been associated with inflammation and vascular remodeling. Since the endocannabinoid system modulates inflammation and tissue remodeling, we investigated its components in human aortic aneurysms…
Our data provides evidence for endocannabinoid system activation in human aortic aneurysms, associated with persistent low-level inflammation and vascular remodeling.”