Category Archives: Endocannabinoid System

Seeing over the horizon – targeting the endocannabinoid system for the treatment of ocular disease.

Posted on by

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/26565550

Cannabinoid CB1 receptors and mTORC1 signalling pathway interact to modulate glucose homeostasis.

Posted on by

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/26563389

Endocannabinoid regulation of nausea is mediated by 2-arachidonoylglycerol (2-AG) in the rat visceral insular cortex.

Posted on by

“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.

Posted on by

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/26539529

http://www.hindawi.com/journals/bmri/2015/839403/

Activation of Endocannabinoid System Is Associated with Persistent Inflammation in Human Aortic Aneurysm.

Posted on by

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/26539497

Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression?

Posted on by

“The endocannabinoid (eCB) system, an endogenous lipid signaling system, appears to be dysregulated in depression. The role of endocannabinoids (eCBs) as potent immunomodulators, together with the accumulating support for a chronic low-grade inflammatory profile in depression, suggests a compelling hypothesis for a fundamental impairment in their intercommunication, in depression.

OBJECTIVE:

We aim to review previous literature on individual associations between the immune and eCB systems and depression. It will focus on peripheral and central mechanisms of crosstalk between the eCB and immune systems. A potential dysregulation in this crosstalk will be discussed in the context of depression.

RESULTS:

Investigations largely report a hypoactivity of the eCB system and increased inflammatory markers in individuals with depression. Findings depict a multifaceted communication whereby immunocompetent and eCB-related cells can both influence the suppression and enhancement of the other’s activity in both the periphery and central nervous system. A dysregulation of the eCB system, as seen in depression, appears to be associated with central and peripheral concentrations of inflammatory agents implicated in the pathophysiology of this illness.

CONCLUSION:

The eCB and immune systems have been individually associated with and implicated in pathogenic mechanisms of depression. Both systems tightly regulate the other’s activity. As such, a dysregulation in this crosstalk has potential to influence the onset and maintenance of this neuropsychiatric illness. However, few studies have investigated both systems and depression conjointly. This review highlights the demand to consider joint eCB-immune interactions in the pathoetiology of depression.”

http://www.ncbi.nlm.nih.gov/pubmed/26483037

Endocannabinoid signaling mediates oxytocin-driven social reward.

Posted on by

Image result for Proc Natl Acad Sci U S A.

“Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.”  http://www.ncbi.nlm.nih.gov/pubmed/26504214

“In conclusion, our results illuminate a mechanism underlying the prosocial actions of oxytocin, and provide unexpected insights on possible neural substrates involved in the social facilitation caused by marijuana. Pharmacological modulation of oxytocin-driven anandamide signaling (by using, for example, FAAH inhibitors) might open new avenues to treat social impairment in autism spectrum disorders.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653148/

Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes.

Posted on by

“Increased activity of the endocannabinoid system has emerged as a pathogenic factor in visceral obesity, which is a risk factor for type 2 diabetes mellitus (T2DM).

The endocannabinoid system is composed of at least two G-protein-coupled receptors (GPCRs), the cannabinoid receptor type 1 (CB1), and the cannabinoid receptor type 2 (CB2).

Downregulation of CB1 activity in rodents and humans has proven efficacious to reduce food intake, abdominal adiposity, fasting glucose levels, and cardiometabolic risk factors.

Unfortunately, downregulation of CB1 activity by universally active CB1 inverse agonists has been found to elicit psychiatric side effects, which led to the termination of using globally active CB1 inverse agonists to treat diet-induced obesity.

Interestingly, preclinical studies have shown that downregulation of CB1 activity by CB1 neutral antagonists or peripherally restricted CB1 inverse agonists provided similar anorectic effects and metabolic benefits without psychiatric side effects seen in globally active CB1 inverse agonists.

Furthermore, downregulation of CB1 activity may ease endoplasmic reticulum and mitochondrial stress which are contributors to obesity-induced insulin resistance and type 2 diabetes.

This suggests new approaches for cannabinoid-based therapy in the management of obesity and obesity-related metabolic disorders including type 2 diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/26498013

The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons.

Posted on by

“The molecular composition of the cannabinoid type 1 (CB1) receptor complex beyond the classical G-protein signaling components is not known.

Using proteomics on mouse cortex in vivo, we pulled down proteins interacting with CB1 in neurons and show that the CB1 receptor assembles with multiple members of the WAVE1 complex and the RhoGTPase Rac1 and modulates their activity…

This study reports novel signaling mechanisms for cannabinoidergic modulation of the nervous system and demonstrates a previously unreported role for the WAVE1 complex in therapeutic applications of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/26496209

Further Characterization of Hemopressin Peptide Fragments in the Opioid and Cannabinoid Systems.

Posted on by

“Hemopressin, so-called because of its hypotensive effect, belongs to the derivatives of the hemoglobin α-chain. It was isolated from rat brain membrane homogenate by the use of catalytically inactive forms of endopeptidase 24.15 and neurolysin. Hemopressin has antihyperalgesic features that cannot be prevented by the opioid receptor antagonist, naloxone.

Here, we further confirm that hemopressins can modulate CB1 receptors and can have a slight modulatory effect on the opioid system.”

http://www.ncbi.nlm.nih.gov/pubmed/26465932