Category Archives: Endocannabinoid System

Marijuana For Migraines

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“Our brain’s own endogenous marijuana-like chemicals produce analgesia by modulating the entry of pain signals into the brain at the level of our spinal cord.

Future generations of pain relievers will likely be developed based upon the action of marijuana in the body.

The advantage of targeting the endogenous marijuana system is that only noxious or painful signals are blocked; normal touch sensation is normal.

This study may lead to the development of more effective migraine prevention and treatment.

The challenge will be to find a dose of marijuana that produces pain relief without disturbing normal cognitive function.”

 https://www.psychologytoday.com/blog/your-brain-food/201309/marijuana-migraines

http://www.thctotalhealthcare.com/category/headachemigraine/

Interactions between the endocannabinoid and nicotinic cholinergic systems: preclinical evidence and therapeutic perspectives.

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“Many behavioral and neurochemical effects of nicotine that are related to its addictive potential are reduced by pharmacological blockade or genetic deletion of type-1 cannabinoid receptors, inhibition of endocannabinoid uptake or metabolic degradation, and activation of peroxisome proliferator-activated-receptor-α. On the other hand, cholinergic antagonists at α7 nicotinic acetylcholine receptors as well as endogenous negative allosteric modulators of these receptors are effective in blocking dependence-related effects of cannabinoids.

CONCLUSIONS:

Pharmacological manipulation of the endocannabinoid system and endocannabinoid-like neuromodulators shows promise in the treatment of nicotine dependence and in relapse prevention. Likewise, drugs acting at nicotinic acetylcholine receptors might prove useful in the therapy of cannabinoid dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/26728894

Cannabinoid receptor-specific mechanisms to ameliorate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation.

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“Sickle cell anaemia is a manifestation of a single point mutation in haemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life.

Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice.

Morphine is the common analgesic treatment but also remains a major challenge due to the side effects and ability to activate mast cells. Therefore, we examined the cannabinoid receptor-specific mechanisms to ameliorate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor 2 deleted sickle mice.

We show that cannabinoids ameliorate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2.

Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice.

This study provides a “proof of principle” for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anaemia.”

Oxyradical Stress, Endocannabinoids, and Atherosclerosis.

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“Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation.

Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression.

Overactive NADPH oxidase (Nox) produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS) have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress.

In addition to inflammation and ROS, the endocannabinoid system (eCB) is also important in atherogenesis.

Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis.

For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects.

The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ) is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG).

Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress.

This review will highlight the role of reactive oxygen species (ROS) in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis.

In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis.

We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology.”

http://www.ncbi.nlm.nih.gov/pubmed/26702404

http://www.thctotalhealthcare.com/category/atherosclerosis-2/

An Introduction to the Endogenous Cannabinoid System.

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“The endocannabinoid system (ECS) is a widespread neuromodulatory system that plays important roles in central nervous system development, synaptic plasticity, and the response to endogenous and environmental insults.

The ECS comprises cannabinoid receptors, endogenouscannabinoids (endocannabinoids), and the enzymes responsible for the synthesis and degradation of the endocannabinoids.

The most abundant cannabinoid receptors are the CB1 cannabinoid receptors; however, CB2 cannabinoid receptors, transient receptor potential channels, and peroxisome proliferator activated receptors are also engaged by some cannabinoids.

Exogenous cannabinoids, such as tetrahydrocannabinol, produce their biological effects through their interactions with cannabinoid receptors.

The best-studied endogenous cannabinoids are 2-arachidonoyl glycerol and arachidonoyl ethanolamide (anandamide). Despite similarities in chemical structure, 2-arachidonoyl glycerol and anandamide are synthesized and degraded by distinct enzymatic pathways, which impart fundamentally different physiologic and pathophysiologic roles to these two endocannabinoids.

As a result of the pervasive social use of cannabis and the involvement of endocannabinoids in a multitude of biological processes, much has been learned about the physiologic and pathophysiologic roles of the ECS.

This review provides an introduction to the ECS with an emphasis on its role in synaptic plasticity and how the ECS is perturbed in schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/26698193

The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation.

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“UV, including UVA and UVB radiation, is one of the most ubiquitous environmental stress factors to human skin and leads to redox imbalance and, consequently, photoaging and cancer development. The aim of the study was to verify which skin cells, keratinocytes or fibroblasts, were more susceptible to UVA or UVB irradiation.

The results presented in this paper demonstrate a strong relationship between UV-induced oxidative stress and changes in the endocannabinoid system.

The differences demonstrated in the response of the tested cells to UV irradiation allow for a better understanding of the mechanisms occurring in the human skin, which may be exploited for future therapies in dermatology.”

http://www.ncbi.nlm.nih.gov/pubmed/26674123

Cannabis for posttraumatic stress disorder: A neurobiological approach to treatment.

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“The endocannabinoid system is intricately involved in regulation of the neurobiological processes, which underlie the symptomatology of posttraumatic stress disorder (PTSD). This article discusses the neurobiological underpinnings of PTSD and the use of cannabis for treating PTSD in the New Mexico Medical Cannabis Program.”

GPR55 – a putative “type 3” cannabinoid receptor in inflammation.

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“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor.

Therefore, GPR55 has emerged as a putative “type 3″ cannabinoid receptor, establishing a novel class of cannabinoid receptor.

Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”

 http://www.ncbi.nlm.nih.gov/pubmed/26669245

Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development.

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“The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2) which have been explored as potential therapeutic targets for drug discovery and development.

Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2receptors.

In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems.

Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative.

The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.”

The therapeutic aspects of the endocannabinoid system (ECS) for cancer and their development: from nature to laboratory.

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“The endocannabinoid system (ECS) is a group of neuromodulatory lipids and their receptors, which are widely distributed in mammalian tissues. ECS regulates various cardiovascular, nervous, and immune system functions inside cells.

In recent years, there has been a growing body of evidence for the use of synthetic and natural cannabinoids as potential anticancer agents.

For instance, the CB1 and CB2 receptors are assumed to play an important role inside the endocannabinoid system. These receptors are abundantly expressed in the brain and fatty tissue of the human body.

Despite recent developments in molecular biology, there is still a lack of knowledge about the distribution of CB1 and CB2 receptors in the human kidney and their role in kidney cancer. To address this gap, we explore and demonstrate the role of the endocannabinoid system in renal cell carcinoma (RCC).

In this brief overview, we elucidate the therapeutic aspects of the endocannabinoid system for various cancers and explain how this system can be used for treating kidney cancer.

Overall, this review provides new insights into cannabinoids’ mechanisms of action in both in vivo and in vitro models, and focuses on recent discoveries in the field.”