Category Archives: Endocannabinoid System

Cannabinoid receptor type 1 receptors on GABAergic vs. glutamatergic neurons differentially gate sex-dependent social interest in mice.

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“Abnormalities in social behavior are found in almost all psychiatric disorders, such as anxiety, depression, autism, and schizophrenia. Thus, comprehension of the neurobiological basis of social interaction is important for a better understanding of numerous pathologies and improved treatments.

Several findings have suggested that an alteration of cannabinoid receptor type 1 (CB1) receptor function could be involved in the pathophysiology of such disorders…

In conclusion, we provide evidence that CB1 receptors specifically modulate the social investigation of female mice in a neuronal subtype-specific manner.”

http://www.ncbi.nlm.nih.gov/pubmed/24698342

Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver.

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“Interleukin (IL)-17 is a proinflammatory and fibrogenic cytokine mainly produced by T-helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL-22.

Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti-inflammatory and antifibrogenic effects.

In the present study, we further investigated the mechanism underlying antifibrogenic properties of CB2 receptor and explored its effect on the profibrogenic properties of IL-17.

These data demonstrate that CB2 receptor activation decreases liver fibrosis by selectively reducing IL-17 production by Th17 lymphocytes via a STAT5-dependent pathway, and by blunting the proinflammatory effects of IL-17 on its target cells, while preserving IL-22 production.”

http://www.ncbi.nlm.nih.gov/pubmed/23813495

Anandamide Attenuates Th-17 Cell-Mediated Delayed-Type Hypersensitivity Response by Triggering IL-10 Production and Consequent microRNA Induction

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“Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions..

Cannabinoids are compounds derived from the Cannabis sativa plant and exert many effects on the immune system. Cannabinoids have potential as therapeutic agents in several different disease conditions, including experimental autoimmune hepatitis, Multiple Sclerosis, and Graft vs. Host Disease…

This report suggested a role of the endogenous cannabinoid system in regulation of allergic inflammation.

These studies also suggest that endogenous cannabinoid system is one of the homeostatic mechanisms that the body employs to down-regulate immune response to foreign antigens as well as combat autoimmunity.

Targeting of this system could yield valuable therapeutics in the future.”

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0093954

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

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“For centuries Cannabis sativa and cannabis extracts have been used in natural medicine.

Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis.

In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma.

Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications.

The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/19832688

Targeting the endocannabinoid system in the treatment of fragile X syndrome.

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“Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism, is caused by the silencing of the FMR1 gene, leading to the loss of fragile X mental retardation protein (FMRP), a synaptically expressed RNA-binding protein regulating translation.

The endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive performance, anxiety, nociception and seizure susceptibility, all of which are affected in FXS. The cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) are activated by phospholipid-derived endocannabinoids, and CB1R-driven long-term regulation of synaptic strength, as a consequence of mGluR5 activation, is altered in several brain areas of Fmr1 knockout mice.

We found that CB1R blockade in male Fmr1 knockout (Fmr1(-/y)) mice through pharmacological and genetic approaches normalized cognitive impairment, nociceptive desensitization, susceptibility to audiogenic seizures, overactivated mTOR signaling and altered spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic-like behavior. Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5.

Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS.”

http://www.ncbi.nlm.nih.gov/pubmed/23542787

Role of the cannabinoid system in the transit of beta-amyloid across the blood-brain barrier.

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“Emerging evidence suggests beta-amyloid (Aβ) deposition in the Alzheimer’s disease (AD) brain is the result of impaired clearance, due in part to diminished Aβ transport across the blood-brain barrier (BBB). Recently, modulation of the cannabinoid system was shown to reduce Aβ brain levels and improve cognitive behavior in AD animal models.

The purpose of the current studies was to investigate the role of the cannabinoid system in the clearance of Aβ across the BBB..

The current studies demonstrate, for the first time, a role for the cannabinoid system in the transit of Aβ across the BBB. These findings provide insight into the mechanism by which cannabinoid treatment reduces Aβ burden in the AD brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

http://www.ncbi.nlm.nih.gov/pubmed/23831388

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Effect of an acute consumption of a moderate amount of ethanol on plasma endocannabinoid levels in humans.

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“Animal experiments have shown that the endocannabinoid system (ECS) plays an important role in the regulation of ethanol intake. We investigated these effects in healthy volunteers who consumed a moderate amount of ethanol (red wine) and measured plasma levels of the endocannabinoids (ECs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) to test whether alcohol consumption influences the ECS in humans…

AEA, 2-AG and plasma glucose levels were significantly reduced after red wine consumption.

Water intake had no significant effect on AEA  but resulted in a gradual reduction in 2-AG concentrations…

The consumption of a moderate amount of red wine reduces plasma AEA and 2-AG concentrations, whereas the volume and caloric equivalent of the sugar containing, non-alcoholic liquid grape juice does not affect plasma ECs. Plain water has a differential effect on the ECS by reducing 2-AG concentrations without affecting AEA.”

http://www.ncbi.nlm.nih.gov/pubmed/22278319

Exercise, Manual Therapy, and the Endocannabinoid System: Why we’re all inherently potheads

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“Have you ever heard of the digestive system? The lymphatic system? How about the muscular and nervous systems? Of course you have. Science has been studying them for years, making breakthroughs in our understanding of their inner workings that have lead to advancements benefited humanity in ways we now take for granted.

How about the endocannabinoid system? Have you heard of that?  If your profession has nothing to do with the biological sciences, I would expect the answer to be no (save a few individuals).  Don’t feel bad however, I have asked this question to many health and medical professionals that I have taught over the years and have received many a blank stare or look of confusion.

What if I were to tell you that this biological system permeates the entire human body with receptors located in skeletal muscle, the digestive tract, adipose (fat) tissue, and throughout the peripheral and central nervous systems (including the brain)? Again, you would question why this system is not studied, discussed, or even mentioned in most in physiology/health classes.

What if I were to tell you that the Endocannabinoid system (or ECS):

–   Helps regulate the central control of energy balance

–   Helps regulate metabolic processes (including storage)

–   Plays a key role in the maintenance of bone mass

–   Regulates intestinal motility

–   Promotes/regulates sleep

–   Is involved in neuromodulation and immunomodulation in the immune system

–   Is involved in modulating insulin sensitivity

–   Is involved in the regulation of pain signaling

–   And much more”

http://functionalanatomyblog.com/2014/03/27/exercise-manual-therapy-and-the-endocannabinoid-system-why-were-all-inherently-potheads/

“Exercise activates the endocannabinoid system.”  http://www.ncbi.nlm.nih.gov/pubmed/14625449

“Exercise-induced endocannabinoid signaling is modulated by intensity.”  http://www.ncbi.nlm.nih.gov/pubmed/22990628

“Effects of exercise stress on the endocannabinoid system in humans under field conditions.”   http://www.ncbi.nlm.nih.gov/pubmed/22101870

Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth.

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“Because THC-like compounds are used to inhibit nausea and induce appetite in cancer patients, and anandamide appears to be an endogenous orexigenic mediator, the finding of possible antitumor effect for these substances might have a tremendous potential for therapeutic intervention in preventing the progression of cancer and, at the same time, in alleviating its symptoms.

Because multiple pathways are important for the proliferation of tumor cells and because combination therapies are often more effective than single-drug administration, cannabimimetic substances may complement other anticancer agents…”

http://www.fasebj.org/content/early/2001/12/02/fj.01-0320fje.long

“[Targeting the RAS signalling pathway in cancer].”  http://www.ncbi.nlm.nih.gov/pubmed/21715253

“Targeting the RAS oncogene.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804031/

Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.

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“The cannabinoid receptor type 2 (CB2) is a class A GPCR that was cloned in 1993 while looking for an alternative receptor that could explain the pharmacological properties of Δ(9)-tetrahydrocannabinol.

CB2 was identified among cDNAs based on its similarity in amino acid sequence to the CB1receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.

In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, peripheral nervous system, and gastrointestinal tract.

Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain, and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.

Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this Perspective, we seek to provide a concise update of progress in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/23865723