Tag Archives: endocannabinoid system

Getting High on the Endocannabinoid System

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“The endogenous cannabinoid system—named for the plant that led to its discovery—is one of the most important physiologic systems involved in establishing and maintaining human health.

Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. With its complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind.

By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.

…either stimulating or inhibiting the endocannabinoid system could have beneficial effects.

The most direct route of THC administration is by smoking marijuana or other forms of cannabis. Yet purified, FDA-approved medicinal preparations of THC are available in pill form… Why not just take a pill? There are several reasons that some patients prefer puffing over swallowing. One quantitatively minor factor is potential lethality.

It is possible to get a fatal overdose by swallowing too many THC pills at once, whereas documented evidence of death simply from smoking too much cannabis does not seem to exist.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/

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

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/

Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.

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“Experimental animal models of migraine have suggested the existence of interactions between the endocannabinoid system and pain mediation in migraine.

Extensive evidence has demonstrated a role for the cannabinoid-1 (CB1) receptor in antinociception.

…recent research suggests that also CB2 receptors, especially located outside the central nervous system, play a role in the perception of pain…

In this study we evaluated the role of CB2 receptors in two animal models of pain that may be relevant for migraine…

CONCLUSION:

These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”

http://www.ncbi.nlm.nih.gov/pubmed/24636539

Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.

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“The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer.

The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors… Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models…

Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.

The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.”

http://www.ncbi.nlm.nih.gov/pubmed/24634659

“Considering the numerous complex pathological mechanisms involved in the progression of AD, treatments targeting a single causal or modifying factor offer limited benefit. Cannabinoids, however, exhibit pleiotropic activity, targeting in parallel several processes that play key roles in AD…”

Full: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/

“Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation…Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.” http://www.jneurosci.org/content/25/8/1904.long

Therapeutic Potential of Cannabinoids in Schizophrenia.

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“Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia.

The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana’s psychoactive principle Δ9-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation.

…antipsychotic compounds which manipulate this system may provide a novel therapeutic target for the treatment of schizophrenia.

The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology.

Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/24605939