Endo-cannabinoid System’s Mechanisms and Functions

Cannabinoids from plants activate one of the most healing and ancestral endocannabinoid systems that have been gifted to all veterbra animals including humans. In this analysis, I will examine what the endocannabinoid system (ECS) is, its components and mechanisms. (Section A) In the second section, I will study a few of the ECS’s functions. (Section B)

Section A

The Endocannabinoid System

The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the mammalian central nervous system (including, but not limited to the brain) and peripheral nervous system. The endocannabinoid system is involved in regulating homeostasis in general and in particular, a wide variety of physiological, cognitive and survival processes including but not limited to fertility, (1) pregnancy, (3) pre and postnatal development of the infant, (3) appetite, pain-sensation, mood, memory, and, among other processes, in mediating the pharmacological effects of cannabis the plant itself. (4, 5).

The ECS is also involved in mediating some of the physiological and cognitive effects of voluntary physical exercise in humans and other animals, such as contributing to exercise-induced euphoria as well as modulating locomotor activity and motivational salience for rewards. (6-9) A fact that reminds us that we are creatures of movement. In effect, the plasma concentration of certain endocannabinoids (i.e., anandamide) have been found to rise during physical activity (6,7).

Endocannabinoid Receptors

Two primary endocannabinoid receptors have been identified: CB1, first cloned in 1990; and CB2, cloned in 1993. CB1 receptors are found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the endocannabinoid ligand (binding molecule), anandamide, as well as its mimetic phytocannabinoid, THC.

One other main endocannabinoid is 2-arachidonoylglycerol (2-AG) which is active at both cannabinoid receptors, along with its own mimetic phytocannabinoid, CBD. 2-AG and CBD are involved in the regulation of appetite, immune system functions and pain management. (10-12).

Homeostasis and Joie de Vivre. Proper regulation is crucial for ensuring survival

As we saw, homeostasis is one of the key processes of heath, longevity and the ECS. To understand homeostasis, we can think of Goldilocks and the three bears or observe a fulcrum’s swings. The Goldilocks classic fairy tale illustrated the Greek-old idea that the best outcome often lies somewhere in the middle, between two extremes. We don’t want things too hot or too cold, but just right, in a dynamic balance that favors Life.

As Jean Bernard and others taught, homeostasis is the concept that most biological systems are actively regulated to maintain conditions within a narrow range. Our body doesn’t want its temperature to be too hot or too cold, blood sugar levels too high or too low, blood PH too variable, blood pressure to high or too low. Conditions need to be just right for our cells to maintain optimum performance.

One of Evolution’s and Life’s challenges is Resilience, or how to get back to homeostasis once a deviation from the balance has occurred. Because of its crucial role in homeostasis, the ECS is widespread throughout the animal kingdom. Its key pieces evolved a long time ago, and the ECS can be found in all vertebrate species.

Over the years, multiple mechanisms have evolved to draw imbalances back to the Goldilocks or homeostatic zone. In this perspective, the body’s endocannabinoid system (ECS) is a vital molecular “ balancing” system for helping maintain homeostasis.

Contrarily to many other signaling systems, the ECS is often engaged only when and where it’s needed in a pro-homeostatic  way, meaning  that this system of chemical signals gets temporarily activated following deviations from cellular homeostasis. When such deviations are non-physiological, the temporarily activated ECS attempts, in a space- and time-selective manner, to restore the previous physiological situation called homeostasis.

Three Key Players of the Endocannabinoid System (ECS)

The three key components of the ECS are: Cannabinoid receptors found on the surface of cells.  Endocannabinoids, small molecules that activate cannabinoid receptors. Metabolic enzymes that break down endocannabinoids after they are used

Cannabinoid Receptors

Cannabinoid receptors sit on the surface of cells and “listen” to conditions outside the cell. They transmit information about changing conditions to the inside of the cell, kick-starting the appropriate cellular response.

There are two major cannabinoid receptors: CB1 and CB2. These aren’t the only cannabinoid receptors, but they were the first ones discovered and remain the best-studied. CB1 receptors are one of the most abundant receptor types in the brain. These are the receptors that interact with THC to get people high. CB2 receptors are more abundant outside of the nervous system, in places like the immune system. However, both receptors can be found throughout the body.

Endocannabinoids

Endocannabinoids are molecules that, like the plant cannabinoid THC, bind to and activate cannabinoid receptors. However, unlike THC, endocannabinoids are produced naturally by cells in the human body (“endo” means “within,” as in within the body).

There are two major endocannabinoids: anandamide and 2-AG. These endocannabinoids are made from fat-like molecules within cell membranes, and are synthesized on-demand. This means that they get made and used exactly when they’re needed, rather than packaged and stored for later use like many other biological molecules. Anandamide is an endogenous cannabinoid neurotransmitter that binds to cannabinoid receptors

Cannabinoids are a class of molecules characterized by their ability to activate cannabinoid receptors like CB1 and CB2. Anandamide and 2-AG are the two major endocannabinoids produced naturally in the body. THC is the psychoactive plant cannabinoid produced by Cannabis. All three of these cannabinoids can activate the CB1 and CB2 receptors, although each one has a different potency at each receptor.

Metabolic Enzymes

The third piece of the endocannabinoid triad includes the metabolic enzymes that quickly destroy endocannabinoids once they are used. The two big enzymes are FAAH, which breaks down anandamide, and MAGL, which breaks down 2-AG. These enzymes ensure that endocannabinoids get used when they’re needed, but not for longer than necessary. This distinguishes endocannabinoids from many other molecular signals in the body, such as hormones or classical neurotransmitters, which can persist for many seconds or minutes, or get packaged and stored for later use.

Enzymes are molecules that accelerate chemical reactions in the body, often for breaking down molecules. FAAH and MAGL are key players in the ECS because they quickly break down endocannabinoids. FAAH breaks down anandamide, while MAGL breaks down 2-AG. These enzymes break down endocannabinoids very quickly, but are not effective at breaking down plant cannabinoids like THC.

The three key components of the ECS can be found within almost every major system of the body. When something brings a cell out of its Goldilocks zone, these three pillars of the ECS are often called upon to bring things back, thus maintaining homeostasis.

Section B

Illustrations

Endocannabinoid Homeostatic Regulation of Brain Cell Firing

Brain cells (neurons) communicate by sending electrochemical signals to each another. Given the “entourage effect”, each neuron must listen to its partners neurons to decide whether it will fire off its own signal at any given moment. However, as with other cells, neurons can get overwhelmed with too much signaling. Just like in romance and with marketers, if neurons get overloaded by signals, it can be toxic and counter-productive. That’s where endocannabinoids come in, to put some semblance of meaningful balance in the biochemical processes of Life.

When neurons become overactive and send too many signals to the neuron or neurons that are “listening”, the neuron that’s listening will make endocannabinoids specifically where it’s connected to the overactive neuron. Those endocannabinoids will travel back to the “loud” neuron where they bind to CB1 receptors, transmitting a signal that instructs it to quiet down, to keep cool thereby maintaining homeostasis.

As the example above illustrates, endocannabinoids travel backwards in order to correct the imbalance, what they put out is  known as retrograde signals, it’s a feedback loop mechanism that is essential to maintain this thing we call Life.

Most of the time, the information flow between neurons is strictly in one direction, from “sender” neurons that release neurotransmitter signals to “receiver” neurons that listen to those signals. Endocannabinoids allow receiver neurons to regulate how much input they’re getting, and they do this by sending retrograde signals (endocannabinoids) back to overactive sender neurons.

Endocannabinoid Regulation of Inflammation

Inflammation is a natural protective reaction the immune system has in response to infection, malignancy or other forms of physical damage. The purpose of inflammation is to remove pathogens (germs) or damaged tissue. The inflamed area is produced by fluid and immune cells moving into the area to do the clean up work in order to restore some semblance of balance.

It’s important that inflammation be limited to the location of damage and doesn’t persist longer than needed, which can cause harm. Chronic inflammation and auto-immune diseases are examples of the immune system getting over-activated. When that happens, the inflammatory response lasts too long (which results in chronic inflammation and tissue damage) or gets directed toward healthy cells via the molecular mimicry mechanism (which is known as auto-immunity).

Evidence suggests that endocannabinoids may function as both neuromodulators and immunomodulators in the immune system. They seem to serve an autoprotective role to ameliorate muscle spasms, inflammation, and other symptoms of multiple sclerosis and skeletal muscle spasms. (13)

Functionally, the activation of cannabinoid receptors has been demonstrated to play a role in the activation of GTPases in macrophages, neutrophils, and BM cells. These receptors have also been implicated in the proper migration of B cells into the marginal zone (MZ) and the regulation of healthy IgM levels. (14)

Some disorders seem to trigger an upregulation of cannabinoid receptors selectively in cells or tissues related to symptom relief and inhibition of disease progression, such as in that rodent neuropathic pain model, where receptors are increased in the spinal cord microglia, dorsal root ganglion, and thalamic neurons. (15)

ECS, Multiple Sclerosis and other auto-immune diseases

Consider a normal immune response triggered by a bacterial infection. First, immune cells detect the presence of bacteria and release pro-inflammatory molecules that tell other immune cells to come and join the fight. Endocannabinoids get released as well, which also signal to other immune cells for assistance and likely help limit the inflammatory response so it isn’t excessive. By tightly regulating inflammation, the immune system can destroy germs or remove damaged tissue, and then stop. This prevents excessive inflammation, allowing cells, and thus the body, to return to homeostasis. In this perspective, Professor Prakash Nagarkatti, Vice President for Research at the University of South Carolina whose laboratory studies endocannabinoid regulation of immune responses observed the following.

“Most of our research demonstrates that endocannabinoids are produced upon activation of immune cells and may help regulate the immune response by acting as anti-inflammatory agents. Thus, interventions that manipulate the metabolism or production of endocannabinoids may serve as a novel treatment modality against a wide range of inflammatory disease.” (Source)

With regard the multiple sclerosis, historical records from ancient China and Greece suggest that preparations of Cannabis indica were commonly prescribed to ameliorate multiple sclerosis-like symptoms such as tremors and muscle pain. Modern research has confirmed these effects wherein both endogenous and exogenous agonists showed ameliorating effects on tremor and spasticity. Pharmaceutical THC preparations such as dronabinol however don’t have the same beneficial effects in humans as the natural herb. (16-17)

Due to increasing use of medical Cannabis and rising incidence of multiple sclerosis patients who self-medicate with the cannabis, there has been much interest in exploiting the endocannabinoid system in the cerebellum to provide an effective relief. (18) In mouse models of multiple sclerosis, there is a profound reduction and reorganization of CB1 receptors in the cerebellum. (19). Serial sections of cerebellar tissue subjected to immunohistochemistry revealed that this aberrant expression occurred during the relapse phase but returned to normal during the remitting phase of the disease. (ibid).

Other studies suggest that CB1 agonists promote the survival of oligodendrocytes in vitro in the absence of growth and trophic factors; in addition, these agonist have been shown to promote mRNA expression of myelin lipid protein. (Kittler et al., 2000; Mollna-Holgado et al., 2002).

Taken together, these studies point to the real possibility that cannabinoid treatment may not only be able to attenuate the symptoms of multiple sclerosis and other auto-immune diseases,  but also improve oligodendrocyte function (reviewed in Pertwee, 2001; Mollna-Holgado et al., 2002). 2-AG stimulates proliferation of a microglial cell line by a CB2 receptor dependent mechanism, and the number of microglial cells is increased in multiple sclerosis. (20).

Female reproduction

The developing embryo expresses cannabinoid receptors early in development that are responsive to anandamide secreted in the uterus. This signaling is important in regulating the timing of embryonic implantation and uterine receptivity. In mice, it has been shown that anandamide modulates the probability of implantation to the uterine wall. For example, in humans, the likelihood of miscarriage increases if uterine anandamide levels are too high or low. (21)

These results suggest that intake of exogenous cannabinoids (e.g. cannabis) can decrease the likelihood for pregnancy for women with high anandamide levels, and alternatively, it can increase the likelihood for pregnancy in women whose anandamide levels were too low. (22, 23).

Sleep

Concerning sleep bedtime, increased endocannabinoid signaling within the central nervous system will usually promotes sleep-inducing effects. Supporting this piece of allegation, a lab test that administered  anandamide in rats has been shown to decrease wakefulness and increase slow-wave sleep and REM sleep. (24)

Administration of anandamide into the basal forebrain of rats has also been shown to increase levels of adenosine, which plays a role in promoting sleep and suppressing arousal. (25) REM sleep deprivation in rats has been demonstrated to increase CB1 receptor expression in the central nervous system.. (26)

Furthermore, anandamide levels possess a circadian rhythm in the rat, with levels being higher in the light phase of the day, which is when rats are usually asleep or less active, since they are nocturnal.(27)

Physical exercise

It has been shown that aerobic exercise causes an increase in plasma anandamide levels, where the magnitude of this increase is highest at moderate exercise intensity (i.e., exercising at 70–80% maximum heart rate).

Increases in plasma anandamide levels are associated with psychoactive effects because anandamide is able to cross the blood–brain barrier and act within the central nervous system. Thus, because anandamide is a euphoriant and aerobic exercise is associated with euphoric effects, it has been proposed that anandamide partly mediates the short-term mood-lifting effects of exercise (e.g., the euphoria of a runner’s high) via exercise-induced increases in its synthesis.

In mice it was demonstrated that certain features of a runner’s high depend on cannabinoid receptors. Pharmacological or genetic disruption of cannabinoid signaling via cannabinoid receptors prevents the analgesic and anxiety-reducing effects of running. (28)

Stress response

While the secretion of glucocorticoids in response to stressful stimuli is an adaptive response necessary for an organism to respond appropriately to a stressor, persistent secretion may be harmful. The endocannabinoid system has been implicated in the habituation of the hypothalamic-pituitary-adrenal axis (HPA axis) to repeated exposure to restraint stress. Studies have demonstrated differential synthesis of anandamide and 2-AG during tonic stress. A decrease of anandamide was found along the axis that contributed to basal hypersecretion of corticosterone; in contrast, an increase of 2-AG was found in the amygdala after repeated stress, which was negatively correlated to magnitude of the corticosterone response. All effects were abolished by the CB1 antagonist AM251, supporting the conclusion that these effects were cannabinoid-receptor dependent. (29) These findings show that anandamide and 2-AG divergently regulate the HPA axis response to stress: while habituation of the stress-induced HPA axis via 2-AG prevents excessive secretion of glucocorticoids to non-threatening stimuli, the increase of basal corticosterone secretion resulting from decreased anandamide allows for a facilitated response of the HPA axis to novel stimuli.

Social behavior and Anxiety

These contrasting effects reveal the importance of the endocannabinoid system in regulating anxiety-dependent behavior. Results suggest that glutamatergic cannabinoid receptors are not only responsible for mediating aggression, but produce an anxiolytic-like function by inhibiting excessive arousal: excessive excitation produces anxiety that limited the mice from exploring both animate and inanimate objects. In contrast, GABAergic neurons appear to control an anxiogenic-like function by limiting inhibitory transmitter release. Taken together, these two sets of neurons appear to help regulate the organism’s overall sense of arousal during novel situations. (30)

Appetite

Evidence for the role of the endocannabinoid system in food-seeking behavior is supported by an abundance of evidentiary sources.  Indeed, the confirming data suggests that THC acts via CB1 receptors in the hypothalamic nuclei to directly increase appetite. (31) Furthermore, it is thought that hypothalamic neurons tonically produce endocannabinoids that work to tightly regulate hunger. The amount of endocannabinoids produced is inversely correlated with the amount of leptin in the blood. (32) For example, mice without leptin not only become massively obese but express abnormally high levels of hypothalamic endocannabinoids as a compensatory mechanism. Similarly, when these mice were treated with an endocannabinoid inverse agonists, such as rimonabant, food intake was reduced. When the CB1 receptor is knocked out in mice, these animals tend to be leaner and less hungry than wild-type mice. A related study examined the effect of THC on the hedonic (pleasure) value of food and found enhanced dopamine release in the nucleus accumbens and increased pleasure-related behavior after administration of a sucrose solution. (33). A related study found that endocannabinoids affect taste perception in taste cells. (34)  In taste cells, endocannabinoids were shown to selectively enhance the strength of neural signaling for sweet tastes, whereas leptin decreased the strength of this same response. While there is need for more research, these results suggest that cannabinoid activity in the hypothalamus and nucleus accumbens is related to appetitive, food-seeking behavior.

Energy balance and metabolism

The endocannabinoid system has been shown to have a homeostatic role by controlling several metabolic functions, such as energy storage and nutrient transport. It acts on peripheral tissues such as adipocytes, hepatocytes, the gastrointestinal tract, the skeletal muscles and the endocrine pancreas. It has also been implied in modulating insulin sensitivity. Through all of this, the endocannabinoid system may play a role in clinical conditions, such as obesity, diabetes, and atherosclerosis, which may also give it a cardiovascular role. (35)

Analgesia

The endocannabinoid most researched in pain is palmitoylethanolamide. Palmitoylethanolamide is a fatty amine related to anandamide, but saturated and although initially it was thought that palmitoylethanolamide would bind to the CB1 and the CB2 receptor, later it was found that the most important receptors are the PPAR-alpha receptor, the TRPV receptor and the GPR55 receptor. Palmitoylethanolamide has been evaluated for its analgesic actions in a great variety of pain indications. (36) and found to be safe and effective. Basically these data are proof of concept for endocannabinoids and related fatty amines to be therapeutically useful analgesics; palmitoylethanolamide is available under the brand names Normast and PeaPure as nutraceuticals. Endocannabinoids are also involved in placebo induced analgesia responses. (37)

Thermoregulation

Anandamide and N-arachidonoyl dopamine (NADA) have been shown to act on temperature-sensing TRPV1 channels, which are involved in thermoregulation.TRPV1 is activated by the exogenous ligand capsaicin, the active component of chili peppers, which is structurally similar to endocannabinoids. (38)

Drug-Resistant Seizures Control

The randomized, double-blind, placebo-controlled study published in The New England Journal of Medicine in May 2017 again confirmed what has long been known: that CBD offers relief for children with drug-resistant seizures, in this case patients diagnosed with Dravet syndrome, a “catastrophic early-onset encephalopathic epilepsy, with a high mortality rate

Essentially, the endocannabinoid system plays a key regulatory role in the human body. For example, there are endocannabinoid receptors in the nervous system, where cannabinoids are made locally on demand. What this means is that the nervous system sends and receives info, when this process gets out of balance, the endocannabinoid system works with those cells to maintain balance.

For example, if the receiving nerve cell becomes too excited,  seizure can surface. Seizures are due to uncontrolled electrical activity in the neurons. It’s an overstimulated state. The endocannabinoid receptor detects this overstimulation and, on demand, makes human cannabinoids to dial down the sending impulses, thereby balancing the system. 

A New Role for Endocannabinoid Signaling in Dietary Restriction and Lifespan Extension

A Study in the Journal Nature identifies a novel metabolic endocannabinoid signaling pathway in worms that coordinates the aging response to nutrient availability. There is no longer any doubt that dietary restriction (DR) extends lifespan.  Many studies have shown that limiting nutrient intake extends lifespan in yeast, worms, flies and as well as postponing age-related diseases in mice.  However, scientists are still puzzling over the exact mechanism of DR, convinced its secrets are the key to new therapies for diseases such as Alzheimer’s, Parkinson’s and even cancer.  Research involving the nematode C. elegans at the Buck Institute for Research on Aging sheds new light on a possible mechanism of DR – revealing that a group of lipid signaling molecules called N-acylethanolamines (NAEs)  informs the animal of limited or ample nutrients and helps regulate the worm’s aging response to changes in its diet. Some of these worm (NAE’s) are similar to endocannabinoids in humans, where they regulate many different physiological processes including nutrient intake and energy balance. Thus the link between endocannabinoids, DR and aging could be conserved among species.

“… most research on DR has focused on identifying individual proteins and genes that are players in the process.  Gill said this new research identifies a novel small molecule signaling pathway in the worm that coordinates how the worm responds to being in environments of limited or abundant food. “The message about nutrient availability needs to be sent to every cell in the worm’s body — those types of messages tend to be delivered by small molecules, such as hormones and lipid-derived molecules like N-acyl ethanolamines and endocannabinoids (…) Lucanic says up until this point, researchers did not think that short-lived nematode worms, used world-wide to study lifespan, had an endocannabinoid system. Even though specific endocannabinoid receptors have yet to be identified in the worm, Lucanic says there is no doubt the worm has components of an endocannabinoid system. “This research provides a new model — an easily manipulated model for researchers who are studying N-acyl ethanolamines or endocannabinoids,” said Lucanic. Endocannabinoids are active in almost every system in mammalian physiology and have been implicated in learning and memory, appetite and energy metabolism, blood pressure, inflammation and bone growth among others. However, the new research opens up the possibility that NAEs and endocannabinoids influence aging in mammals as well.  “There is a lot of interest in developing drugs that mimic the effects of DR, without patients having to reduce calories,” said Lucanic. “This research shows that endocannabinoids should be added to the list of drug targets for aging.” (39) (Source)

Conclusion:  Gill and his Buck Institute colleagues showed that NAE abundance in the worms is reduced during periods of dietary restriction, and that NAE deficiency in the presence of abundant food is sufficient to extend the animals lifespan.

Is Cannabis an essential element for the mature and elderly’s rejuvenation process ?

The answer is yes, just like with wine, the prococol should be low dose, quality stuff and taking in regularly, preferable without the puff, either via vap, food or suppository. Writing in the journal Nature Medicine, the scientists describe how they gave a month-long course of daily THC to mice aged two months, one year, and 18 months. The mice were then tested to see how fast they solved a water maze, and how quickly they recognised familiar objects such as mice they had met before.

Without the drug, the younger mice aced the tests, while the older ones struggled. But infusions of THC had a dramatic impact on both groups. The performance of the younger mice plummeted on THC, while older mice improved so much that their scores matched those of healthy drug-free young mice. The benefits lasted for weeks after the infusions ended. None of the mice displayed the strange effects one might expect from doses of THC.

“These results reveal a profound, long-lasting improvement of cognitive performance resulting from a low dose of THC treatment in mature and old animals,” the scientists write. The boost in brain function was linked to an apparent restoration of gene expression in the brain to more youthful levels.

The German team believes that the drug works by stimulating what is known as the endocannabinoid system, a biochemical pathway that becomes less active with age in mice, humans and other animals.

This and other studies therefore show that low dose cannabinoid infusion on a daily basis is the way to go insofar of the brain’s rejuvenation and the body’s general health are concerned. Adding some green tea with a little dark cacao can also potentiate the infusion. (G. Korte, A. Dreiseitel, P. Schreier, A. Oehme, S. Locher, S. Geiger, J. Heilmann, and P. G. Sand. Tea catechins’ affinity for human cannabinoid receptors. Phytomedicine, 17(1):19-22, 2010.)

Discussion

In 1973, scientists discovered that we have specific receptors in our brain for opiate drugs like heroin and morphine. These are called endogenous morphines, or endorphins, for short. They’re our natural pain relievers, released during exercise, a painful procedure, the consumption of spicy food, and orgasm.

In 1990, scientists discovered that we have specific receptors in our brain for the active ingredient in marijuana as well, cannabinoids like THC and CBD.  Here again,  it stood to reason there were natural compounds produced by our bodies that fit into those receptors.

However, with age or a life under conditions of duress and stress, many bodily functions decline, in particular the endocanabinoid system. This is why the entire Kingdom of the vertebrates and even the worms where given an endocanabinoid system so that all scientient creatures could get through Life with the maximum ease and least suffering, notwithstanding the occasional cruelty of the prey-predator evolutionary relationship.

In fact, many ECS scientists now believe the endocannabinoid system may represent the most widespread receptor system in your body. There are cannabinoid receptors in the brain, lungs, liver, kidneys, immune system, gastroentestinal system, gonads and more.The fact that the body is replete with cannabinoid receptors, key to so many biological functions, is why there’s such enormous medical potential for cannabis.  As we saw, a cannabis plant rich in THC has been shown to be a  beneficial influence on the aging brain. Rather than dulling or impairing cognition, THC appears to reverse the aging process and improve mental processes, raising the possibility it might be useful for the treatment of dementia.

How Do Plant Cannabinoids Like THC and CBD Interact with the Endocannabinoid System?

The reason that plant cannabinoids have psychoactive and medicinal effects within the body is, in large part, because we have an endocannabinoid system (ECS) that they can interact with. For example, THC gets one high because it activates the CB1 receptor within the brain. Endocannabinoids like anandamide also activate CB1. But the high is less intense and less long. That’s because the plant’s THC doesn’t interact with CB1 receptors in exactly the same fashion as the body’s natural endocannabinoids. Furthermore, the the metabolic enzymes that quickly break down endocannabinoids like anandamide don’t work on THC, so THC lingers around for much longer.

While THC is one of over 100 cannabinoids that is essential for key effects like mitigating pain, augmenting appetite and sleep, CBD is the most abundant cannabinoid, contributing up to or more than 40 percent of cannabis resin, depending on the variety. Cannabinoids produce biological effects because, just like opiates interacting with your opiate receptors, cannabinoids interact with specific receptors located in the cell membranes.

However, selectively breeding pot for high THC has diminished its medicinal value and increased its likelihood of producing adverse effects. Although research is still in its infancy, the cannabinoids appear to work in tandem with each other, balancing one another out via the entourage effect. CBD actually has anti-anxiety effects and lessens the psychoactive effects of THC. This means that a plant with a greater percentage of CBD may reduce the intensity of the effects of the THC, which in effect lowers the psychoactive potency of the plant.

Conclusion

 “…I’m not not surprised at the potential for THC to improve memory in old age (…) the key question now is does the same apply to humans? Clearly this needs to be tested, but it will not be possible in the UK due to the ridiculous restrictions on cannabis research occasioned by its being a schedule 1 drug.” (David Nutt, the former government drugs adviser and professor of neuropsychopharmacology at Imperial College London)

In summary, the ECS is a unique and ubiquitous cell-signaling system, perhaps the greatest of all of our body’s receptor network. We are still waiting for its complete genome mapping and for more experimentation.  Meanwhile, the recent identification of additional cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase.

In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few.

Since the dawn of animals, this ancient biological system  we call ECS continues willy nilly to evolve, not withstanding the State’s repression. While the ECS and its phyto-cannabinoids have shouldered animal and humankind for millions of years in their quests to be free from pain, seizures, muscle spasm without any serious side effects (38) those who have taken over the institutions of the State continue to act as if Science, the Bible, Ethics and the Constitution did not exist, they allow the sale of toxic synthetic drugs that maim and kill by the millions while incriminating on the federal level even the growing of one ganja plant or the possession of one microgram of ganja tea or the non psycho-active CBD oil.

Ch Joubert (HM Institute)

 

 

References and Precision Notes


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“Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the ‘runner’s high’, which may function to encourage habitual aerobic exercise. … Thus, a neurobiological reward for endurance exercise may explain why humans and other cursorial mammals habitually engage in aerobic exercise despite the higher associated energy costs and injury risks”
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(39). http://www.thebuck.org/buck-news/new-role-endocannabinoid-signaling-dietary-restriction-and-lifespan-extension
(40). Cannabidiol has no toxicity and it’s virtually impossible to die from marijuana. It’s also self-limiting, as excessive doses of THC will provoke anxiety, paranoia and nausea. Such side effects will disappear as the drug dissipates from your system without resulting in permanent harm, but it’ll make you think twice about taking such a high dose again. Make the same mistake with the State’s opioid, and chances are you’ll end up in the morgue
Disclaimer: Nothing in this educational blog should be construed as medical advise.
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