The G2Voice Broadcast # 146 –
What is the Endocannabinoid System in the body?
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What is the Endocannabinoid System in the body?
What is the Endocannabinoid System in the body?
We have 12+ systems in the human body! I say 12+ because science is finding many new discoveries about the human body as technology advances! Scientists believe until recently that all the stem cells were made in the bone marrow but discovered that most of the red blood cells are actually made in the lungs! The lymphatic system of the body was believed to only cover the body from the neck down with no lymphatic vessels in the brain! Well, lymphatic vessels have now been found in the brain! That only makes sense because the brain needs to eliminate toxins as does the rest of the body and this system does just that! In fact, REAL science has even found two “new organs” in the body.
For a minute there, 2018 was shaping up to be a year of new-organ discoveries. In January, Dr. J. Calvin Coffey, foundation chair of surgery at the University of Limerick, declared that he had "discovered" a new organ, dubbed the mesentery. Then, in March, fledgling science journal Scientific Reports declared the interstitium, a fluid-filled membrane that surrounds the lungs, digestive tracts and arteries, an organ as well. If verified by the rest of the medical community, these findings could potentially revolutionize our understanding of the human body. There's only one problem with that: These biological structures aren't actually organs.
Whether these discoveries are organs or not doesn’t really matter. The point I am trying to make is; how much do we really understand about the human body and what other surprises will be found as technology changes?
What we do know is that the human body is amazingly complex and orderly just as the Bible reveals to us for thousands of years! Without acknowledging the Creator’s design in ALL creation, the world won’t find the TRUTH!
There is no wisdom nor understanding nor counsel against the Lord.
13 For thou hast possessed my reins: thou hast covered me in my mother's womb.
14 I will praise thee; for I am fearfully and wonderfully made: marvellous are thy works; and that my soul knoweth right well.
15 My substance was not hid from thee, when I was made in secret, and curiously wrought in the lowest parts of the earth.”, Psalm 139:13-15 King James Version (KJV)
Let’s look at what we know about the ECS of the body and you decide if it is complex, needed and was designed for a reason, in fact, many reasons!
How the Endocannabinoid System was Discovered
Currently, in the United States, forty-six states and three territories have some form of a medical cannabis program. This has been a long struggle for advocates, however. Ever since the inception of the Marijuana Tax Act of 1937 that effectively banned its use and sale, which was later replaced with The Controlled Substances Act in 1970, it has been a slow process in the discovery of how cannabis interacts with mammalian bodies. Scientists discovered the brain's opiate receptor in 1973, but it was not until 1988 in a government-funded study at the St. Louis University School of Medicine that Allyn Howlett and William Devane determined that the mammalian brain has receptor sites that respond to compounds found in cannabis. These receptors, named cannabinoid receptors turned out to be the most abundant type of neurotransmitter receptor in the brain.
Although the legal stature of cannabis as a schedule 1 narcotic slowed research, it did not prevent it. The U.S. government put forth funding toward cannabis research in hopes that it might produce evidence to support the claims of its deleterious effects, and throughout the decade of the nineties, many discoveries occurred, within the states, and across the seas. In 1990, it was announced that a team lead by Lisa Matsuda at the National Institute of Mental health had mapped the DNA sequence that encodes a cannabinoid receptor in the brain. Matsuda was also able to clone this receptor. This opened doors and lead to the development in knockout mice that lacked the G-coupled protein receptor. When THC was administered to the knockout mice it was shown that THC had no effect, proving THC works by activating cannabinoid receptors in the brain.
A second cannabinoid named CB2 was also identified at this time, which takes presence throughout the immune system and the peripheral nervous system. The discovery of these receptors resulted in the uncovering of naturally occurring neurotransmitters called endocannabinoids. In 1992, at the Hebrew University in Jerusalem, Dr. Lumir Hanus along with American researcher Dr. William Devane discovered the endocannabinoid anandamide. The same team later discovered a second-major endocannabinoid 2-arachidonoylglycerol (2-AG) and went on to uncover the less known endocannabinoids; homo-gamma-lineleoul ethanolamide, docosatetraenoul ethanolamide (DEA), and noladin ether (2-AGE). Including N-arachidonoyldopamin (NADA), there are over a handful of endocannabinoids that have been identified, along with another handful of G- coupled protein receptors that interact with these endocannabinoids.
In the pursuit of unearthing the metabolic pathways of phytocannabinoids and endocannabinoids, scientists came across an unknown molecular signaling system within the body that is involved in regulating a broad range of biological functions. This system was named the endocannabinoid system (ECS). The ECS performs multiple tasks, but the goal is always to maintain a stable environment despite fluctuations in the external environment. It is the system that creates homeostasis within the body. When an imbalance is detected within our internal environment, the body synthesizes endocannabinoids that interact with the cannabinoid receptors. This stimulates a chemical response that works to return the physiological process back to homeostasis. However, in some cases, there is a deficiency in ECS signaling. This condition is known as Clinical Endocannabinoid Deficiency. Reasons to as why this condition occurs ranges from our body not synthesizing enough endocannabinoids, our bodies not producing enough cannabinoid receptors, an abundance of enzymes that break down cannabinoids, or outside sources such as foods and medications that decrease ECS signaling. The phytocannabinoids contained in cannabis can be used to supplement this deficiency. By stimulating and supporting your endocannabinoid system one can find relief from a multitude of illnesses and conditions.
Cannabis in the human body
There are many examples of the use of medicinal cannabis throughout history from Biblical times and ancient Egypt, through to the reign of Queen Victoria. Until the 1930's, the plant itself and medicines which contained extracts of it, were an integral part of the global pharmacopoeia. Laboratory research and clinical studies conducted in Israel since the 1964, has significantly promoted worldwide awareness and understanding of the therapeutic possibilities of the cannabis plant.
The main active compounds in the cannabis plant are called cannabinoids. In addition to studying the plant, the human body’s response to cannabis has also been of interest to scientists and they’ve discovered that the active ingredients found in cannabis play important and unique roles in human health. The plant substances that stimulate cannabinoid receptors and that can be found in cannabis plants are called Phytocannabinoids. The most famous cannabinoid is THC or Delta-9-tetrahydrocannabinol which is also the most psychoactive. Other cannabinoids such as cannabidiol (CBD) and cannabinol (CBN) are also being studied so that researchers can unlock the secrets of their healing properties.
As research has progressed, scientists have discovered some of the ways cannabinoids affect the human body and even discovered that human beings have a special bodily system called the endocannabinoid system. The discovery of the endocannabinoid system and the study of its functions in the body was pioneered by Professor Rephael Mechoulam from the Hebrew University of Jerusalem. Professor Mechoulam’s research has aided in opening up a new area in biochemistry and the study of the brain related to cannabis.
“The endocannabinoid system has been studied using genetic and pharmacological methods. These studies have revealed that cannabinoids act as neuromodulators for a variety of physiological processes, including motor learning, synaptic plasticity, appetite, and pain sensation." ibid
Cannabinoid receptors are believed to be more numerous than any other receptor system and have been discovered throughout the body. The stimulation of cannabinoid receptors causes a variety of physiologic processes. Researchers have identified two cannabinoid receptors. The first receptor discovered – CB1 – is found mainly in the brain but in recent years has also been found in peripheral tissue.
The second receptor identified - CB2 – manifests almost exclusively in cells and organs connected with the immune system and cardiovascular system, its highest concentration being found in the spleen. It is responsible for the anti-inflammatory properties of Cannabis. Many parts of the body contain both CB1 and CB2 receptors and there may be others waiting to be discovered.
Research has shown that cannabis has a significant role in the human body in many different areas including: memory, appetite, pain sensation, stress response, energy balance and metabolism, anxiety, immune functions, thermoregulation, sleep and other systems.
The endocannabinoid system is responsible for complex interactions in the immune system, nervous system, and all of the body’s organs and can be understood as a bridge between the mind and body.
What Is The Endocannabinoid System?
In 1964, researchers in Israel discovered the therapeutically active substances in marijuana that have come to be called cannabinoids and isolated the most popular and possibly effective cannabinoid, THC (tetrahydrocannabinol). More than 20 years later, in 1988, researchers identified the human body’s endocannabinoid system.
Endocannabinoids are the special molecules naturally produced in the human body that are closely related to proper functioning of the immune system and nervous system and that are mimicked by the cannabinoids found in the marijuana plant. Cannabinoids contained in marijuana, referred to as phytocannabinoids, simply imitate endocannabinoids. Cannabinoids fit perfectly into specialized receptors found throughout the nervous and immune systems, serving to enhance, or improve upon, the body’s own ability to maintain homeostasis (balance) and health.
The Role of Receptors
Research since the discovery of the endocannabinoid system has led to the identification of specialized receptors in the body. Knowledge of these receptors, called CB1 and CB2, has greatly enhanced the overall knowledge of how cannabinoids synergistically interact with other cannabinoids and endocannabinoids to produce sometimes profound medical effects. An understanding of these receptors also allows for the production of synthetic cannabinoids and specialized extracts that best take advantage of the function of these receptors.
CB1 receptors are located throughout the brain and central nervous system, as well as the kidneys, liver, lungs, digestive tract, and even the eyes. Revealingly, these receptors outnumber those for opiates by a wide margin (possibly as high as 10 to 1). The placement of CB1 receptors is also why overdoses on marijuana are impossible – because these receptors are not present in the basal regions of the brain that are responsible for vital functions, such as heart and respiratory function, overdoses due solely to marijuana use simply do not occur.
CB2 receptors are primarily found in the peripheral organs, in particular tissues associated with the immune system, including the tonsils, thymus, spleen, and bone marrow.
An Expert’s Explanation
Dr. Ethan Russo, a prominent and well-published cannabinoid researcher, has written a detailed description of the endocannabinoid system and its efficacy for human health:
“The analgesic and palliative effects of the marijuana and cannabinoid preparation have been amply reported over the past generation…. In essence, the effects result from a combination of receptor and non-receptor mediated mechanisms. THC and other cannabinoids exert many actions through cannabinoid receptors, G-protein coupled membrane receptors that are extremely densely represented in central, spinal, and peripheral nociceptive pathways.”
“Endogenous cannabinoids (endocannabinoids) even regulate integrative pain structures such as the periaqueductal gray matter. The endocannabinoid system also interacts in numerous ways with the endogenous opioid and vanillio systems that can modulate analgesia and with a myriad of other neurotransmitter systems such as the serotonergic, dopaminergic, glutameatergic, etc, pertinent to pain. The current author has suggested that a clinical endocannabinoid deficiency may underlie the pathogenesis of migraine, fibromyalgia, idiopathic bowel syndrome, and numerous other painful conditions that defy modern pathophysiological explanation or adequate treatment.”
Meet Your Endocannabinoid System: The Center of Well Being
The Magazine: Meet Your Endocannabinoid System: The Center of Well Being
It’s one of the most important systems in the body. And yet, it’s one that has only recently begun to be studied and understood. Here’s a look at the basics of the ECS and why further research is so important.
What exactly is the Endocannabinoid System?
Found throughout the brain, nervous systems and organs of humans and all mammals — birds, fish and reptiles, too — the
Endocannabinoid System (ECS) is the body’s internal system of cannabis
molecules and receptors. Native and primitive, scientists predict that humans evolved to possess this system over 500 million years ago.
Why is the ECS important to our well being?
The ECS is the largest biological system of receptors in the body, and some scientists believe it is the most important physiological system involved in establishing and maintaining human health. Its job is to maintain
, or balance, and to keep our cells and immune system healthy.
What is the ECS made up of?
- Endocannabinoids: activate cannabinoid receptors
- Cannabinoid Receptors: mediate the effects of cannabinoids
- Enzymes: help the body break down and recycle endocannabinoids
What are the two main receptors within the ECS?
- CB1: regulates appetite and memory and reduce pain, found in the brain and spinal cord
- CB2: works to reduce inflammation, found in the immune system and other areas of the body
What are Endocannabinoids?
Endocannabinoids are cannabinoid-like molecules naturally produced by cells in our body. Endocannabinoids and receptors make up the ECS and exist throughout the body in the brain, immune cells, organs, glands and connective tissues. When something brings a cell out of balance, the ECS is often called upon to restore the previous physiological situation, thus maintaining homeostasis. As a result, our bodies are constantly producing endocannabinoids to address imbalances.
What are the two main endocannabinoids naturally produced inside the body?
- 2-AG: the most prevalent endocannabinoid, responsible for managing appetite, pain response and immune system function
- Anandamide: named after “Ananda,” the Sanskrit word for “bliss” and “happiness, considered “the bliss molecule” and is responsible for the blissful state cannabis induces
What is endocannabinoid system deficiency?
Growing research suggests that a deficiency of endocannabinoids in the body may be linked to specific health issues. Endocannabinoid System Deficiency is a theory for the symptoms and conditions that develop when the Endocannabinoid System isn't functioning properly, or when there aren't enough endocannabinoids present in the body. While we still need more research to fully understand the impact of
, we do understand the importance of a healthy Endocannabinoid System to maintain health and support homeostasis.
Why is homeostasis good?
The ECS has one goal in mind: homeostasis. Throughout changes in our external environment, such as temperature, stress, inflammation or harmful chemical exposures, our ECS works to maintain a stable internal environment. By working to achieve homeostasis, the ECS regulates the many functions necessary for survival and ensures that the body is stable and works in harmony.
How are the ECS and the cannabis plant related?
For the longest time, we didn’t understand why cannabis affected humans. It wasn’t until the 1990’s that scientist Dr. Raphael Mechoulam discovered the Endocannabinoid System in his laboratory at the Hebrew University in Israel. Together with his team, Dr. Mechoulam uncovered naturally occurring neurotransmitters (called endocannabinoids) that are almost identical in structure to the compounds produced by the cannabis plant (called
.) From here, we uncovered the active compounds in hemp and
and we are just beginning to understand how they impact human health.
What are Phytocannabinoids?
Phytocannabinoids are naturally-occuring cannabinoids found in the hemp and marijuana plants. Science suggests that the most effective way to support our ECS is by ingesting phytocannabinoids. Hemp and marijuana are the only plants in the world that produce cannabinoids. There are 120 known phytocannabinoids in cannabis and the majority are understudied and not properly understood.
Cannabinoids are known antioxidants and neuroprotectants, as proven by the U.S. Government’s patent (Patent 6630507B1) stating that “cannabinoids have been found to have antioxidant properties and are found to have particular application as neuroprotectants or in the treatment of neurodegenerative diseases.”
The two main phytocannabinoids are CBD and THC. How are they different and how do they work?
CBD and THC are the two most well-known cannabinoids found in the hemp and marijuana plants. THC, present in high levels in the marijuana plant, is the only known intoxicating cannabinoid, responsible for “the high.” THC binds to the
CB1 and CB2 receptors in the body to reduce inflammation, also affecting appetite and other essential body functions. CBD, present in high levels in the hemp plant doesn’t directly bind to CB1 or CB2 receptors — scientists believe that CBD may prevent the breakdown of naturally occurring endocannabinoids in the body.
How do cannabinoids regulate our mental health?
Emotional health is just as important as physical health in overall body harmony, and endocannabinoids are considered “literally a bridge between body and mind,” With ECS receptors present in the brain and throughout the body, phytocannabinoids help to regulate emotional functions like mood and stress response. And, preliminary studies show that cannabinoid-based therapies may be helpful in anxiety and mood disorders.
What can we do to advance cannabis research to support our ECS and therefore, our health?
Regulatory complexities have made it difficult for U.S. scientists to conduct meaningful research and clinical trials with cannabis. However, academic institutions like UCLA, UC Davis, UC San Diego, UCSF and others are taking initiative to pioneer medical cannabis research. The UCLA Cannabis Research Initiative, led by Dr. Jeff Chen, is currently conducting multiple cannabinoid studies that are made possible through private donations. Until regulations change, it is up to us to do what we can to support cannabis research and further the collective understanding of the ECS.
How Moses and the Israelites Used Cannabis
- For the Bible tells me so.
They don’t teach you in Sunday school that cannabis appears in the Old Testament but modern scholarship shows that cannabis was used sacramentally by Moses and the ancient Israelites. Cannabis appears by name five times in the original Hebrew text of the Bible according to research by Polish etymologist Sula Benet, whose work Chris Bennett later expanded on. The Hebrew word “kaneh bosm” is cannabis but was later mistranslated as other plants including calamus or aromatic cane.
The Old Testament tells the story of Jewish history and how over a thousand-year period the worship of the single Israelite god ultimately took hold over the indigenous polytheistic culture. The ancient Israelites at the time of Moses in 1500 BCE lived in the land of Canaan (modern day Israel and Palestine) among the broader Canaanite culture that worshipped the Mother Goddess and many gods.
Cannabis was well established in the region and had been used for thousands of years as fiber, food, ganja, and incense. In the early centuries of the Bible the Lord favors cannabis as the Hebrew culture was still Canaanite, but over time as the worship of the Mother Goddess is purged practices such as burning incense to her in the temple are purged as well.
The first and most significant reference to cannabis is in the story of Moses, where God gives him specific instructions for how to properly set up the Tabernacle for worship and includes a recipe for holy anointing oil that includes cannabis. The holy anointing oil was to be used to anoint the temple and the priests and is sacred, the recipe not to be shared.
Exodus 30: 23-25: 1446 BCE
“Then the Lord said to Moses, ‘Take the following fine spices: 500 shekels of liquid myrrh, half as much (that is, 250 shekels) of fragrant cinnamon, 250 shekels of fragrant calamus [cannabis], 500 shekels of cassia—all according to the sanctuary shekel—and a hin of olive oil. Make these into a sacred anointing oil, a fragrant blend, the work of a perfumer. It will be the sacred anointing oil.’”
Converted into today’s measurements:
- Liquid myrrh 500 shekels 5.75 kg (12.68 lbs)
- Cassia 500 shekels 5.75 kg (12.68 lbs)
- Cinnamon leaf 250 shekels 2.875 kg (6.34 lbs)
- Cannabis flowers 250 shekels 2.875 kg (6.34 lbs)
- Olive oil 1 hin 6.5 liters (1.72 gallons)
As you can imagine, an oil that contains more than 6 pounds of ganja steeped in less than 2 gallons of olive oil is going to be very potent. In ceremonies the oil would be poured over the head and body of the priest, drenching them. The skin readily absorbs THC and the effect of soaking in this oil would be very psychoactive, offering some serious communion with the Lord.
The second reference to cannabis is in the court of King Solomon, who ruled in the 10th century BCE. Solomon was known for his great wisdom and he built the first Hebrew temple in Jerusalem. But unlike his father, King David, Solomon fell out of favor with the Lord because King Solomon worshipped Asherah, the Canaanite goddess of his wives and he burned incense to her.
Solomon also wrote the Song of Songs (also known as the Song of Solomon), a love poem that is considered the most beautiful text in the Bible and unique for being explicitly sexual. In chapter 4 the man describes the beauty of his lover, comparing her to the most beautiful flowers, including cannabis, among other flattery.
Song of Songs 4: 10-15 950 BCE
“How delightful is your love, my sister, my bride! How much more pleasing is your love than wine, and the fragrance of your perfume more than any spice! Your lips drop sweetness as the honeycomb, my bride; milk and honey are under your tongue. The fragrance of your garments is like the fragrance of Lebanon. You are a garden locked up, my sister, my bride; you are a spring enclosed, a sealed fountain. Your plants are an orchard of pomegranates with choice fruits, with henna and nard, nard and saffron, calamus [cannabis] and cinnamon, with every kind of incense tree, with myrrh and aloes and all the finest spices. You are a garden fountain, a well of flowing water streaming down from Lebanon.”
As the tale of Jewish history moves on to the 8th century BCE and the prophet Isaiah, cannabis once again makes an appearance. Isaiah warned about the sinfulness and faithlessness of Israel and preached reform. Cannabis is referenced in the text as one of the offerings the Israelites have failed to bring to the Lord.
Isaiah 43:24 711 BCE
“You have not bought any fragrant calamus [cannabis] for me, or lavished on me the fat of your sacrifices. But you have burdened me with your sins and wearied me with your offenses.”
The fourth reference to cannabis comes in the book of Jeremiah, where God is angry with the Israelites for their greed and deceit. Jeremiah was known as the weeping prophet who foresaw the coming destruction of Israel. In the passage, cannabis is referenced as among the offerings God rejects, reflecting a definitive shift in worship practices.
Jeremiah 6:20 627 BCE
“What do I care about incense from Sheba or sweet calamus [cannabis] from a distant land? Your burnt offerings are not acceptable; your sacrifices do not please me.”
In 586 BCE comes the fall of Jerusalem and the Babylonian exile. This is one of the most traumatic and important chapters in Jewish history. Tyre, in modern day Lebanon, was the wealthy capital city of Canaan and also besieged by the Babylonians. Cannabis is listed among the items of trade that passed through the great city in the fifth explicit reference to the plant.
Ezekiel 27:18-19 586 BCE
“Damascus did business with you because of your many products and great wealth of goods. They offered wine from Helbon, wool from Zahar and casks of wine from Izal in exchange for your wares: wrought iron, cassia and calamus [cannabis].”
Cannabis is ultimately rejected by the Israelites once and for all during the time of Babylonian exile along with the worship of the Mother Goddess Asherah, the Queen of Heaven. There is a long passage in Jeremiah where the prophet rails against Asherah while the women defend their practice of burning incense to her. I think we all know who won that conflict.
Jeremiah 44:15-23 588 BCE
“Then all the men who knew that their wives were burning incense to other gods, along with all the women who were present—a large assembly—and all the people living in Lower and Upper Egypt, said to Jeremiah, ‘We will not listen to the message you have spoken to us in the name of the LORD! We will certainly do everything we said we would: We will burn incense to the Queen of Heaven and will pour out drink offerings to her just as we and our ancestors, our kings and our officials did in the towns of Judah and in the streets of Jerusalem. At that time we had plenty of food and were well off and suffered no harm. But ever since we stopped burning incense to the Queen of Heaven and pouring out drink offerings to her, we have had nothing and have been perishing by sword and famine.’”
The women added, “When we burned incense to the Queen of Heaven and poured out drink offerings to her, did not our husbands know that we were making cakes impressed with her image and pouring out drink offerings to her?”
Then Jeremiah said to all the people, both men and women, who were answering him, “Did not the Lord remember and call to mind the incense burned in the towns of Judah and the streets of Jerusalem by you and your ancestors, your kings and your officials and the people of the land? When the Lord could no longer endure your wicked actions and the detestable things you did, your land became a curse and a desolate waste without inhabitants, as it is today. Because you have burned incense and have sinned against the Lord and have not obeyed him or followed his law or his decrees or his stipulations, this disaster has come upon you, as you now see.”
The endocannabinoid system: Here’s how it keeps the body healthy and happy
The endocannabinoid system consists of cellular receptors found in very large amounts throughout the body
In order to consume medical cannabis in a responsible and efficient manner, a person should completely understand what exactly goes on in the body upon introducing it the active molecules from the cannabis plant. The way these cannabis-derived compounds interact with our organism is astonishing.
The endocannabinoid system consists of cellular receptors found in very large amounts throughout the body, and the endocannabinoids—the body’s internal chemical compounds that entice these endocannabinoid receptors.
- How to vape cannabis for beginners
- Highest THC strains: What are the strongest strains in 2018?
- How to deal with memory loss and other negative effects of cannabis
Because this is such a complicated topic, wrapping one’s head around everything requires some patience and dedication. However, fathoming the endocannabinoid system is really rewarding and extremely beneficial to anyone looking to consume cannabis for healing purposes.
It should be taken into consideration that the science of cannabis still has a long way to go, and because of this there are some blanks waiting to be filled. The almost century-long, worldwide illegality of this plant should be held, in large part, accountable for the limited body of research today, and the reasons that led to banning cannabis are also quite sketchy and play a role.
Nonetheless, the available collection of scientific works confirms that consuming cannabis-derived cannabinoids compels the body to produce more endocannabinoid receptors, but also to create additional quantities of internal endocannabinoids.
Both endocannabinoids from the body, and the cannabinoids from the cannabis plant activate cell receptors that cause that individual cell to react in a certain way, and this reaction is dependent not only on the type of cell activated through these receptors, but also on the condition the body is struggling with at the time.
This may sound like science fiction, but exploring the science behind the endocannabinoids system will help make all this much more understandable. Let’s start with checking out the most notable aspects of the topic.
- What exactly is the endocannabinoid system, its purpose and when was it discovered?
- What are the main types of cellular receptors within the endocannabinoid system?
- What are the main types of endocannabinoids and how they influence the endocannabinoid system?
- What is endocannabinoid system deficiency?
Role of the endocannabinoid system
First, the endocannabinoid system, also known as the ECS, is a vast “network” comprised out of the following:
- Cellular cannabinoid receptors: These receptors are located on the membranes of many different cells found throughout the body.
- Endocannabinoids: These active signaling molecules produced by the body are structurally very similar to active compounds found in cannabis. These internal cannabinoids—just like the ones from cannabis—activate the cannabinoid receptors, and by doing this, trigger a specific response from a cell.
- Enzymes: Different enzymes are responsible for the creation (synthesis), and later the degradation of these compounds.
What’s truly amazing about the endocannabinoid system is that the cells that express these specialized endocannabinoid receptors are located in all of the most important parts of our body, including the following:
- the central nervous system (brain, spinal cord);
- all vital organs;
- The reproductive organs
- various glands;
- the immune system;
- the gastrointestinal tract; and
- connective tissues.
So, the body has this extremely widespread network of cell receptors that react to endocannabinoids and cannabinoids, but what is the function of this system?
The sole purpose of the ECS is to maintain balance within an organism. This is achieved by performing different tasks within an individual cell, because depending on what type of cell it is—nerve cells, immune cells, skin cells, muscle cells, secretory cells and so forth—the precise mechanism of action of that specific cell will be different.
The way a specific cell reacts when a endocannabinoid (or a cannabinoid) activates its receptor is also dependent on the type of condition with which an organism is afflicted. This means the ECS is very adaptive and can trigger an extremely wide range of biological responses inside of a single cell, depending on what exactly is wrong at that given time.
In an ideal situation, where all the systems of the body—including the circulatory, digestive, endocrine, integumentary/exocrine, lymphatic/immune, muscular, nervous, urinary/excretory, reproductive, respiratory and skeletal—function optimally, this perfect functioning of an organism is called the homeostasis, which can be also understood as a dynamic state of equilibrium. The endocannabinoid system is a primary “instrument” in charge of maintaining homeostasis, and this is why the cells of all these different systems and tissues have (endo)cannabinoid receptors.
In a nutshell, the endocannabinoid system oversees maintaining health on a cellular level in every system of the body, vigilantly reacting and adapting to the continuous changes that the body encounters.
Unfortunately, the ECS does not function properly in everyone, and this malfunction is associated with the body’s inability to heal itself optimally. Even though the precise causes of ECS malfunction remain elusive, it is hypothesized that numerous different factors—including genetics, diet, lack of exercise, various pollutants and stress—are all responsible for an insufficiently effective endocannabinoid system.
An inactive ECS can also be responsible for “helping” some conditions and diseases to occur, which the article will later address.
Endocannabinoid system discovery
Uncovering how the cannabinoids from cannabis, and the internal endocannabinoids, stimulate the cellular receptors across the body was not a simple task.
Over the course of history, numerous cultures have been using cannabis for medicinal reasons. During the 19th century, cannabis-derived products were also used for health-related purposes across Europe and the U.S. because of the pioneer work of Williams O’Shaughnessy, a doctor from Ireland, and French scientist Jacques-Joseph Moreau.
As the science of chemistry wasn’t fully developed, they only understood that cannabis brings relief for numerous conditions, without comprehending how the healing actually occurs.
Consider the brief, but precise, timeline of scientific discoveries in the field of cannabis:
- 1895: the first cannabis-based compound named cannabinol (CBN) was isolated;
- 1930: the precise chemical structure of cannabinol (CBN) was mapped;
- 1940: the second cannabis-based compound cannabidiol (CBD) was isolated;
- 1963: the precise chemical structure of cannabidiol (CBD) was mapped;
- 1964: the psychoactive tetrahydrocannabinol (THC) was isolated;
- 1988: the cannabinoid receptors were first located;
- 1990: a cannabinoid receptor was first cloned; and
- 1993: internal endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were first identified.
As can be seen, discoveries over the last three decades include the identification of both the cannabinoid receptors and the endocannabinoids, discoveries that are absolutely crucial for understanding how the endocannabinoid system functions, and how the cannabinoids from the cannabis plant affect and influence this system.
Through all these years, numerous scientists gave their contributions to help reveal the secrets of cannabis and the ECS, but the person who improved the science behind cannabis the most is Dr. Raphael Mechoulam, a famed Israeli organic chemist and a professor of medicinal chemistry in Jerusalem. Mechoulam was involved in mapping the structure of CBD in 1963, and one year later, he and his team identified and isolated THC. During the 1990s, he also participated in the discovery of the body’s own endocannabinoids anandamide and 2-AG.
Learn more about his magnificent work in our article on THC.
The ECS was discovered by accident, so to speak. In the 1980s, researchers were trying to uncover how cannabis, more precisely THC, induces the psychoactive high, and found that certain cells in the body have specific cellular receptors, in which THC fit perfectly.
Researchers theorized the body must produce its own endogenous compounds that are structurally similar to THC, and after several years of research, more precisely in 1993, anandamide and 2-AG were identified.
By discovering the endocannabinoid receptors and internal endocannabinoids, scientists have confirmed the existence of a previously unknown physiological system. It is now known that the ECS has an incredibly beneficial influence on practically every other system in the body, and functions as a tool for healing, but also for maintaining optimal health.
Below are a few interesting facts about the ECS in general:
- besides humans, every other vertebrate species (animals with a spine) possess an endocannabinoid system;
- the most primitive animal that expresses an ECS is the sea-squirt (also called tunicate), which evolved around 600 million years ago; and
- in humans, a 2009 study shows the endocannabinoid system is fully operational before leaving the mother’s uterus.
Receptors of the endocannabinoid system
These cellular receptors are responsible for the body’s reaction to endocannabinoids, but also the cannabinoids from cannabis. There are two main, distinct types of cannabinoid receptors, and they can be considered “locks” present on the membranes of different types of cells in the body. The endocannabinoid and cannabinoid compounds, for their parts, act as “keys” that trigger a specific response from these cells, upon entering the “lock” of the receptors.
CB1s are the most abundant cannabinoid receptors in the body and are mostly located in the central nervous system (CNS), more precisely the brain and the spinal cord. In the brain, the largest quantity of the CB1 receptors is present in the following:
- frontal cortex: where thinking happens;
- hippocampus: in charge of memory;
- cerebellum: in charge of movement; and
- basal ganglia: associated with voluntary movement, learning, cognition and emotion.
Other than the central nervous system, CB1 receptors are found in the vital and reproductive organs, various glands, gastrointestinal and urinary tract, white blood cells and connective tissues.
CB2 is the second most prominent cannabinoid receptor, and unlike CB1, it is mostly found in the gastrointestinal (GI) tract, where most of the body’s immune system is located. Large concentrations of CB2 receptors are also found in the tonsils and the thymus gland, and both sections of the body are also valuable assets of the immune response. Like CB1, CB2 receptors are expressed in some neuron cells, like the microglia, in the brain and other parts of the central nervous system, but in much smaller quantities.
Another captivating attribute of the ECS is that both the cannabinoid receptors and the internal endocannabinoids get synthesized in the body on demand. This basically means that when the body “senses” that additional receptor/endocannabinoid expression will return the organism into a state of homeostasis, both the receptors and the compounds get synthesized on demand.
Studies, including one published in 2007, have shown that this trait of the ECS occurs in situations like nerve injury, inflammation and tissue damage. Here are a few more facts about ECS receptors:
- It is speculated that CB1 and CB2 receptors are more numerous than any other receptor system in the human body, including the receptors of neurotransmitters dopamine and serotonin.
- Numerous parts of the body contain both CB1 and CB2 receptors, and they are found on many intersections—the borders of two or more different physiological systems—of the body, contributing to the communication and co-operation of differing types of cells.
- Besides CB1 and CB2, certain endocannabinoids activate other receptors in the body, including the transient receptor potential (TRP) and peroxisome proliferator activated receptors (PPARs).
Very similar to the current understanding of cannabis-derived cannabinoids, contemporary science has currently figured out the precise mechanisms of action of two internal endocannabinoids, anandamide and 2-AG. Even though not everything is understood, the ongoing research has provided great insight about the functioning of the ECS, and the extremely diverse roles of these endogenous compounds.
Anandamide (N-arachidonoylethanolamine, or AEA)
Discovered in 1993 by Mechoulam, anandamide is the most thoroughly studied endocannabinoid. The name is derived from the sanskrit word “ananda”, meaning bliss or delight, which is one of the main cerebral effects of anandamide.
The role of this compound is profoundly diverse, helping to regulate numerous processes that include immune system function, central nervous system function, appetite, pain, memory and much more. Anandamide is an activator, or agonist, of both CB1 and CB2 endocannabinoid receptors, meaning it is created (synthesized) throughout the tissues of the body, which also explains its divergent effect on the organism.
As previously mentioned, both endocannabinoids and endocannabinoid receptors get synthesized on demand, meaning the body makes them once it “senses” the need for these compounds.
Exercise boosts anandamide levels
The best example of this phenomena is the “runner’s high”, where long-distance runners experience an intensely visceral euphoric feeling, and this sensation is actually anandamide’s doing. Scientists have observed that prolonged aerobic exercise, for over 30 minutes, increases anandamide levels, complementing the joyous feeling experienced after hard physical labour. Marathon and triathlon competitors, for example, experience increased levels of anandamide in the greatest possible extent as their aerobic exercise is intense and very durable at the same time.
Anandamide affects memory and forgetting
What’s also fascinating is the effect that anandamide has on memory. Naturally, one would assume that it increases or enhances memory, but the truth is, this compound has a very important role in forgetting.
This might seem somewhat unusual at first but consider how much input humans receive from their senses daily. For instance, the amount of faces seen every time as a person, for example, rides the subway. For the brain to store things worth remembering, unneeded information has to be “deleted”.
Anandamide’s so-called forgetting function is also very important for traumatic and extremely stressful events, and people suffering from post-traumatic stress disorder (PTSD) have a very difficult time disconnecting from the trauma they’ve experienced. This is why CBD works wonders for anxiety and also PTSD patients.
As noted previously, endocannabinoids are created and degraded by certain enzymes in our body. Cannabidiol (CBD) lessens the production of a specific enzyme that is responsible for degrading, or “recycling”, anandamide. By diminishing the amounts of the FAAH (fatty acid amide hydrolase) enzyme, anandamide is left to engage the receptors of the endocannabinoid system for extended periods of time, leading to a diminishment of general anxiety, but also the stress caused by PTSD.
Genetic mutations increase anandamide levels
The exact same mechanism of degrading anandamide with FAAH enzyme is also what separates entire happy from unhappy nations, which was noticed by examining their “levels of happiness.” This research provided an insight that specific genetic mutations are responsible for different levels of FAAH enzyme in the body, and lesser quantities of this enzyme directly correlates with a constantly better mood, and a general sense of well-being.
The science team behind this study also noted that a sense of happiness, of course, isn’t only dependant on this connection, but also depends on a complex mixture of economic and political factors.
Foods that increase anandamide production
Some foods are can actually boost anandamide levels, and some can slow down the metabolization of the FAAH enzyme that degrades it.
Pure chocolate affects anandamide levels in two ways: First, it increases the number of available endocannabinoid receptors that can be triggered by anandamide and, second, it diminishes levels of FAAH enzyme that destroys it.
Unlike chocolate, which influences the ECS in more subtle ways, black truffles contain the anandamide compound, and when eaten, they directly increase the levels of this endocannabinoid in the body.
What’s also fascinating about these mushrooms is that they don’t have any endocannabinoid receptors whatsoever, and it is theorized the presence of anandamide acts as a tactic for spreading the spores—their asexual reproductive units—by attracting predators to eat them, and, subsequently, spreading the spores to nearby surfaces.
This compound is found in many fruits and vegetables, such as apples, grapes, onions, potatoes, tomatoes and broccoli. Besides being a powerful antioxidant and reducing oxidative stress, kaempferol also inhibits the synthetization of FAAH enzyme, thus prolonging the duration and effect of anandamide.
Omega 3 Fatty Acid
Consuming these polyunsaturated fatty acids found in fish oil, krill oil, hemp and flax seeds has been shown to increase the vigilance of the endocannbinoid system.
This is the second most prominent endocannabinoid found in the body, but currently it isn’t nearly as researched as anandamide. What is known so far is that 2-AG is present in much larger quantities in the central nervous system—brain and spinal cord—than anandamide. 2-AG is also an agonist—it triggers a biological response—of both CB1 and CB2 endocannabinoid receptors.
What’s also interesting is that 2-AG is a high-efficiency agonist of endocannabinoid receptors, while anandamide is described as a low-efficiency agonist for CB1, and a very low-efficiency agonist of CB2 receptors.
What additionally separates anandamide and 2-AG is that the enzymes that synthesize and degrade these endocannabinoids are completely different—anandamide is degraded by FAAH, and 2-AG is degraded by an enzyme called monoacylglycerol lipase (MAGL).
As such, they have completely different roles within the ECS, although both are tools for maintaining balance within an organism, which is the primary function of the endocannabinoid system.
Researchers will, undoubtedly, provide additional knowledge about this enigmatic compound soon.
Endocannabinoid system deficiency
Clinical endocannabinoid deficiency, or CECD, is a health condition where the body doesn’t produce adequate quantities of endocannabinoids, or it doesn’t produce the needed amount of endocannabinoid receptors. A possible cause for CECD be that the body produces too many enzymes (FAAH, MAGL), that break down the endocannabinoids before they get the chance to affect the receptors. As a result of this deficiency, a weakened ECS cannot properly maintain homeostasis.
The condition was first described by Dr. Ethan Russo, who’s been on the forefront of modern cannabis research during the last two decades. Russo’s research shows that clinical ECS deficiency can have a negative influence on many conditions and diseases, including the following:
- irritable bowel syndrome (IBS);
- post-traumatic stress disorder (PTSD);
- multiple sclerosis;
- Parkinson’s disease;
- chronic pain;
- muscle spasms; and
- mood imbalances and irritability.
Cannabis is a valid and successful treatment method for so many conditions, including anxiety KatarzynaBialasiewicz / iStock / Getty Images Plus
All of this may seem a bit far-fetched to someone who isn’t acquainted with the incredibly diverse role that the ECS plays in the body. But if official scientific research concluded that a malfunctioning endocannabinoid system is connected to so many physiological issues, this directly coincides with why cannabis is a valid and successful treatment method for so many conditions, disorders and diseases, such as the following:
Combating skepticism through awareness
Even though the number of scientific studies dealing with medical cannabis, endocannabinoid system and cannabinoids from cannabis have already been the subject of over 24.000 different articles, many people are still very skeptical about the healing properties of this plant. Considering the decades-long global illegality of cannabis, this doesn’t really come as a surprise. Taking one’s health into one’s own hands is something I consider a personal responsibility, especially when the medicine in question is something completely natural and has existed on this planet long before humans.
Another reason that demands self-education about cannabis and health is that very few doctors know anything about the ECS, and the effects of endocannabinoids and cannabinoids.
This survey from 2013 was conducted by the Medical Cannabis Evaluation. It questioned medical schools in the U.S. if the endocannabinoid system is a part of their curriculum.
The survey found that only 13 percent of surveyed schools were teaching future doctors about the ECS.
The hope is that this percentage has increased since 2013, but it’s believed that the increment is miniscule. This implies that the chances of one’s personal doctor knowing anything about the ECS—and how it can be positively influenced by cannabis—are very slim.
What’s also very important to understand is that by consuming cannabinoids from cannabis, which are health-beneficial by themselves, people can also increase the quantity of both cannabinoid receptors, and the internal endocannabinoids.
Small and carefully thought-out doses spur the body to produce more of its endogenous cannabinoids, like anandamide and 2-AG, and at the same time, increase the concentration of cannabinoid receptors CBI and CB2.
This is very valuable to people whose endocannabinoid system is not functioning properly, but more importantly, it demonstrates that cannabinoids from cannabis aren’t just a simple cure—they are also a tool that helps the body increase production of its own internal health regulators.
A greater number of receptors means that lesser quantities of cannabinoids are needed to produce a desired effect, and a carefully planned intake of cannabinoids also increases the amount of available endocannabinoids.
Check out the all-inclusive dosage guidebook—for which Greencamp collaborated with Dr. Dustin Sulak, who has extensive experience with treating patients with medical cannabis—to learn more about how to correctly and accurately dose cannabis.
What’s also very important to mention when consuming cannabinoid-based derivatives for medicinal purposes is that it is of utmost importance to consume products that aren’t isolated compounds, but, instead, have a full spectrum of cannabinoids in them, just like the real plant.
Besides THC and CBD, each strain of cannabis has a vast number of accompanying compounds that—even if found only in trace amounts—add to the synergistic effect of cannabis as a whole, in what’s dubbed the entourage effect.
Synthetic cannabinoids or isolated THC/CBD medications don’t have any minor cannabinoids or terpenes in them, and because of this they lack the cooperative effect leading to a much weaker therapeutic impact.
The state of the endocannabinoid system is very important as its purpose is to help regulate the proper functioning of all other physiological system of the body. The cellular receptors of the ECS can be positively influenced by cannabinoids from cannabis, causing incredibly diverse effects that are completely dependent on the medical issue in question, but the end goal is always the same: Homeostasis, a state of equilibrium of an entire organism.
Cannabis is such a powerful medicine for an incredibly large number of conditions because it directly influences an ancient and all-encompassing system in the body. Further educating oneself on this complex and fascinating topic can bring nothing but good.
The Endocannabinoid System and How THC Kills Cancer
There are over 20,000 studies on cannabinoids in the pubmed database, and few scientists who concentrate their work around cannabinoids can deny the tremendous therapeutic potential of cannabis. In fact, Dr. Christina Sanchez, a molecular biologist at Compultense University in Madrid Spain, has completed extensive research which led to one of the first discoveries that THC does indeed kill cancer cells.
The endocannabinoid system is a group of receptors in the brain that are involved in a variety of physiological processes including appetite, pain-sensation, mood, and memory. It mediates many physiological processes, including motor learning, synaptic plasticity, and appetite.
The Endocannabinoid System (ECS) maintains our biological systems by regulating each cell tissue. It uses Arachadonic acid/Omega 6 to make Endo-Cannabinoids: fatty molecules that communicate harm between cells. Dietary cannabis mimics the ECS by providing Cannabinoids when there is an Arachadonic acid deficiency or Clinical Cannabinoid Deficiency.
The discovery in the early 1990s of specific membrane receptors of marijuana’s psychoactive component 9-tetrahydrocannabinol (THC) opened the way to the revelation of a whole endogenous signaling system which is the endocannabinoid system.
One of the most incredible findings of the endocannabinoid system it that it appears to be conserved at least in all vertebrate phyla, and present in the structure of receptors and in their function, also in invertebrates, thus implying its participation in vital functions in almost all organisms.
Concentrate made from the flowering tops of the cannabis plant can produce a viscous oil containing large doses of active cannabinoids. The process was first made popular by Rick Simpson and commonly called RSO or Phoenix Tears. The ratio of compounds are typically 45%-65% THC and 7% to 12% CBD. Cannabidiol has been shown to reduce the intense “high” side effects of THC including the altered consciousnesses, confusion and anxiety.
Patients with several different forms of cancer have been able to use this oil topically and internally to force cancerous cells to kill themselves. RSO has often had a higher success rate than chemotherapy and radiation therapies. While these traditional therapies destroy cancer cells, they also destroy healthy tissue indiscriminately. RSO kills only cancer cells and leaves healthy tissue intact giving the patient better chances of recovery. RSO has also been therapeutic for treatment of chronic pain, inflammation, muscle spasms, intestinal disorders and more.
The Endocannabinoid System and How THC Cures Cancer
Recommended articles by Marco:
- 12 Facts About Microwave Ovens That Should Forever Terminate Their Use
- Cannabis-Based Batteries Could Change the Way We Store Energy Forever
- Cannabis Oil Cures Infant of Cancer, Dissolves Inoperable Tumor
- 5 Reasons to Juice Rather Than Smoke Cannabis
- Study Shows The Therapeutic Effects of Marijuana on Autistic Children
- 5 Diseases Proven To Respond Better To Cannabis Than Prescription Drugs
- Another Reason Marijuana is Illegal: It Prevents the Spread of HIV
- The U.S. Government Have Given One Man Over 130,000 Cannabis Cigarettes Since 1983 … for Bone Cancer!
- 4 Diseases That Can Be Reversed Naturally Without Pharmaceutical Drugs
- Woman Shrinks Inoperable Mass, Heals Her Thyroid Disease With Cannabis Oil
About the author:
Marco Torres is a research specialist, writer and consumer advocate for healthy lifestyles. He holds degrees in Public Health and Environmental Science and is a professional speaker on topics such as disease prevention, environmental toxins and health policy.
This article reproduced with permission from preventdisease.com
- Cannabis Articles / Medical Cannabis / Interesting Facts About Cannabis And The Endocannabinoid System
Interesting Facts About Cannabis And The Endocannabinoid System
Researchers are still trying to wrap their minds around the endocannabinoid system; how it functions and its role in our overall health. After all, it wasn’t until the 1990s that scientists inadvertently discovered the body’s CB1 receptors within the brain and central nervous system when attempting to determine what effects THC have on the human body. It’s becoming clear that the endocannabinoid system is responsible for balancing many of our body’s regulatory and immune system functions.
- Most medical professionals have little to no knowledge of the body’s ECS
In a 2013 survey, appropriately titled “Ignorance Is Not Bliss,” researchers found that only “13 percent of U.S. medical schools teach the endocannabinoid system to future doctors.”
Cannabis research is limited primarily due to its federally illegal status, which prevents government institutions like the FDA from conducting clinical studies. But medical marijuana research is expanding and more patients are demanding access, so there’s a good chance that teaching ECS curriculum to medical students may be mandatory in the upcoming years.
- The endocannabinoid system works in overdrive when diseases are present
Scientists have found that with a variety of illnesses, the ECS system shows increased activity and greater expression to restore the body’s natural balance.
- The ECS is the reason why cannabis relieves so many medical conditions
Ingesting cannabinoids signals the body to create more endocannabinoids and build more receptors. Triggering this system naturally limits inflammation and repairs cells, among many other therapeutic benefits. The previously mentioned, “Ignorance Is Not Bliss” study reads,
The discovery of the ECS will replace the current medical system of managing and treating disease. Instead of management of symptoms after disease has occurred, we will prevent disease and cancer by manipulation of the CES.
- There are more endocannabinoid receptors outnumber other neurotransmitter receptors in the brain
Anandamide, the first endocannabinoid ever discovered is abundant in the brain. Called the “bliss molecule” it plays an important role in memory, critical thinking, motivation and appetite.
- You don’t need psychoactive THC to stimulate the endocannabinoid system
CBD found in industrial hemp is among many cannabinoids which activate the ECS to provide a range of physical and psychological health benefits. However, THC and CBD combined pack a powerful punch by bringing out the other’s best traits.
- An endocannabinoid deficiency is linked to a number of common illnesses
A weakened ECS appears to be related to hypersensitivity regarding chronic pain and inflammatory conditions. The National Institutes of Health has even named the theory, Clinical Endocannabinoid Deficiency and is examining the,
prospect that it could underlie the pathophysiology of migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions alleviated by clinical cannabis.
- All vertebrate groups have an ECS system
It has been discovered that fish, reptiles, amphibians, birds, mammals and even a few non-vertebrates have this incredible regulatory structure. It is shown to be involved in reproduction, cell progression and a variety of physiological functions.
The International Journal of Neuropsychopharmacology
The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system
Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression.
However, the mechanistic bases of CBD action are unclear.
Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS).
Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. …
CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze.
This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1–selective antagonist AM251 prevented CBD actions.
Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. …
These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.
PLOS ONE (Public Library of Science)
Activation of Type 1 Cannabinoid Receptor (CB1R) Promotes Neurogenesis in Murine Subventricular Zone Cell Cultures
The endocannabinoid system has been implicated in the modulation of adult neurogenesis.
Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures.
Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes.
Stimulation of the CB1R … increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres … Moreover, … treatment for 48 h, increased proliferation …
Surprisingly, stimulation of CB1R … also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures.
Moreover, by … a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells.
This proneurogenic effect was blocked when SVZ cells were co-incubated with … the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation.
In accordance with an effect on neuronal differentiation and maturation … also increased neurite growth …
Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.
The Journal of Clinical Investigation
Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects
The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis.
Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown.
This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change.
We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis.
This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors …
Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects.
… suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.
Cannabis (marijuana, hashish, or cannabinoids) has been used for medical and recreational purposes for many centuries and is likely the only medicine or illicit drug that has constantly evoked tremendous interest or controversy within both the public domain and medical research.
Cannabinoids appear to be able to modulate pain, nausea, vomiting, epilepsy, ischemic stroke, cerebral trauma, multiple sclerosis, tumors, and other disorders in humans and/or animals.
However, marijuana has been the most commonly used illicit drug in developed countries, producing acute memory impairment and dependence/withdrawal symptoms in chronic users and animal models.
Cannabis acts on 2 types of cannabinoid receptors, the CB1 and CB2 receptors, which are distributed mainly in the brain and immune system, respectively.
In the brain, CB1 receptors are also targeted by endogenous cannabinoids (i.e., endocannabinoids) such as anandamide (AEA), 2-arachidonylglycerol, and arachidonylethanolamide.
The recent discovery that the hippocampus is able to generate new neurons (i.e., neurogenesis) throughout the lifespan of mammals, including humans, has changed the way we think about the mechanisms of psychiatric disorders and drug addiction.
The sub granular zone of the dentate gyrus (SGZ) in the adult brain contains neural stem/progenitor cells (NS/PCs) capable of producing thousands of new granule cells per day.
We, and others, have shown that these newborn hippocampal neurons are functionally integrated into the existing neuroanatomical circuitry and are positively correlated with hippocampus-dependent learning and memory processes and the developmental mechanisms of stress and mood disorders. …
Chronic administration of the major drugs of abuse including opiates, alcohol, nicotine, and cocaine has been reported to suppress hippocampal neurogenesis in adult rats, suggesting a potential role of hippocampal neurogenesis in the initiation, maintenance, and treatment of drug addiction.
The recent finding of prominently decreased hippocampal neurogenesis in CB1-knockout mice suggests that CB1 receptor activation by endogenous, plant-derived, or synthetic cannabinoids may promote hippocampal neurogenesis.
However, endogenous cannabinoids have been reported to inhibit adult hippocampal neurogenesis.
Nevertheless, it is possible that exo- and endocannabinoids could differentially regulate hippocampal neurogenesis, as exo- and endocannabinoids act as full or partial agonists on CB1 receptors, respectively.
The goal of the present study was to test the hypothesis that the potent synthetic cannabinoid HU210 is able to promote hippocampal neurogenesis, leading to the anxiolytic and antidepressant effects of cannabinoids.
We demonstrate here that both HU210 and the endocannabinoid AEA promote proliferation of embryonic hippocampal NS/PCs without significant effects on their differentiation, resulting in more newborn neurons.
The effects of HU210 on adult hippocampal neurogenesis were quantified in freely moving rats and were correlated with behavioral testing.
We show that 1 month after chronic HU210 treatment, rats display increased newborn neurons in the hippocampal dentate gyrus and significantly reduced measures of anxiety- and depression-like behavior.
Thus, cannabinoids appear to be the only illicit drug whose capacity to produce increased hippocampal newborn neurons is positively correlated with its anxiolytic- and antidepressant-like effects.
Tune in this Sunday!
The G2Voice Broadcast # 146 –
What is the Endocannabinoid System in the body?
Sunday, June 30th, 2019
10 AM CST
Let’s change the world together!
Bishop Mark S. Grenon
Co-founder of the Genesis II Church of Health and Healing
- Mark Grenon