Cannabis, which has more than 25 thousand uses today, is known as one of the oldest plants used as a raw material. Among the areas where cannabis is most commonly used are food, beverage, cosmetics, personal care, food supplement, medicine, fabric, paper, and building materials. Cannabis is also used widely for recreational purposes. So do you know how cannabis works in the human body?
Cannabis has at least 60 chemical compounds known as cannabinoids that act on receptors in our brain. Cannabinoids help keep neurons in our brain functioning and expand our thoughts. Like alcohol, caffeine, and sugar, cannabinoids also create a dopamine effect in our brain. This creates a feeling of relaxation and happiness. THC, which is among these chemical components, is among the substances that provide the most well-known feature of cannabis, such as drunkenness that makes people happy.
The endocannabinoid system (ECS) is one of the most critical physiological systems required to strengthen human health. It is a complex and common neuromodulatory system discovered in the 1990s by researchers working on a cannabinoid known as THC. Although research continues to find out more about ECS, it has been discovered that it plays an important role in the central nervous system.
In addition to memory, it regulates various bodily processes and functions such as mood, sleep, appetite, fertility, and reproduction. This system consists of endocannabinoid recycling, endocannabinoids, and cannabinoid receptors. CB1 receptors, peroxisome proliferator active receptors (PPAR), and transient receptor potential (TRP) channels, which come from the largest structure except for CB2, are used by some cannabinoids.
The function of the endocannabinoid system is to modulate the central nervous system and at the same time maintain homeostasis. Homeostasis of all organs in the body is defined as a state of equilibrium in which it functions at optimal levels for cognitive, emotional, and psychological balance.
Endocannabinoid System Explains How Cannabis Works
Cannabis is a plant called Cannabis Sativa and has been cultivated in many parts of the world for 4500 years. This plant is grown for its oil and fiber and is also used as an addictive reliever such as marijuana and poppy. The active ingredient in cannabis is delta-9 tetrahydrocannabinol (THC), an alkaloid. The plant also contains more than 60 cannabinoids. Some of these changes the effectiveness of THC. Artificially derived THC (dronabinol) is used for the treatment of nausea-vomiting resulting from chemotherapy and anorexia associated with immune deficiency, virus infection. It has been used as a weight enhancer in cachexia.
The endocannabinoid system contributes to the physiological regulation of energy balance, food intake, glucose, and lipid metabolism at the center and periphery. Cannabinoids achieve this effect by interacting with two types of receptors called cannabinoid-1 (CB-1) and cannabinoid-2 (CB-2). CB-1 is primarily found in different parts of the brain, secondary adipose tissue, myocardium, vascular endothelium, and sympathetic nerve endings. CB-2 is located in primary lymphoid tissue and peripheral macrophages. Both receptors act as transmembrane G-proteins. Although a third CB-3 receptor has been proposed, it is not yet well understood.
Cannabinoid receptors have a tendency to at least two endogenous ligands. These are the small lipid molecules arachidonic ethanolamide (anandamide) and 2-arachidonic glycerol (2-AG). Under normal conditions, the endocannabinoid system is not active. It can be activated quickly locally on demand. Endocannabinoids can be isolated from membrane phospholipids (anandamide-AEA) or triglycerides (2-arachidonylglycerol-2-AG). Its effectiveness is lost when it is broken down in the cell by the effect of the fatty acid amide hydrolase enzyme (FAAH).
In genetic animal models of obesity, the brain endocannabinoid level CB-1 is down-regulated. Experimental animals with insufficient CB-1 genes are thin and resistant to diet-induced obesity. Similarly, when the CB-1 blocking agent was administered to experimental animals, food intake and body weight decreased. In the study of its mechanism, CB-1 activation in experimental animal adipose isolates increased the lipogenic enzyme lipoprotein lipase activity.
In addition, blocking of CB-1 increased adiponectin gene expression in adipose tissue. Stimulation of CB-1 receptors in fat cells in obese animals increases lipogenesis and decreases adiponectin production. The endocannabinoid system is overactive in genetically obese animals, and these animals are extremely eager for food intake. With these effects, the endocannabinoid system contributes to the physiological regulation of energy balance, food intake, glucose, and lipid metabolism in the central nervous system and periphery.
Cannabinoid administration in humans affects the blood pressure of the system together with vasodilation and tachycardia. Endocannabinoids achieve their vasodilation effect by activating the CB-1 receptor on smooth muscles in the brain. These compounds also show vasodilation effect by increasing nitric oxide synthesis in the endothelium. It has been suggested that some of the vasodilation effects may be independent of the CB-1 receptor system.
It has been reported that the endocannabinoid system may be involved in the regulation of vascular tone in liver disease, hypertension, and other disorders. In advanced cirrhosis, endocannabinoids initiate a vasodilator state as a result of interaction with the CB-1 receptor. In hypertensive animals, the cardiac and vascular endothelial CB-1 system is active and these animals show a vasodepressor / hypotensive response to anandamide compared to normal. It has been observed that when the CB-1 receptor is inhibited, the anandamide is abolished in hypertensive animals. The absence of such a situation in normal animals indicates that the CB-1 system is not active under normal conditions.
How Exactly Endocannabinoid System Works in the Human Body?
The endocannabinoid system is one of the notable biological systems in the body. The existence of this system was discovered in the 1990s when researchers researching the main psychoactive cannabinoid (THC) of cannabis. Since then, ongoing work has been done to clarify the functioning and biological basis of the system. Understanding the regulatory endocannabinoid system in response to cannabinoids is important due to the increased legalization of cannabis.
Despite the effects of cannabinoids in humans, research offers new ideas, although more effective treatments for cannabis and cannabinoid products have not been developed. Currently, research focuses on understanding how the endocannabinoid system can be used to treat illnesses and illnesses is being conducted. The following paragraphs contain more information about the endocannabinoid system.
The word endocannabinoid stands for cannabinoid gain from cannabis and endo is an acronym for the word endogenous. This means that it is produced naturally in the body. In other words, endocannabinoid means cannabis pseudo-substances that naturally occur in the body. ECS itself consists of three parts and these are as follows:
- Receptors in the nervous system and around the body where endocannabinoids and cannabinoids bind to each other
- Enzymes that help break down endocannabinoids and cannabinoids
ECS is not just a natural part of the body, however, it is very important. There are many claims on the medicinal properties of marijuana in general or the cannabinoids THC and CBD. With so many apparently indifferent effects, many people who want the drug to be legalized might wonder if it is a scam. However, science supports almost all of these claims and states that the wide-ranging effects are due to the extent and size of the endocannabinoid system.
Known Facts About the Endocannabinoid System
The functions that are responsible for the endocannabinoid system are known in the literature. These functions are the effect of appetite, cardiovascular system function, chronic pain, immune system responses, memory, metabolism, mood, motor control, pleasure-reward reproduction, skin and nerve function, tension and fertility, and sleep. However, this list can be expanded in more detail. The system is brought into action by introducing cannabinoids into the body and is continuously active due to its role in maintaining homeostasis, especially in the regulation of leptin-related appetite.
The three main components together form the endocannabinoid system, these components are endocannabinoid receptors in the system, enzymes that catalyze the breakdown of endocannabinoids and cannabinoids. Cannabinoids interact medially with the endocannabinoid system. Studies have shown that THC, the main psychoactive cannabinoid in cannabis, mimics the effects of endocannabinoids by interacting and binding with endocannabinoid receptors.
THC can interact with two human cannabinoid receptors located in the human endocannabinoid. THC also interacts with CB1 receptors found in the central nervous system as well as CB2 receptors on specialized cells in the peripheral system, digestive system, and immune system. THC is able to activate both of these receptors, which leads to the effect of the entire range of processes involving these receptors, affecting the body as well as the mind.
In some cases, THC can create pleasurable effects due to its effect on these receptors, such as a decrease in pain. In some cases, it can trigger feelings of anxiety and paranoia. There are currently ongoing studies investigating how synthetic THC cannabinoids can be produced and activate these receptors in, particularly beneficial ways. Cannabidiol (CBD) is the other essential cannabinoid found in cannabis. The effects of CBD on the body are different from THC as CBD is not psychoactive. It is generally believed that, unlike THC, CBD generally does not have negative effects.
Immediately, scientists are aware that CBD does not activate the CB1 and CB2 receptors the way THC does, but the underlying mechanisms remain unclear. studies to investigate the effects of CBD are ongoing. Currently, it is the theory that CBD prevents the breakdown of endocannabinoids and causes cannabinoids to remain active in the system longer and have reproductive effects on the body. Another possibility is the presence of an undiscovered receptor in the endocannabinoid system. Although certain mechanisms are being investigated immediately, CBD has been found to reduce anxiety and nausea.
Endocannabinoid System as a Therapeutic Target
There is an increase in research focusing on the use of the endocannabinoid system as a therapeutic purpose. Sativex, a cannabinoid derived from the cannabis plant, is approved in Canada for pain and spasticity in multiple sclerosis patients. Current research has focused on the development of drugs that act as CB. Receptor antagonists (inhibitors) may have obesity remedial potential after quitting smoking. Therapeutic applications for CB receptors are aimed at treating neurodegenerative diseases such as Alzheimer’s, Parkinson’s diseases, and immunoregulation.
Basically, homeostasis is the body’s effort to keep everything in the right place, and it tries to keep the internal environment stable and optimal, no matter what happens in the environment. Considering all the indicators on the dashboard of a car or aircraft, they all inform the operator whether the objects are working in the on-site area. Just like electronic devices in a car or airplane, the body works non-stop to monitor significant levels and functions in itself.
The Endocannabinoid system is constantly active to monitor signs of appetite, such as low or high, fever, whether hormone levels are as they should be, and whether the heartbeat is healthy. When something is out of the normal range, the body activates the ECS to help correct it. In other words, when it is really hot and sweating is started, ECS works to cool the body. Stomach rumbling is ECS that reminds us to eat because there is a need to eat something. ECS does this through cannabinoid receptors located in specified tissues. There are at least two generations of cannabinoid receptors and they are as follows:
CB1 (nerves of the brain and spinal cord) located in the central nervous system
CB2, which is located in the peripheral nervous system (nerves in your extremities), digestive system, and special cells in the immune system
Cannabinoid receptors are believed to be among the most abundant in the central nervous system, and some researchers hypothesize that a third undiscovered one could also be possessed. Through these receptors, ECS has been instrumental in regulating many notable functions, and these are:
- Immune function
- Inflammation, including neuroinflammation
- Reproduction and fertility
- Engine control
- Temperature regulation
- Passion and reward
The body sensitively activates the ECS, thus affecting only what it needs. For example, if reproductive hormones are insufficient, they try to regulate them without altering their digestion or immune system. It’s different than what happens if someone smokes marijuana and fills their system with cannabinoids. The drug then has far-reaching effects on physiology, some of which may be beneficial while others may be harmful. Homeostasis is essential for well-being and survival, so ECS can cause most problems when the drug isn’t working.
As cannabis products can trigger the activity of ECS, they are clear targets for potential treatments, and a ton of research is being done worldwide. There are also drugs produced from synthetic (laboratory-created) cannabinoids. There is a lot of positive research on cannabinoid-based therapies, and changes in legal status are being directed as the substances and this system are better understood.
When someone smokes marijuana, a cannabinoid from the plant binds to the CB1 receptor in the brain and produces a high. This cannabinoid is called THC, which is short for delta-9-tetrahydrocannabinol. One of your own endocannabinoids that bind to the same receptor is called anandamide. Even though the THC and anandamide seem like same, anandamide does not cause a high feeling. Anandamide has a soothing effect though, it is named after ananda, which means joy in Sanskrit.
The reason anandamide does not cause high and THC do lie in something called the FAAH enzyme. FAAH’s job is to break down anandamide and other endocannabinoids. It works fast on what the body creates, whereas it cannot break down THC. This means that THC remains much longer and thus has a much greater effect. In the brain, cannabinoids, and endocannabinoids work as neurotransmitters (chemical messengers that transmit information from one cell to another).
Neurotransmitters all interact with many separate receptors and thus have many different effects. CDC, a plant-based cannabinoid, and cannabidiol are of as much interest as THC. It does not have any psychoactive properties, so its benefits come without the high feeling that THC causes. A familiar function of CBD in the brain is to prevent the FAAH enzyme from breaking down anandamide, so anandamide can be more effective. Therefore, it is believed that CBD can help treat anxiety disorders.
Cannabis Working Principles: Cannabinoids
A cannabinoid is a naturally occurring compound found in various plants, including Cannabis sativa. Although we usually know about cannabis plants and cannabinoids, we can show you 8 examples of herbs that are not cannabis but contain medicinal cannabinoids. There are three types of cannabinoids as phytocannabinoids, synthetic cannabinoids, and endocannabinoids. In the following paragraphs, I will talk about the endocannabinoid produced in the human and animal body in order to show how they work in the human body.
Endo means endogenous, indicating that it originates from the body, while cannabinoid refers to the group of compounds that activate this system. The endocannabinoid system, which plays an important role in the human body, is a receptor system involved in various physiological processes in the brain, including appetite, pain-sensation, mood, and memory. It regulates and protects every cell tissue of our biological system. It interacts with cannabinoid receptors to regulate these essential functions.
The endocannabinoid contains two receptors, cannabinoid 1 (CB1) and cannabinoid 2 (CB2). CB1 receptors are found throughout the body but mostly in the brain and spinal cord. CB2 receptors are found in the peripheral nervous system. They are especially concentrated in immune cells. 2-AG (2-arachidonoyl glycerol) and anandamide are the largest known endocannabinoids. While 2-AG is found in higher concentrations in the brain, anandamide is found in higher concentrations in other parts of the body.
Both can bind to CB1 and CB2 receptors, but how long their binding and activation activity will last for each receptor is different. Endocannabinoids are neurotransmitters; They are produced when the body indicates that it needs it, and they are temporary. Once released, it is broken down by enzymes containing FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase).
THC Activates CB1 and CB2 Receptors
Exogenous vehicles that arise outside the body are considered exogenous while cannabinoids such as tetrahydrocannabinol (TCH) and cannabidiol (CBD) found in cannabis. Regarding the cannabinoids found in cannabis, the researchers found that THC binds to both CB1 and CB2 receptors and activates them like an endocannabinoid. CBD does not bind directly to cannabinoid receptors. CBD is responsible for breaking down anandamide, the body’s most important endocannabinoid.
It works by inhibiting an enzyme called FAAH. When FAAH is inhibited, it cannot break down anandamide normally. This causes anandamide to accumulate in the brain, allowing us to use it more effectively. It also plays an important role in the maintenance and regulation of endocannabinoid system homeostasis. The endocannabinoid system is thought to treat many ailments. Medical cannabis is also the most common way to target the endocannabinoid system to treat diseases like these.
It is known to produce therapeutic effects by interacting with the endocannabinoid system, including THC and CBD. It can be prescribed for many ailments such as nausea, multiple sclerosis, and epilepsy in Europe and America. Those who are disturbed by the psychological effects of cannabis may prefer those that contain only CBD.
However, Dr. Christina Sanchez, a biologist at Complutense University in Madrid, examines the anti-tumor and other properties of medical cannabis, particularly the therapeutic benefits of cancer and cannabinoids. One of the known names in this subject. She completed one of the first comprehensive studies that THC actually kills cancer cells. According to the findings, the endocannabinoid system appears to be preserved in all vertebrate phyla. It is also present in the structure and functions of invertebrates, receptors. This implies its participation in vital functions in almost all organisms.
A concentrate made from the flowering parts of the cannabis plant can produce an oil that contains large doses of active cannabinoids. This process was first popularized by Rick Simpson and is often called the RSO or Phoenix Tears. The proportion of compounds typically contains 45-60 percent THC and 7-12 percent CBD. It has been shown that cannabinoid reduces intense “high” side effects of THC, including complex and anxiety states.
Patients with different types of cancer can use this oil to force cancer cells to die locally and internally. Reportedly, RSO generally has a high success rate in chemotherapy and radiation treatments. While these traditional treatments destroy cancer cells, they also indiscriminately destroy healthy tissues. RSO only kills cancer cells and leaves healthy tissue intact giving the patient a better chance of recovery. RSO has also been useful for treating chronic pain, inflammation, muscle spasms, bowel disorders, and more.
How Synthetic Cannabinoids Work?
Synthetic cannabinoids are, as the name suggests, synthesized or produced in the laboratory. They are not organic cannabinoids derived from hemp. When it comes to synthetic cannabinoids, we have to wrap the film from the very beginning until the invention of Tetrahydracannabidinol (THC).
Nearly 50 years ago, Raphael Mechoulam, who lives in Israel, found that the substance Delta-9-tetrahydrocannabinol (9-THC) was responsible for the main psychoactive properties of cannabis, namely its “head-boggling” properties.
In those years, cannabis was not legal, and it was not uncommon to research such substances. During the investigation, Mechoulam’s path crossed with the police many times for these reasons. In this way initiated by Mechoulam, cannabis research has gained great momentum over time, with many scientists showing the functioning of THC on the brain and body.
The discovery of synthetic cannabinoids, just like Ecstasy and LSD and many recreational substances, is owed to academic research. John W. Huffman’s main goal, which played an important role in the discovery and development of synthetic cannabinoids, was to find a substance in the brain that would regulate symptoms such as “appetite, nausea, mood, pain, and inflammation.” In 1993, Huffman synthesized this substance, which he named JWH-018, and published a series of academic studies describing the formula.
When asked what he thought of with synthetic cannabinoids, Huffman, who is now in his 80s, gave the following answer: “When I heard that the substance I found was used for an enjoyable purpose, I found it funny. But when I heard about the bad effects of the substance, I thought I thought someone opened Pandora’s box ”.
The first thing we need to understand about synthetic cannabinoids is that synthetic cannabinoids do not consist of just one substance. Synthetic cannabinoid is a collection of many different substances under one category. Synthetic cannabinoids are like a family of man-made chemicals. Although the fact that cannabis is illegal cannot stop scientists, as a result of long efforts, these scientists come up with a substance that functions like THC in the brain and resembles THC in chemical properties.
In theory, it is possible to use this substance in many different ways, but manufacturers have tried to make their products similar to traditional cannabis consumption by spraying the synthetic cannabinoid onto dried plant parts to resemble organic cannabis. Although there are many different ways to consume synthetic cannabinoids, as a marketing technique, products are often designed to be consumed with a pipe or hookah or wrapped in cigarette paper.
At the end of the day, it has become difficult to predict what is in these substances sold as traditional hemp, and the similarity between cannabis and synthetic cannabinoid has come to an end from this point on. Healthcare professionals are unhappy with the term “synthetic cannabis” because they think it aims to simulate the synthetic substance to the organic one. What exactly synthetic cannabinoids do today comes from user reviews on the internet and from hospital reports uncovered.
Users according to the comments found on the Internet transient psychosis, hallucinations, vomiting, high blood sugar, headache, extreme anxiety, panic attack, and hypertension. Emergency reports, on the other hand, talk about headaches, hallucinations, and heart palpitations. Usually, these symptoms disappear after 1-2 hours. Although the effect of synthetic cannabinoids may sound similar to normal cannabis, cannabis users say that the effect of synthetic cannabinoids is much more severe and uncontrollable.
Although it sounds like there is a similarity between the two substances, there has not been any study on synthetic cannabis on humans before. Chemical analyzes of JWH-018 and THC on mice show that a 50mg synthetic cannabinoid has a similar effect to 200mg of cannabis (14.8mg THC) in the brain.
The description of this synthetic substance, which was used for various scientific researches until 2002, suddenly passed into the hands of street chemists. In 2004, the first synthetic cannabinoid is launched on the market. The best known of the first synthetic cannabinoids are “K2” and “Spice”, these substances are sold as legal cannabis alternatives in certain places. The name of the active chemical in these substances is JWH-018.
According to the statement of the United Nations Office on Drugs and Crime, by 2008 and 2009, substances using Huffman’s formula were more popular than ever in Europe and the USA. Behind this popularity quickly, if not fully, JWH-018 is banned, but the substance called JWH-073 is launched on the market. This substance is the ancestor of the Bonzai substance that everyone has heard of today. This time, even if it says “not for human consumption” on the packages, these items have gained popularity in certain countries.
The first case of death from the use of JW-073 occurred in 2010. However, street chemists do not slow down, this time they launch substances such as JWH-081, JWH-122, JWH-210 under different attractive names (Boom, cyclone, Jamaican gold, pandora’s box, etc.) and synthetic cannabinoids reach popularity like never before. Gas stations, internet shops, small markets, tobacco vendors, and similar places start selling this item. The use of this substance in Cyprus, Greece, and similar countries even surpasses normal cannabis.
This is because synthetic cannabinoid is a more accessible substance, so it has been seen as safer. Because its constantly changing formula has made it difficult to detect this substance in standard drug tests. Difficult detection in drug tests has made the synthetic cannabinoid more attractive to young people, soldiers, and people undergoing drug testing.
While it is still a matter of debate whether synthetic cannabinoids are a deadly substance, one thing is certain. Synthetic cannabinoids are a more dangerous substance than organic cannabis, and the constant modification and introduction of this substance on the market increase the risk of being inspected. The biggest reason for the emergence of synthetic cannabinoids is that organic cannabis is prohibited and seen as a more dangerous substance by law.
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