Are you familiar with the endocannabinoid system? Amazingly, it's essential for almost every aspect of our daily lives. The endocannabinoid system is a communication system that helps regulate different processes in our body.
While most people are familiar with the sympathetic nervous system's fight-or-flight response, the endocannabinoid system (ECS) is a relatively recent discovery critical to our overall health and well-being.
With the renewed interest in cannabis and CBD, the ECS system is at the forefront of international research and drug development. So it's exciting to think about the possibilities that could come from further studying and understanding this incredible system within our bodies.
We spoke with Dr. Babak Larian to learn more about the ECS system, its functions, and how it interacts with cannabis – it's a journey of discovery.
Let's get going.
What Is the Endocannabinoid System?
The endocannabinoid system is believed to have evolved over millions of years, and it's present in all types of animals, from humans to insects. Its main job is to ensure that our bodies work correctly and that everything is harmonious.
Dr. Larian explains, “The endocannabinoid system is involved with bringing your body back into balance.” He describes the ECS system as like a limiter for a car engine revving too high, which may help restrict and bring it back down to an average level to function efficiently. The ECS system does the same for our nerves, helping regulate their activity and keep everything running smoothly.
So, when something is out of balance, like if we're in pain, have inflammation, or struggle with seizures, this master regulator in our bodies helps keep everything balanced.
What Is the Endocannabinoid System Made Of?
The ECS system is made up of three main parts:
The discovery of the ECS system is relatively recent, dating back to the early 1990s when researchers studying the effects of THC, a compound found in cannabis, stumbled upon it.
Experts are still working to understand the ECS system better, but we know it plays a crucial role in various bodily functions, such as sleep, mood, appetite, memory, and reproduction.
Endocannabinoids are natural chemicals our bodies make, similar to those found in cannabis plants. Our body produces endocannabinoids when required rather than in advance. The nervous system uses these chemicals to communicate with different body parts.
Your body can produce these chemicals because they come from fats – everyone has an active ECS system. Dr. Larian outlines the role of an endocannabinoid in regulating nervous impulses:
“When these nerves feel that the previous nerve is firing too hard… the extra input sends an endocannabinoid. This extra chemical… …goes backward and tells the nerve, ‘Calm down. You’re working too hard. Go back to your baseline and restart.’”
Scientists have extensively researched two significant types of endocannabinoids:
- The messenger or "bliss" molecule: Arachidonoyl ethanolamide (anandamide or AEA)
- 2-AG: 2-arachidonoyl glycerol enhances the function of CB1 receptors and is the primary natural molecule that can bind to CB2 receptors.
Endocannabinoids in our body interact with specific parts of our cells called endocannabinoid receptors. These receptors are found on different types of cells in our body and can cause different reactions when activated.
Scientists have studied two of these receptors of importance for the effects of endocannabinoids.
- Cannabinoid 1 (CB1) Receptors: They are primarily found in the central nervous system, especially in neurons or nerve cells in the brain. THC and anandamide also bind with these receptors.
- Cannabinoid 2 (CB2) Receptors: Found in the peripheral nervous system and immune cells. They are like tiny keyholes unlocked by molecules called 2-AG. The CB2 receptors can help reduce inflammation and other immune responses.
Enzymes are natural substances our bodies produce to create and break down certain chemicals. For example, when a cell needs to send a message, endocannabinoids are made by breaking down fats with the help of enzymes.
After the endocannabinoids do their job, they are removed from the cells by a particular protein and broken down further by other enzymes. Regarding endocannabinoids, two types of enzymes help break them down so they don't stay in our body for too long:
- Fatty acid amide hydrolase (FAAH): findings suggest that FAAH has a natural ability to break down anandamide and 2-AG.
- Monoacylglycerol acid lipase (MAG-L): Once the 2-AG molecule has completed its function, it is taken back into the cells and broken down by an enzyme called MAGL. The body uses the broken-down product to produce other compounds.
Understanding how these enzymes work could help create new treatments for diseases like addiction.
What Does the Endocannabinoid System Do?
Studies have shown that CB1 receptors, found in the presynaptic region of neurons, can block the transmission of signals. Meanwhile, enzymes that produce endocannabinoids are located in a different place called the postsynaptic area and are activated when there is an increase in calcium ions or stimulation of specific receptors.
It leads to the production of endocannabinoids, which act as retrograde messengers, i.e., they move backward from the postsynaptic region to the presynaptic area. This process helps regulate the communication between neurons; much experimental evidence supports it.
Researchers have identified three intricate processes essential in balancing neuron excitation and inhibition. And when something disrupts the ECS, it can lead to disease, mental health problems and may cause psychiatric disorders such as schizophrenia.
Initially, people believed the ECS system only affected the brain and nerves, but researchers have since discovered that it affects almost every body part. It includes the skin, bones, muscles, heart, and digestive system. Endocannabinoids also regulate the release of neurotransmitters such as dopamine and serotonin, affecting memory, mood, and pain response.
The ECS can play a double-edged sword in regulating appetite. It was effective in a mouse study where blocking endocannabinoid receptors led to starvation. But Rimonabant drug trials on humans were approved in 2006 to treat obesity by blocking CB1 receptors. However, it was removed from the market in 2008 due to severe mental health issues in some people who took it.
Dr. Larian highlights the distinction between chemical treatments and natural solutions that support the ECS as “poisoning you versus harnessing your defenses.” He speaks of his astonishment at discovering how complex this organic system was compared with the blunt instruments of drug-based treatments:
“On a micro level, each system has other ways of balancing. Getting to that understanding was a paradigm shift. It made me think about addressing illnesses more than just – I’m treating this particular illness, to how can I get your body to a point where your body’s capacities and abilities can take care of the problem. Which is probably better than I can.”
The ECS is involved in many physiological reactions and disease states, stressing the need for scientists to explore how the ECS interacts with many different parts of our body, including our nervous system, immune system, organs, and more. It's a highly complex system, indeed.
Natural Cannabinoids & the ECS System
The discovery and research on the ECS system have opened up possibilities for using natural cannabinoids like THC and CBD for medical purposes.
Some approved external compounds can activate CB(1) and CB(2) receptors in human tissue to help reduce the symptoms or underlying causes of disorders requiring adequate treatment.
While further research is required to understand how natural cannabinoids interplay with the ECS, there is growing excitement over their potential as a supplement.
Insights From ECS Research: Potential Benefits of Cannabinoids
The U.S. National Academy of Sciences, Engineering, and Medicine conducted a study in 2017 which found that cannabinoids can help treat various conditions.
- Cannabinoids effectively reduce chronic pain symptoms in adults. People who were treated with cannabis or cannabinoids had a significant reduction in pain symptoms.
- There is moderate evidence that cannabinoids effectively improve sleep in people with chronic pain, obstructive sleep apnea, and fibromyalgia.
Sleep disorders can be divided into different categories, such as insomnia, sleep-related breathing disorders, and circadian rhythm sleep-wake disorders. Millions of adults in the U.S. have some form of sleep disorder, and evidence suggests that the ECS system might play a role.
Low doses of cannabis may help people fall asleep faster, while higher doses may cause them to take longer to fall asleep. Therefore, cannabinoids could potentially be used to treat sleep disorders. Additionally, THC may affect the deep sleep stage, which is crucial for memory and learning.
There is limited but promising evidence that cannabinoids could treat post-traumatic stress disorder (PTSD), Tourette's syndrome, and traumatic brain injury.
How Does the Endocannabinoid System Interact With CBD and THC?
Compared to CBD, THC has a strong bond with CB1 and CB2 receptors. THC is also potent in reducing inflammation, with 20 times the strength of aspirin and twice that of hydrocortisone steroids.
Moreover, THC interacts with several other receptors and enzymes in the body. According to studies, it can assist in lowering risks associated with organ transplant surgery. Other studies show using cannabis may ease opioid withdrawal in people.
CBD doesn't attach itself firmly to the CB1 and CB2 receptors but indirectly affects the ECS. For example, CBD can prevent enzymes from breaking down anandamide, which makes you feel good.
FAAH is a protein that helps break down lipids—fatty acids or their derivatives—in our bodies. It has a unique part called the "membrane access channel," allowing the lipids to get to the area of the protein that breaks them down. This channel consists of specific types of molecules.
A study used computer simulations to see how well CBD interacts with FAAH, an enzyme in our body. They found that CBD can fit into a small space inside the FAAH enzyme and get close to a specific part, suggesting CBD may block the enzyme's activity, similar to other substances that can do this.
When they compared CBD to the AEA compound, they found they both fit in the same spot in the enzyme, which adds to the evidence that CBD could be a competitor for inhibiting FAAH.
What Is the Role of Minor Cannabinoids?
When we talk about minor cannabinoids, we refer to the other lesser-known chemical compounds from the cannabis plant. These phytocannabinoids affect our bodies because they can also bind to multiple types of receptors, making them ideal for treating various medical conditions.
Some of these compounds, like CBN and THCV, can bind to the same receptors as the more famous compound in cannabis, THC. However, they are not as potent as THC when binding to those receptors.
These compounds have different properties and effects, but none of these minor cannabinoids have shown any psychoactive effects. Nevertheless, scientists continue studying these minor cannabinoids to understand their functioning and potential medical uses.
Some compounds offer potential therapeutic benefits, while researchers are still studying others.
Are There Ways To Enhance the ECS?
Until recently, many believed only cannabis had substances that affected the ECS system. However, in recent decades, scientists have found that components in other plants can also interact with this system.
Dr. Larian stresses how plant-based remedies have been an integral part of regulating the body throughout all stages of evolution. Animals understand which plants to seek out to help them with indigestion, aches, pains, and numerous other issues.
The key, Dr. Larian suggests, is that the body must maintain balance – and endocannabinoids play an essential role in maintaining balance. “You can’t have a network or system that harmonizes so well without the ability to bring itself back to balance.”
And plants have so many of the answers.
Some of these plants are common in our diets and include herbs, spices, chocolate, exotic kava, black pepper, and more. Their components can make the system more active, some can make it less active, and others can change different aspects of it.
Some essential oils contain beta-caryophyllene (BCP), common in black pepper, oregano, lemon balm, cloves, and hops. BCP is known for its ability to naturally help with inflammation and pain relief due to its ability to stimulate the CB2 receptors.
Science Behind Nature
Researchers have suggested the plant compound (E)-BCP interacts with the same site as THC. Molecular modeling studies indicate the activation of a specific receptor by (E)-BCP triggers a complete program involving inhibition. Like other CB2 receptor-selective medication, (E)-BCP may provide anti-inflammatory effects.
Recent studies have found that black truffles grown under specific conditions contain significant levels of AEA, which can activate the CB1 and CB2 receptors. Besides this, there are other cannabinoids found in nature, known as endo/phytocannabinoids, including N-lin oleoyl ethanolamide (LEA) and N-oleoyl ethanolamine (OEA), which are both present in cocoa.
Eating truffles and chocolate could be good for more than just satisfying our taste buds! And consuming certain plants and vegetables that contain prebiotic dietary fiber helps promote good gut bacteria growth. Recent studies have shown that the microbiota, the microorganisms in our gut, can affect the system's activity.
Timeline of Discoveries Leading to Our Understanding of the Endocannabinoid System
Researchers have found more than 100 cannabinoids in cannabis plants. However, the two most important are cannabidiol (CBD) and tetrahydrocannabinol (THC). CBD was first discovered in 1940 but didn't get much attention because it doesn't make you feel high like THC.
The structure of THC was discovered in Israel in 1964 by scientists named Mechoulam and Gaoni. At the time, the commonly accepted idea was that THC alters the behavior of cell membranes. Over the following years, many scientists studied these cannabinoids to understand how they affect the body.
In 1988, scientists used a compound named CP55940, labeled with a radioactive substance, to detect these receptors in rat brain tissues. This experiment showed the rat's brain had high-affinity receptors interacting with CP55940—like a magnet that attracts molecules very strongly.
The following contributions advanced our understanding in the next decade.
- In 1990, scientists made a breakthrough in genetics by successfully cloning the CB1 receptor in rats and humans.
- Two years later (1992), Dr. Mechoulam's laboratory identified a significant component of the human nervous system (anandamide).
- In 1993, a researcher from Cambridge University in England successfully cloned the CB2 receptor, which plays a crucial role in the immune system.
- Finally, in 1995, Mechoulam's lab discovered 2-AG.
When studying the human body's nervous system, you learn about the autonomic nervous system. This system helps balance the body and comprises the sympathetic and parasympathetic nervous systems. However, there is more to balance than just these two parts, and the body has its ways of balancing itself.
As Dr. Larian recalls from his time in medical school, “We didn’t understand about balance quite so well; we weren’t educated on how your body balances itself. There’s so much magic that our body has.”
The endocannabinoid system is a microscopic balancing that helps keep everything in harmony. This system regulates various vital bodily functions and is not limited to sleep, appetite, mood, and pain.
Benefits range from the wide range of chemical discharges called endocannabinoids that bind to specific receptors throughout the body. When these receptors are activated, they help restore balance in the body by reducing inflammation and promoting relaxation and other functions.
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