The Endocannbinoid System: Figuring out how Cannabis works in the Body

Since the endocannabinoid system (ECS) is a relatively new scientific discovery, many traditional medical professionals still don't know much about it or how important it is to keeping our bodies in balance. The endocannabinoid system is a full-body signaling network with receptor sites CB1 and CB2 that are set up to respond to cannabinoids. It is found in all humans, animals, plants, and fungi (basically anything with a cell structure that has a membrane around the nucleus). These receptors are in the brain, organs, connective tissues, bones, glands, and immune cells. The ultimate goal of turning them on is to keep the body in homeostasis, or a stable state, to avoid getting sick. Our health depends on having a well-balanced endocannabinoid system. This system affects inflammation, pain, appetite, and mood. In fact, if we fully understood the endocannabinoid system, we could find ways to treat almost all diseases. Cannabinoids are present in our bodies from the time we are born. They help with fertility and are found in breast milk. Throughout our lives, cannabinoids continue to play important roles in our survival, such as controlling stress, anxiety, and appetite and protecting neurons to slow the progression of disease. The ECS controls our bodies and moods by letting different types of cells talk to each other and work together.

Jahan Marcu, editor and chief of The American Journal of Endocannabinoid Medicine, says, "How well we can use what we know about the ECS will have a big effect on medicine and our health as we try to make sense of a world that is getting more and more chaotic and stressful." "Since the beginning of time, the ECS has helped humans adapt and overcome problems that seemed impossible to solve. Scientists hope that their new understanding of the ECS will continue to improve our ability to deal with stress while keeping our health. The more we know about the ECS, the more likely we are to do well and stay alive.

Cannabinoids work like neurotransmitters, which are chemicals that send messages between nerve cells (neurons) in the brain, nervous system, and immune system. There are two kinds of cannabinoids that interact with the body's own receptors: endocannabinoids, which are made by the body, and phytocannabinoids, which come from the cannabis plant. Synthetic cannabinoids are also made in labs by scientists.

History of the Science of Cannabinoids

Cannabis has been helpful to people since ancient times, but it wasn't until the 1930s that cannabinol, a chemical found in cannabis, was found and isolated (CBN). In the 1940s, scientists found and isolated cannabidiol (CBD), which is another type of cannabinoid. This brought them closer to isolating tetrahydrocannabinol, which is the most well-known cannabinoid (THC). The first person to study cannabis was Raphael Mechoulam. In 1963, Mechoulam, an Israeli biochemist, found out more about how CBD is put together. In 1964, he and his colleagues made a big step forward when they found and isolated THC, the most well-known cannabinoid.

By the 1980s, scientists were getting a better idea of how plant cannabinoids worked, but they still didn't know exactly how they did what they did. Scientists thought that the chemicals in cannabis must interact with a receptor in our bodies, but it wasn't until the late 1980s and early 1990s that they found the CB1 receptor and then the CB2 receptor. CB1 receptors are mostly found on nerve cells in the brain and spinal cord, while CB2 receptors are mostly found on immune cells. Cannabinoid science made a big step forward when researchers found that the psychoactive effects of THC interact with the CB1 receptor.

In an article for O'Shaughnessy's, a magazine about medical marijuana, cannabis author Martin Lee says that cloning the cannabinoid receptor was very important. "This gave scientists the chance to make molecules that "fit" these receptors like keys in a slot. Some keys, called "agonists," turned on the receptor, while others, called "antagonists," turned it off.

"By following the metabolic pathways of THC, scientists found a unique and previously unknown molecular signaling system that controls a wide range of biological functions," says Lee.

The endocannabinoid system (ECS) is an internal signaling system found in all animals except insects. It has been around for a long time, which helps show how important it is. In 1992, Mechoulam and his colleagues made another surprising discovery: an endocannabinoid, which is a cannabinoid made by the human body. The name "anandamide" comes from the Sanskrit word "ananda," which means "happiness." It showed that cannabinoids made by the body worked as part of a whole-body system and helped find out how cannabinoids made by plants can also connect to these networks.

"I think there are more than a hundred cannabinoids in plants," says Mechoulam. "There are also a very large number of anandamide-like cannabinoids made by the body itself."

The Molecule of Joy

Anandamide was a great discovery because it shows how our bodies control the ECS from the inside: Whether or not we use cannabis to boost it, the ECS is an important part of our health. When the chemical anandamide binds to the cannabinoid receptors in our bodies, it makes us feel happy. When we exercise, our bodies make a chemical called anandamide. This chemical is what gives us the "runner's high" feeling, which is both exciting and happy. Our endocannabinoid system interacts with the parts of the cannabis plant that make us feel good, but it can also be boosted by other activities and plants. The ECS can also be turned on by massage, exercise, and eating leafy greens that are high in caryophyllene and foods that are high in omega-3s. After anandamide was found, a second endogenous cannabinoid called 2-arachidonoylglycerol (2-AG) was found. We don't fully understand how 2-AG works yet, but we do know that it helps keep the circulatory system in check.

The Effect of Entourage

The idea behind the entourage effect is that cannabinoids and terpenes work best when they work together. This widely accepted theory says that the effects of cannabis come from the way its properties work together. This explains why synthetic forms of cannabinoids, like Marinol, which is a form of THC, don't work as well as medicines that use other chemical parts of the plant.

Using this theory as a marketing tool, many cannabis oils and tinctures advertise "full-spectrum" extracts. This means that the product contains a wide range of cannabinoids and terpenes. The idea is that these products keep the plant's full benefits and are better for you because of it.

Cannabinoids: Making New Ones

Cannabinoids are found in the resinous, tiny, mushroom-like heads (called trichomes) on the flowers and leaves of the cannabis plant. In 2019, scientists at UC Berkeley said they had made cannabinoids from yeast, which meant they no longer needed to work with the plant. Researchers said that they could make new kinds of cannabinoids by changing the yeast so that it turns fatty acids into cannabinoids. The idea behind making cannabinoids through fermentation was to make it easier, cheaper, and more reliable for companies to make cannabinoids than by growing them on plants.

Clinical Cannabinoid Deficiency

The idea of a "critical cannabinoid deficiency" was first proposed in the early 2000s. It is based on the idea that a lack of cannabinoids causes conditions like migraines, IBS, fibromyalgia, and clinical depression. These common conditions don't have clear symptoms and often happen at the same time. Clinical cannabinoid deficiency is based on the idea that the body isn't making enough cannabinoids to keep systems in their natural balance. To maintain homeostasis, cannabinoids should be taken as a supplement.


The discovery of the endocannabinoid system completely changed the game and led to the creation of groups whose mission is to spread the word about the new field of endocannabinology. A group of activists called the Alliance for Cannabis Therapeutics, which was started in 1981, was already looking into how cannabis could be used as medicine. Out of this group came a new group called Patients out of Time, which started holding regular conferences in 1995. The International Cannabinoid Research Society was a more exclusive group made up of the most well-known cannabinoid researchers from around the world. It is a group of about 650 scientists and botanists who work together to study the ECS. It was founded in 1992. The goal of the group is to spread scientific research about cannabinoids and be a source of information about the chemistry, pharmacology, and medical uses of cannabis. The organization holds annual conferences all over the world and puts out a journal that covers a wide range of studies on both humans and animals.

Even doctors are starting to see how cannabis can help people. In 2006, a small group of dedicated nurses started the American Cannabis Nursing Association (ACNA) to represent the new field of endocannabinoid therapeutics to professional nurses. This gave them the tools they needed to understand patient needs and speak up for them when it came to the ECS. The ACNA teaches nurses things like how to give the right dose and how cannabinoids work with other drugs.