Here’s a little story – all about how – your understanding of cannabis is about to get turned upside down.

Here’s why: we (as in, humans, and many animals) have cannabinoid receptors and an endocannabinoid system that processes cannabinoids (like those found in cannabis).

But the first cannabinoid to be discovered was plant-based THC back in the 1960s.

After discovering THC and its’ psychoactive effects on the body, scientists tried to backtrack and explore whether the body made its’ own version of THC and where the whole blissful process took place in our bodies.

What did they find after 20 years?

That’s exactly what we’re going to explore in this article.

You might be wondering, what are cannabinoid receptors? Do they mean we’re programmed to accept and process cannabis in our bodies? How does the whole thing work?

To answer all those questions and more, let’s start with the basic framework: the system that controls it all.

The Endocannabinoid System

The ECS Scale

The endocannabinoid system (ECS) is one of the body’s largest neurotransmitter networks but was only discovered in the 1980’s – two decades after THC. The ECS is always working to achieve balance, or homeostasis, which means maintaining a stable internal environment despite changes in the external environment.

Or, balance for our systems, despite the constant chaos of the outside world.

As you can imagine, this is a crucial physiological system to keep healthy.

At its most simple, the ECS’s communications are composed of messengers and receptors. The brain naturally produces endocannabinoid molecules (like anandamide and 2-arachidonoylglycerol, or 2-AG), which are home-grown messengers that can be found in your brain, organs, connective tissues, glands, and immune cells.

Endocannabinoids, like anandamide, act like the body’s natural THC but have a much shorter effect in the body than THC does. In fact, anandamide comes from the Sanskrit word for “bliss”, making it the body’s natural “blissful” molecule. There are also plant cannabinoids that are found in cannabis (THC and CBD are the biggest), and synthetic cannabinoids, which are lab-created and can be up to 600 times more powerful than THC.

Cannabinoids look for and activate cannabinoid receptors (CB1 and CB2) and when they get together they tell your body to feel a certain way and do certain things. They also affect and regulate the way other bodily systems function, like your immune, nervous, and gastrointestinal systems.

The best way to describe the ECS is as a balancing system (or homeostatic regulator): it sends neurotransmitters (messenger + communication molecules) to all your bodily parts to check that everything is working smoothly and confirm if anything needs to be rebalanced. When it finds a problem, it regulates it by sending further instructions to receptors that adjust how you feel and think.

So, what does it keep tabs on?

  • fertility, pregnancy, and reproductive systems

  • appetite, hunger, and digestive systems

  • sleep,

  • motor control,

  • pain and pleasure,

  • immune function,

  • effects of other cannabinoids,

  • temperature,

  • mood and

  • memory.

Because the ECS underpins most of our body’s systems – like the immune, gastrointestinal, central and peripheral nervous, reproductive, digestive, and more –  it remains a crucial opportunity for many researchers to uncover more answers about the medicinal benefits of cannabis, but woefully understudied. As cannabis moves towards the mainstream, more research to understand receptors and our ECS are sure to come.

The natural “bliss” molecule: anandamide

The Natural "Bliss" Molecule

The body’s best-known endocannabinoid, anandamide, does more than just make you feel “blissful”… it’s synthesized in parts of the brain that are important for:

  • memory,

  • motivation,

  • higher thought processes,

  • movement, as well as

  • pain, appetite, and fertility.

When we understand what role anandamide plays in our bodies naturally, we gain a greater understanding of the possibilities of THC.

Anandamide is the chemical that helps us forget unimportant details, improve our happiness, increase neurogenesis (creates new nerve cells), reward us for a job well done (runner’s high), and battle anxiety and depression.

Researchers believe that if you naturally have more have more anandamide, you have less use for cannabis. But can you imagine if your body wasn’t creating enough?

That’s a lot of crucial functionality for life that can go haywire.

Types of cannabinoid receptors

The types of cannabinoid receptors

Don’t get us wrong, cannabis can and does interact with cannabinoid receptors – but the receptors weren’t created for cannabis. They were created as part of the ECS to receive endocannabinoids (and the messages they send) from your brain. Interestingly enough, these receptors also far outnumber any other receptor found in the brain.

Technically, the ECS is just being supplemented when a person consumes cannabis and their receptors are stimulated. Thankfully, this means that many deficiencies and overexpressions of certain characteristics of disease can be “course-corrected” by plant-based cannabinoids like THC and CBD.

As we mentioned, there are 2 main types of receptors: CB1 and CB2.

Cannabinoid Receptor 1 (CB1) receptors are mainly located in the brain and nervous system, as well as in the lungs, liver, and kidneys. Our natural endocannabinoids and the cannabinoid THC from cannabis mainly bind with CB1 (due to their similar molecular structure), which gives patients relief from pain, nausea and depression, among others.

Cannabinoid Receptor 2 (CB2) receptors are found mainly in the immune system, with a heavy concentration in the spleen and in the gastrointestinal system. CB2 receptors bind best with the endocannabinoid 2-AG and cannabis’ CBD and are involved in the regulation of appetite, immune system functions like inflammation, and pain management.

Scientists are on the cusp of determining a third type of cannabinoid receptor (for CBN), but research in this area is ongoing and inconclusive as of now.

How cannabinoid receptors work

How cannabinoid receptors work

The best way to imagine cannabinoids and their receptors is like a lock and key. When a person consumes cannabis, the cannabinoids THC and CBD (keys) flood your body in search of receptors (locks).

When they find one that fits, the effects of the cannabinoid and the function and location of the receptor “click” together and messages are sent through the rest of your body.

As an example: Taking a dose of CBD oil (which will typically bind with the CB2 receptor) can inhibit your appetite, whereas a THC-rich strain can increase appetite because it binds more readily with the CB1 receptor. Hence why you get “munchies” from certain strains of cannabis, but not from others.

However, the ECS is unique in that it communicates “backwards”: this particular sort of cell-to-cell communication inhibits immune response, reduces inflammation, relaxes muscles, lowers blood pressure, and normalizes stimulated nerves. Basically, our natural endocannabinoids “check” to make sure not too much is happening in your body before accepting more stimulation or the system creating more messages.

What this means is that endocannabinoids are created “on demand” and can act as a “dimmer switch” that affect how quickly, often, and where messages get transmitted.

That’s why the ECS is so crucial to proper functioning and health. Dysregulation of the ECS contributes to a wide variety of conditions that prevent the body from achieving balance, like fibromyalgia or IBS. Whether an overproduction of an enzyme, protein, or an overexpression of receptors, if the ECS isn’t functioning correctly, your body has a difficult time regulating it’s emotions, appetite, memory, and everything else the ECS is responsible for.

Though the lock and key analogy does a good job of explaining the basics, the ECS is more nuanced and complex than scientists can confirm even today. While THC works in line with the lock-and-key analogy (binding directly to receptors by mimicking endocannabinoids), CBD works to increase the amount of endocannabinoids in your system by altering the way enzymes work.

How does it do this?

The FAAH enzyme’s job is to remove extra anandamide from your system by breaking it down (thus decreasing happiness and “bliss”). CBD stops FAAH from doing that, thus leaving more endocannabinoids out for consumption by the rest of your body. This way, not only is there more bliss hanging around, there’s also the effects of the pain-relieving and non-psychoactive CBD.

Balance of CB1 and CB2 receptors

The balance between CB1 and CB2 receptors

Beyond affinity for binding with certain molecules, receptors are also located in different body parts and have different density and numbers, which is considered to be the “expression” of the receptors.

The expression of receptors is as unique person-to-person as their fingerprints: everybody has a different balance, number, and concentration of them, which is why experimenting with cannabis medication is such a delicate and slow process. Different expressions of cannabinoid receptors mean different experiences consuming the same type of cannabis.

The increased density of CB2 receptors in the gastrointestinal system is a great example of why patients with Crohn’s or IBS benefit so much from cannabis medication: CBD-rich medication binds with all the receptors in your gastrointestinal tract and provides pain relief and relief from the inflammation typical in those diseases.

Another example is an over-expression (too many) of CB1 receptors causing a patient to be overly sensitive to THC, leading to munchies or other side effects much quickly than others. If patients under-express the CB2 receptor, they would need to consume greater quantities, other cannabinoids, or specific terpenes along with CBD to feel its’ healing effects.

While cannabinoids have flexibility about the receptors they bind with, having a general understanding of the likelihood (or affinity) for bonding with receptors and their locations, functions, and expressions can help patients have deeper, more meaningful discussions with their physician and come up with stronger treatment plans.

It’s important to keep up-to-date with studies about cannabis that are constantly being updated with findings about receptors, cannabinoids and how they work.

Cannabinoid receptors in action

Cannabinoid Receptors in Action

Knowing about cannabinoids, terpenes, and the endocannabinoid system can only help you get a better grasp of how cannabis affects your body. Scientists that are exploring the endocannabinoid system have found information regarding the following conditions:

Epilepsy

Patients with epilepsy have recently been recommended a CBD-rich, low-THC strain because of its anti-inflammatory properties and its’ bonding with CB2 receptors. The side effects for typical anticonvulsant medications are miles long as opposed to the calming, non-psychactive, and healing effects of CBD.

IBS or Crohn’s

Because CB2 receptors are located densely in the gastrointestinal system (as mentioned above), they are responsible for regulating inflammatory responses for the system – which is good news for patients who use CBD for gastrointestinal issues like IBS or Crohn’s.

PTSD

Patients that suffer with PTSD have had increasing success with THC, due to its’ mimicry of our natural endocannabinoid anandamide. While at first its’ ability to help us forget unimportant details (or mental clutter) is strange, using that functionality to help patients overcome negative memories surrounding a traumatic event and increasing their mood has proven to be very successful and helpful.

General Mental Health

Researchers have found that mice without CB1 receptors show “psychological abnormalities” like increased anxiety and enlarged amygdalas (responsible for emotions and motivation). Genetic studies show that CB1 receptors are important for reducing and controlling anxiety during high-stress periods, so having less or none of these receptors can cause complications.

Reminders about Cannabinoid Receptors

  • Humans come equipped with an Endocannabinoid System (ECS), which include endocannabinoids and cannabinoid receptors, which function like a lock-and-key

  • The ECS underlies and controls the balance of all your other bodily systems by being a great communicator

  • We have 2 different types of receptors – CB1 and CB2 – that are responsible and built for accepting and locking with different types of molecules

    • CB1 is a great fit for anandamide and THC

    • CB2 is generally receptive and activated by CBD

  • Endocannabinoids are naturally produced by our bodies, but we can supplement them by learning more about plant cannabinoids, derived from cannabis

  • When the ECS is dysregulated, your body has difficulty communicating with your brain and vice versa

  • Scientists are discovering new things about cannabinoids and cannabinoid receptors every year, so it’s important to keep up on the latest studies to update your knowledge and inform your health care plan

  • Everybody’s ECS is totally different – like a fingerprint – which is why everyone experiences cannabis in different ways, and why it’s crucial to

start low, and go slow

when experimenting with cannabis.