The Endocannabinoid System 🧠

Your Body's Secret Messaging System

Meet Jo Cameron. She's a schoolteacher from Scotland who's never experienced being anxious, did not feel pain giving birth and did not know her skin was burning until she smelled her own flesh. She displays no measurable fear response. This is not fiction, this is real.

For most of her life, she didn't realise she was different, until doctors noticed something strange. After major surgery, she needed zero painkillers. Scans showed severe joint damage she'd never even noticed. Turns out Jo has a rare genetic mutation that knocks out a key enzyme in her Endocannabinoid System, the one that normally breaks down "feel good" compounds we re about to discuss.

So instead of her body clearing them out, her system lets them build up. What did that do? Basically made her untouchable to stress and immune to pain.

Wild, right?

Now imagine this: if removing one enzyme from the Endocannabinoid System can do all that… how important do you think the rest of the system is?

That's our Endocannabinoid System (ECS) for short, a secret messaging system inside your body that regulates learning, memory, sleep, temperature control, emotional processing, pain control, inflammatory and immune responses. Sounds like it could be important?

Never heard of it? Don't worry, you're not alone.

It's mad to think we uncovered one of the body's most important systems, all because scientists were allowed to start studying cannabis.

Despite its massive impact on human health, the ECS has remained one of the best kept secrets in biology.

Let's fix that.

How the ECS Was Discovered

The endocannabinoid system was discovered just 36 years ago in 1988. You might be older than the discovery itself.

Scientists weren't exactly looking for it when they found it. They were studying THC, the primary psychoactive compound in cannabis, to see how it interacts with animals on a chemical level. They were in for a surprise.

They started by asking a simple question: when animals consume cannabis, specifically THC, where does it go, and what does it actually do?

What they found was that THC didn't just float around aimlessly. It locked onto specific sites in the body, membrane receptors.

But here's where things got interesting.

While tracking THC's effects, scientists noticed something unexpected. There were these other compounds they had never seen before, that were binding to those same receptors. Only these compounds weren't coming from the cannabis plant.

So what were they and where were they coming from?

Short answer. They come from us. Not something we consume, but something we create inside us.

What scientists discovered were endogenous cannabinoids i.e chemical compounds found inside the human body, already naturally being produced within us.

THC & CBD are exogenous cannabinoids i.e chemical compounds found outside the human body, from another living organism, that we consume.

Our own body has THC, CBD like chemical compounds, already being made inside us. Turns out, our bodies naturally produce their own cannabis like compounds and we hadn't a clue about it.

So to clarify

• Exogenous cannabinoids = Compounds from outside the body (like THC or CBD that come from the cannabis plant).
• Endogenous cannabinoids = Compounds already inside your body, naturally being produced by you.

Turns out the 'gateway drug' was actually a gateway to understanding human biology.

This was the discovery of a whole signalling system inside us that consisted of cannabinoid receptors, endocannabinoids and enzymes. The ECS as we now know it. A natural communication system working to regulate learning, memory, emotional processing, sleep etc, undiscovered until 36 years ago. It's one of the most important physiologic systems involved in establishing and maintaining human health. Pretty cool recent discovery.

So on behalf of those who've spent years advocating for this plant, helping break the stigma and showcasing this plant might not be as bad as once thought, this one's for the 'demon drug' crowd.

How the Endocannabinoid System Works

The endocannabinoid system is like your countries post/mail service. There's two teams, the postmen and the post boxes. The postmen deliver the message and the post boxes receive the message. They communicate inside you. It's a chemical communication system.

The postmen are what we call endocannabinoids. Endocannabinoids are the postmen that go around your body, talking to your brain, immune system, and organs. They have a message to deliver.

The post boxes are what we call our receptors. Your brain, immune system and organs are filled with these receptors. These receptors are even in your skin, mad to think. The postmen deliver their message to these post boxes and a chemical reaction occurs inside us.

Their jobs are to keep everything balanced and working smoothly. Something is up? The endocannabinoids are actual messages that get sent to your receptors across your brain & body, to fix whatever is up.

They tell your body when to eat, when to sleep, when to relax, and even when to feel happy or less worried. It helps your body know when things are okay or when something might need attention.

For example, if you get a bump or a scrape, the endocannabinoid system will send messages to help your body feel less pain or to reduce swelling/inflammation. Or when you're feeling anxious or nervous, the endocannabinoid system can send messages to help you calm down and feel more relaxed. Like when you take a deep breath to feel better. It's like a helpful team inside you that makes sure everything is working as it should. And remember these are all natural compounds that exist inside us already. No cannabis involved here.

It's primary role is to maintain homeostasis for us. Homeostasis is the process by which living organisms maintain a stable internal environment despite changes in external conditions. This balance is crucial for survival and proper functioning.

So, the endocannabinoid system is basically your body's own special team that sends messages around you, which helps you feel good and stay healthy every day! Cmon the endocannabinoids! Nate little fellas. Fair play to ye.

Seems like it could be a really interesting and significant discovery that can hopefully have a positive impact on us humans. In the 1720's our life expectancy was 28. In 1900 it was 32. Mad.

The ECS is present in humans, animals, trees, plants but not insects.

So let's dive into this some more and get a wee bit technical.

The ECS has 3 Main Components

Discovery timeline of the ECS | Source: Project CBD

1. Membrane Receptors

• CB1
• CB2

2. Endocannabinoids

• AEA (anandamide)
• 2-AG ( 2-arachidonoylglycerol).

3. Enzymes

• Fatty Acid Amide Hydrolase (FAAH)
• Monoacylglycerol Lipase (MAGL)

The receptors & endocannabinoids act in a key & lock model inside us. What this means is that only certain keys can unlock certain locks. Only certain endocannabinoids can unlock certain receptors. If the postman is delivering the post to the wrong postbox, ain't nothing gonna happen.

Think of it like this:

• Endocannabinoids are the keys.
• Receptors are the locks.

I know it's another analogy but it's more so the postman/postbox analogy helps with the concept of a chemical communication messaging system and the key and lock analogy goes a bit deeper and explains how targeted the interaction is, within the chemical messaging system.

The key must fit the lock to achieve the desired result. So the endocannabinoid must fit the receptor to achieve the desired result.

1: Endocannabinoids (Keys / Postmen)

These are the "naturally occurring cannabis like compounds" that are being made by our cells every single day.

As discussed above when scientists were examining THC, they came across cannabinoids already being naturally produced inside us. These endocannabinoids (keys) are the mailmen running around our body with important information to deliver. Once they deliver their message to the right receptor a chemical reaction occurs.

The two main established & studied endocannabinoids inside us are

• AEA (Anandamide) - Also known as the "bliss molecule." Responsible for that post run euphoria, aka "runner's high"
• 2-AG (2-Arachidonoylglycerol) - Helps maintain overall balance in the body (homeostasis).

Anandamide (AEA)

Imagine this.

You wake up, lace up your favorite running shoes, and step out into the fresh morning air. Your feet hit the pavement, one step after another, and before you know it, you're in the zone. That wave of euphoria washes over you, a rush of joy, clarity, and calm. This feeling, often called a "runner's high," is more than just a motivational buzz. It's your body's natural endocannabinoid system at work, releasing a special molecule called anandamide (or AEA for short).

When you start running, your body produces more AEA. This molecule floats around until it finds a receptor to lock into, specifically the CB1 receptor, part of your endocannabinoid system. Think of it like a key fitting perfectly into a lock. Once AEA connects with CB1, it triggers a chain reaction in your brain that releases dopamine, the feel good chemical.

You've probably heard about dopamine before, it's that feel good chemical that helps you feel happy, motivated, and sometimes even a little euphoric. When THC, the active ingredient in cannabis, attaches to CB1 receptors in your brain, it can boost dopamine levels quite strongly, which is a big part of why cannabis gives you that intense "high." On the other hand, your body's own natural molecule, anandamide (AEA), also connects with those same CB1 receptors but in a much gentler way. The rise in AEA during a good run gives you a softer, more natural "yeah, that's awesome" kind of high, enough to make you feel great without overwhelming your brain.

So, in a way, your body is giving you a natural high, no drugs needed! It's your own built in feel good system, rewarding you for moving your body and keeping you motivated to do it again. Who needs drugs when we can just run eh?

2-AG (2-Arachidonoylglycerol)

But life isn't always about blissful runs and dopamine rushes. Sometimes, you trip or hurt your neck. You scrape your knee. You feel pain. That's where another endocannabinoid superhero comes into play: 2-AG.

While AEA is more about mood and euphoria, 2-AG takes on a different mission. It locks into the CB2 receptors, which are found throughout your immune system. Think of 2-AG as your body's natural first aid kit. When you get hurt, 2-AG jumps into action, sending messages to reduce inflammation and manage pain.

Picture this: You've just banged your knee on the edge of the coffee table. Your body doesn't just sit there and let you suffer. Instead, it kicks into action. 2-AG molecules increase in production, find the CB2 receptors, and start working to calm the swelling and ease the pain. It's like your body's personal pain management system, ensuring that you heal and feel better naturally.

Understanding these natural processes makes you realize just how incredible your body truly is. You don't always need external substances to feel good or manage pain. Your body has a sophisticated system designed to do just that.

So, the next time you go for a run and feel that post exercise buzz, remember that it's not just in your head, it's your body releasing its own version of happiness through anandamide. And when you bump your knee or feel sore, know that 2-AG is quietly working behind the scenes to help you heal.

2: Receptors (The Locks / Postboxes)

So we talked about the keys. Let's discuss the locks now. Our receptors.

There are two main types of receptors in the ECS:

• CB1 receptors — Found mostly in the brain and central nervous system.
• CB2 receptors — Found mainly in the immune system and peripheral organs.

They receive the messages from our cannabinoids.

CB1 Receptors

CB1 receptors are primarily found in the central nervous system, with high concentrations in brain regions such as the amygdala, hippocampus, cerebellum, basal ganglia, frontal cortex, and brainstem. They are also present in peripheral tissues like the liver, lungs, kidneys, and peripheral nerves.

CB1 receptors play a crucial role in regulating neurotransmitter release, which affects processes including memory, appetite, pain sensation, mood, motor control, and cognition. Activation of CB1 receptors by endocannabinoids or compounds like THC (the psychoactive component of cannabis) produces the characteristic psychoactive effects and helps modulate pain and appetite.

CB1 receptors are crucial for brain functions and psychoactive effects.

How cannabis interacts with CB1 receptors.

CB1 receptors are the primary target of THC. THC goes looking for CB1 receptors. Once THC binds with CB1 a chemical reaction occurs.

Let's take a look at the euphoric sensation that occurs due to this. THC enters our system, binds to CB1 receptors located in our brain, which releases dopamine into our system.

Dopamine is famously known for giving you feelings of pleasure, satisfaction & motivation. So when cannabis is ingested by humans, excess levels of dopamine are sent throughout our body making us feel all these good things. We get motherfucking highhhhh. Great! Right? Yes, but not entirely.

This is where lies the potential for the drug to be abused. Some people out there say cannabis isn't addictive. I disagree. I would say it 1000% can be addictive for sure. If it's releasing dopamine at a higher level than normal then the potential for it to be repeatedly abused is present. This is where we have to be aware of what's happening and make educated decisions when dealing with life situations like this.

Also maybe if you're thinking "see cannabis is addictive so it should be banned", nah. Ban caffeine, alcohol, mobile phones, gambling and sugar while we are at it. Comparing isn't the right way to do this either. But is there not just a sneak peak of common sense popping its head around the corner? Maybe cannabis in the grand scheme of world operations, is ok?

It's a whole other topic of conversation that I will save for another day. I personally believe all drugs can be addictive. They take us away from the constant state of reality and people chase it. With weed it will take over your life and become the main focal point of each day, which should not be the case with any drug. There's more to life than waiting for you the whole day to pass and then have a joint.

We have to accept and understand this and not shy away from it. Accept it and act accordingly. Animals including humans have knowingly consumed drugs through history right until this present day. Humans gonna human.

CB2 Receptors

CB2 receptors are mostly found outside the brain, predominantly on immune cells such as T cells, B cells, macrophages, and microglia in the central nervous system. They are also expressed in peripheral tissues including the spleen, liver, and certain neurons. CB2 receptors are primarily involved in regulating immune responses, inflammation, and pain relief without producing psychoactive effects. Their activation helps modulate inflammation and immune cell function, making them a promising target for anti-inflammatory and neuroprotective therapies.

CB2 receptors mainly regulate immune system activity and inflammation.

Research into CB2 receptors continues to uncover their potential therapeutic applications, particularly in the fields of immunology, neurology, and inflammatory diseases. There appears to be great potential with these receptors in the medical world.

This is the fall, graze your knee example we discussed above. Once you fall and graze your knee your body will send endocannabinoids to your CB2 receptors to reduce swelling & inflammation.

How cannabis interacts with CB2 receptors.

Let's imagine you have a friend with rheumatoid arthritis. Their immune system is causing inflammation in their joints. When they consume cannabis, cannabinoids from the plant lock onto CB2 receptors and send a message to calm down the immune system, reducing pain and swelling. When the cannabinoids lock into these CB2 receptors, they tell the immune cells to calm down. They help reduce the inflammation and make the joints feel less painful and swollen.

So, in simple terms, the cannabinoids from cannabis can help your friend's sore joints feel better by calming down their immune system's reaction.

3: Enzymes — The Cleanup Crew

Finally, we got enzymes.

These lads show up after the magic happens, after anandamide has locked into CB1 and released a bit of dopamine. Endocannabinoids don't just stop on their own. They need to be stopped. That's where enzymes step in: to clean up, break down, and shut off the signal. They facilitate the breakdown and metabolism of endocannabinoids. The degredate them. They destroy them.

Enzymes are the cleanup crew, the bouncers, the bin men, the reset button. Without them, your system would be buzzing 24/7 with no off switch.

The two enzymes that degradation our endocannabinoids are:

• FAAH (Fatty Acid Amide Hydrolase) — Breaks down anandamide.
• MAGL (Monoacylglycerol Lipase) — Breaks down 2-AG.

So pretty much the enzymes clean up the endocannabinoids that are unable to stop by themselves.

And if you want to see what happens when that cleanup crew doesn't show up? Look no further than Jo Cameron. Her FAAH enzyme doesn't work properly, so her anandamide levels stay sky high. That means her body is constantly awash with natural painkillers and mood stabilisers. It's like her system's permanently set to "chill mode." No fear. No pain. No bother. She literally only realised something was off when she was well into her 60s. Think about how that flips the entire conversation around pain, mental health, and cannabis research.

BUT, when we consume cannabis it goes a little different.

Consuming cannabis changes the game with how our enzymes work. Compounds like THC and CBD interact with these enzymes and can inhibit their activity. In simple terms, they prevent the cleanup crew from doing its job. This means endocannabinoids like anandamide and 2-AG aren't broken down as they normally would be.

This is most relevant when we talk about CBD. Listen to this shit.

One of CBD's key actions is inhibiting the enzymes as discussed. By slowing down these enzymes, CBD allows more of our body's natural endocannabinoids to remain active for longer. This enhances the effects of our endocannabinoids, helping to support mood regulation, reduce inflammation, and promote balance across various systems.

In other words, CBD doesn't replace what your body does, it helps your body do what it already does, just a little better.

On a side note, that enzyme fella up above, he looks well annoyed. Definitely Italian. Might've just been told his shift was cancelled. He'll be grand.

While cannabis compounds offer benefits like reducing inflammation and enhancing mood, they also highlight the delicate balance enzymes maintain in our system. Enzymes ensure naturally occurring cannabinoids are efficiently processed and cleared, but they struggle to manage the exogenous compounds introduced by cannabis.

So that's it. At a basic level, how the ECS works without diving into, electrical impulses, presynaptic nerves, calcium influx, acid, battery acid, salsa, bang and the dirt is gone, some herbs and spices, all wrapped in a tortilla.

Gluck.

References

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