A woman once came up to me in a café and asked me what I was reading.

“I’m reading about the brain and neuroscience,” I replied.

“Do they have it all figured out yet?” she asked.

“Well, we used to think different parts of the brain were responsible for particular things, and now we’re learning how networks of brain regions work together to produce complex functions …
But no, they don’t have it all figured out.”

“You know,” she said, “the Bible says we are fearfully and wonderfully made.”

Somehow, she seemed a step ahead of me.

There’s a refrain you hear in the health and fitness world from time to time that goes something like this:

“If exercise were a drug, it would be the best-selling one of all time."

It's a catchy slogan.

And tries to tell a story by packing a lot into a soundbite.

But maybe that's okay.

After all, who can fully understand the vast complexity inside our bodies?

Can human beings really capture everything exercise does, identify the body systems that interact, and create a map of reality?

Maybe ignorance is bliss!

Bliss.

Would you believe there is even a system in the body that has an unusual connection to that word?

Most people have never heard of it.

It's called: the endocannabinoid system.

Scientists discovered it studying a drug.

And that body system is sometimes triggered by exercise.

Exercise and the Mind

It never ceases to amaze me how, time after time, exercise has the ability to shift how humans feel mentally and emotionally.

I’ve experienced it personally thousands of times.

But, often, it still seems like magic.

Surprisingly, science does not fully understand the mechanisms that cause this phenomenon.

Why does exercise have the ability to make people feel dramatically different?

It's a fascinating problem scientists have been trying to solve for almost half a century.

Maybe we should call it a day and conclude it's caused by elves.

Subjective states of feeling can be tricky to quantify, so much that some scientists think we don’t really know how a subjective state emerges from physical matter.

As neuroscientist Robert Sapolsky suggested, sometimes you can't understand human behavior by taking it apart like a clock.

That said, according to where scientific thinking is at today, part of the effect may be due to changes in human biochemistry.

And probably a combination of factors.

Popular culture often touts the value of exercise.

But far less commonly do people hear details about the biochemical changes that take place during exercise.

In this article we'll dive a little deeper into taking a look at things.

And while it’s not possible to fully explain the causes, or cover all the details, (especially in this type of article) at least we can find out a bit more about what is going on under the hood.

It's possible some of the changes we observe in how people feel during and after exercise could be due to endorphins and the endocannabinoid system.

Endocannabinoid is a fancy-sounding word.

But what does it mean, really?

And why do scientists think it might play a role in how we feel when we exercise?

Note: The endocannabinoid system isn't a brain-only system.

Endocannabinoids and their receptors are distributed throughout the body, in many tissues.

Who Was the God of Dreams?

Marijuana has been part of human culture for thousands of years.

Long before modern science, people knew it had noticeable effects on the mind and how people felt.

Marijuana comes from the cannabis plant.

The word cannabinoid comes from the word cannabis.

THC is one of the best-known compounds in cannabis.

It is responsible for many of the plant’s psychoactive effects, the "high" feeling people get.

But scientists discovered something remarkable: our bodies actually make their own cannabinoid-like chemicals.

These substances are called: endocannabinoids.

That’s because “endo” means inside.

For example: inside the body.

The nomenclature is not that different from opioids.

Opioids are a class of molecules (often found as both legal and illegal drugs) that work in the brain and nervous system to produce a variety of effects, including pain relief.

Opioids can come from outside the body, For example, morphine from the flowering plant known as the opium poppy.

Or the body can internally make its own opioids.

hese are referred to as: endogenous.

Hence our word endorphin, coined in the 1970s:

endogenous + morphine = endorphin

Fun fact:

Endo comes from the Greek endon, meaning "within.”

And morphine is named after Morpheus, the Greek god of dreams.

Have you ever heard of someone saying they got an "endorphin rush" from exercising.

Well, that may not be technically correct, or if so, only partially.

What do we know about these substances generated inside our body that impact how we feel?

And more specifically, what do we know about the endocannabinoid system and its relation to exercise?

To look at that it helps to get a clearer picture of what scientific discovery looks like, and how it unfolds over years.

As you will see, science doesn't necessarily discover a thing, then immediately understand what it is for.

Given how long humanity has been around, much of the science we hear about that is related to fitness and exercise is relatively new.

And science itself accrues in pieces!

To use a simple metaphor, imagine you discover something.

It looks like some kind of lock mechanism.

But you're not sure what it is, or what it does.

Maybe it does many things.

Years later, you figure out it's a door knob to a house.

And years later you find a key that fits that lock.

Consider these examples in science.

Ghrelin, a hormone, was discovered in 1999.

Then, slowly, its role in sending hunger signals to the brain was pieced together.

However, earlier discoveries about systems that ghrelin turned out to be part of had been unfolding as far back as the 1960s.

Endorphins were "discovered" in 1975 (the key).

However, Candace Pert, Sol Snyder, and Eric Simon were already identifying the relevant opiate receptors (the lock) in the brain as early as 1973.

And in 1965 a hormone called beta-lipotropin was found.

Except, no one knew what it did!

It would later turn out to be a precursor to β-endorphin (and other peptides).

So, endorphins came on the scene in the mid 1970s.

In 1979, Australian professor Gary Egger, having observed from personal experience that long-distance running seemed to reduce pain (or more correctly, increase pain tolerance) conducted an experiment using an opioid-blocking drug and a placebo.

The results suggested that while exercise could increase his pain tolerance, endorphins might not be the whole explanation.

Through the 1980s, researchers looked at endorphins to try to explain the phenomenon we now call the “runner's high.”

But increasingly, it appears that science is discovering that the experience of exercise-induced feelings of well-being involves multiple signaling systems.

That said, keep in mind that finding a substance (i.e endorphins or endocannabinoids) circulating in the blood, doesn't tell scientists if, why or how it impacts the brain.

And it's worth remembering that exercise is a whole body experience.

It has many effects on the body.

For example

it changes heart rate,
Affects muscles, the position of our joints and the sensory information registered by the brain
alters how the body utilizes oxygen,

among many other things.

So, it can be important not to overstate the potential contribution of biochemistry alone, or of any one chemical.

Biochemistry itself is embedded in a larger biological event.

If you enjoy deep dives into health and wellness, you might find this article interesting.

If you want a short, clear summary, you might find useful this article from 2022, by Dr. Hilary Marusak, a neuroscientist and Associate Professor of Psychiatry and Behavioral Neurosciences at Wayne State University School of Medicine.

And of course you can always skip reading anything at all and chalk it up to elves.

A Few Thoughts on How to Read This Article

The first stop on our more detailed intellectual adventure is: lipids.

Then we will circle back to exercise and feeling good.

You've absorbed a lot.

To get the most out of this article you might consider reading it in pieces over the next few days.

That way the brain gets a workout, but you can pace yourself.

Fair warning, this is a lot to absorb in one sitting.

Podcast Excerpt:

Nathan Schechter: It sounds like you're talking a bit about the ease of belief, that some people just want it to be easy, so you can latch onto a simple model, and then if you latch onto a simple model, you just say, well, that's how it is.

Even if that's not really how it is, or it's misapplied, it's just easier than doing the work to understand something more, and that you run into that a lot.

Most folks have probably never heard too much about lipids.

However, a lipid many people know the name of is cholesterol.

Another member of the lipid family many people have heard about are fats.

At least fats that we eat.

But the body uses fats in a host of ways. They aren’t just found in food.

For example, fats and lipids are a major component of the make-up of the membranes of your cells.

And that points out that lipids can act as structural and signaling molecules, not just energy storage.

Interestingly, dietary fats take a special route through the body after digestion.

When dietary fats are broken down into fatty acids, after we eat them, many of them eventually hitch a ride through our bodies along with cholesterol. (We won't get into the role of chylomicrons here.)

Long-chain fatty acids, which can’t move through the blood stream on their own, have to hitch a ride on lipoproteins (or attach to proteins like albumin) just like you might ride an inner tube down a river ride at a water park.

One day during my nutrition studies, I started to wonder whether deliberately consuming fats that are more rapidly transported to the liver might provide a quicker energy boost before exercise.

Unlike long-chain fatty acids, short-chain and medium-chain fatty acids can be transported directly to the liver (through the portal vein).

In search of greater understanding, I went looking for experts.

Over the last few years I had the chance to talk in depth with a number of lipid biochemists, and it taught me a lot.

During this time I started to understand more about lipids, which, as mentioned earlier, make up a major part of all of our cell membranes.

Dr. Daniel Guerra pointed out to me that while science now knows the sequence for human DNA, no one has a sequence for cell membranes.

His point was that cell membranes are not just barriers like we learned in high school. They are communication networks!

Ones that are part of extremely complex, real-time events in the body.

Speaking with Dr. Guerra changed how I understood a number of things, including that the body may better be thought of as an EVENT, rather than the way most of us perceive it, as a static thing.

You can listen to my conversation with Dr. Guerra on the Mind Body Literacy podcast HERE.

Searching for an Explanation

So what does all this have to do with how great a person may sometimes feel after exercise?

Think about the human experience.

A person feels tired. Or aggravated. Or sad. Or any human emotion.

Then they do some weight lifting or running.

And an hour later they feel completely different.

It may not be elves.

But, it may be lipids!

The endocannabinoid system, which has numerous functions, is a highly complex microscopic network of signaling lipids, receptors, and enzymes discovered in the late 20th century that acts on demand to help regulate the body,

And the endocannabinoid system is one plausible contributor to the post‑exercise “high.”

Yoga fans may be intrigued to learn that one of the substances being studied in connection with these good feelings has a name taken from Sanskrit, anandamide, after the Sanskrit word ānanda, meaning “bliss” or “divine joy.” (It’s often abbreviated AEA.)

And wouldn’t you know it …

Anandamide is an endocannabinoid lipid!

For a long time scientists thought endorphins were largely responsible for the post-workout high.

But it’s no longer so clear that that is the full story.

For example, as shown here:

Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans
https://pubmed.ncbi.nlm.nih.gov/33582575/

And here:
Do Endocannabinoids Cause the Runner’s High? Evidence and Open Questions

https://pmc.ncbi.nlm.nih.gov/articles/PMC10159215/

What we think we know is that, as your body responds to exercise, a combination of physiological signals can stimulate cells, including neurons, to produce endocannabinoids.

These cells can then synthesize endocannabinoids like anandamide from lipids in their own cell membranes.

THC & Endocannabinoids as "Keys"

What is startling is that both anandamide and THC can activate cannabinoid receptors, especially CB1 receptors in the brain.

For simplicity think of receptors as different locks on different houses.

Then, in this very simplified metaphor, think of molecules that fit with these receptors as keys.

Both the external substance (THC) and the internal substance (endocannabinoids) act like keys, fit the lock, and impact the body.

Once the CB1 receptors are impacted they act somewhat like volume knobs.

They can can decrease the release of excitatory neurotransmitters such as glutamate.

This is one of the ways endocannabinoid signaling might influence processes involved in pain perception, anxiety, and other aspects of brain function.

It's thought endocannabinoid signaling also impacts other systems involved in reward and motivation, including dopamine.

Fading Feelings and The Clean Up Crew

But as experienced exercisers can tell you, the “bliss” doesn't just accumulate indefinitely.

That’s because the body has a "cleanup system."

Because anandamide is a relatively short-lived molecule, an internal metabolic enzyme called FAAH (Fatty Acid Amide Hydrolase) helps break it down.

Interestingly, the brain doesn’t simply store endocannabinoids like many traditional neurotransmitters (i.e. in vesicles.)

Your brain isn't carrying around a little bottle of anandamide waiting for you to go for a run.

Your cells can make it when they need it, in real time when the body receives the appropriate signals.

And want to know one more strange science fact about endocannabinoids?

Unlike traditional neurotransmitters that generally signal forward from one nerve cell to the next, endocannabinoids like anandamide can signal in the opposite direction.

This is called “backward” signaling, or retrograde signaling, where the receiving cell sends a signal backward to the sending cell.

Think of it like the receiving cell saying, “Okay, that's enough.”

Endocannabinoids in Different People and Exercises

Current thinking, based on a handful of studies, is that the endocannabinoid response isn't the same for every kind of movement.

For example, light walking may not produce the same response as more demanding exercise.

Some studies suggest that moderate-intensity aerobic exercise, something like steady jogging, cycling, or swimming, for around 30 minutes, might be able to increase levels of some endocannabinoids in the bloodstream.

But very intense exercise doesn't necessarily produce a larger response.

And not everyone reacts to anandamide the same way, either.

There can be differences in how strongly or how long the effects occur.

Other things may also affect anandamide levels or endocannabinoid signaling.

So maybe it isn't elves.

Maybe part of the story could be lipids that get triggered when you exercise in certain ways.

I'm not sure that's any less magical.

Maybe the real magic is that, in a complex universe, ignorance isn't bliss.

Maybe greater understanding and greater skill, and the actions that flow from them, sometimes give a person more ability to work with their own body and create change.

Even as, the more we learn about the body, the more complicated and remarkable the underlying reality becomes.

Summary

While we're far from knowing how all of this works, and some of the research is based on animal models, it has drawn considerable interest from the scientific community, with researchers exploring the implications of these interconnected systems.

For example, listen to psychiatrist Dr. Tracey Marks, in a video she published on YouTube, talk about the topic.

We may be learning that in certain circumstances an activity as ordinary as riding a bicycle can initiate a cascade of biochemical events that influence not only brain structure, but how the brain adapts and responds to the world.

And as for endocannabinoids as the singular cause of bliss, or the runner's high, well ...

Reality is enormously complicated.

Maybe it's elves.

Or maybe we really are fearfully and wonderfully made.

Disclaimer

The information and content provided by Mind Body Literacy and in this article is general information and is intended for educational purposes only. Individual situations vary. This content is not intended as, nor should it be used as a substitute for, professional medical or psychological advice, diagnosis or treatment. No guarantee or warranties are made with respect to the accuracy, applicability, fitness, or completeness of the content. This article reflects personal observations, interpretations, and opinions.

Nathan Schechter, ACSM CPT, writes about the mechanics of experience - how people learn, change, connect, and perform under real conditions.

Bliss