The Interconnectedness of Sleep, Gut Health and the Endocannabinoid System

Gut Health, Sleep and CBD are all interconnected. Gastroenterologist, Dr. Will Bulsiewics, in his book ´Fiber Fueled Cookbook´ (2022) notes that ¨Research has shown that sleep and your gut microbiota are intertwined. A damaged gut negatively affects sleep. Sleep deprivation negatively affects your gut. It can either work for us or against us. Either way, it’s important to keep track of the correlation between sleep and digestive symptoms because just two nights of poor sleep have been connected to alterations in the gut microbiota.¨

Scientists are still trying to understand the details. But evidence is accumulating that the endocannabinoid system interacts directly and bidirectionally with bacteria in the gut, influencing the activity and makeup of the microbiome while simultaneously helping to transmit its messages to the body and brain. What’s more, microbiome health may be modified and even improved through plant cannabinoids, including both THC and cannabidiol (CBD), as well as through the body’s own endocannabinoids, anandamide and 2-AG, whose production is stimulated through exercise and the consumption of certain foods.

We also know that a dysregulated endocannabinoid system has a negative impact on our gut flora. And that certain foods improve the endocannabinoid function. The endocannabinoid system is being overwhelmed and overloaded with constant signals of stress, pain, inflammation. It’s very difficult under those conditions for it to properly make these endocannabinoids. We need to eat Omega-3 and Omega-6 fatty acids to even make these cannabinoids. A lot of us are deficient in the foods that are essential to even create these endocannabinoids.

At Secret Garden Inspirations, one of our most common first experiences from clients taking a full spectrum CBD dominant herb is their improved sleep patterns. And in a CBD use survey conducted by, participants reported that CBD helped people get to sleep more quickly, reducing the average time from about an hour to 20 minutes. Perhaps more importantly, participants reported waking up less often when using CBD for sleep.

So we can see that there is a distinct interconnectedness between a healthy endocannabinoid system, our gut health and our sleep patterns.

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The ABC´s of CBD

The ABC´s of CBD (excerpted from a Reader´s Digest article-  be forewarned, this is a longish and technical read)

Italian scientist Vincenzo DiMarzo described the role of the endocannabinoid system (ECS) in human health as helping us to “eat, sleep, relax, protect, and forget.”

Let’s take a closer look at these five key functions:

Eat: The ECS helps regulate appetite and satiety.

Sleep: It helps you wind down and get a good night’s sleep.

Relax: The ECS promotes physical and mental well-being by mitigating stress.

Protect: It builds brain cells to protect your brain health, promotes healthy metabolism, and modulates your immune system so that it can fend off harmful invaders.

Forget: Seems like an odd one here but forgetting is an essential component of healthy living. If you remembered every single detail of what happened every second of every day, you wouldn’t be able to function like a sane person. The ECS regulates both essential memory and “memory extinction,” forgetting what’s not important to remember.

How does the ECS do all these things? By acting as a master regulator for your body.


Imagine you’re sitting in a room surrounded by four walls covered with 100 thermostats. Each of these thermostats regulates an essential physiological function that keeps us healthy. Think of the ECS as the sum total of all those thermostats combined into a single, dynamic system that’s involved in regulating nearly all human biological activity.

“Modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans.”

As the master regulator, the ECS controls a broad array of physiological processes like wound healing, blood pressure, pain perception, brain cell production, glucose metabolism, and immune function to control inflammation.

When you’re faced with an emergency situation, you get a surge of stress hormones like cortisol and adrenaline so you can act appropriately — “fight or flight,” as it’s commonly known. Once the threat is no longer present and the situation returns to normal, your ECS turns down the stress response and brings those hormones back to baseline.

Likewise, when you’re sick and you need a fever to fight and kill whatever bug you have, the ECS turns up the heat.

And when the invader is eliminated and you no longer need the fever, the ECS turns down the immune system’s dimmer switch to bring your temperature back to normal. But when that dimmer switch is broken, your body can’t turn down the inflammatory response and your healthy tissues become damaged.

Autoimmune diseases are an expression of ECS dysfunction.

Medical scientists have discovered that the ECS is dysregulated — meaning that it’s impaired or otherwise not functioning properly — in nearly all disease states, including cancer, diabetes, Alzheimer’s, chronic pain, sleep disorders, and addiction, just to name a few. The health benefits of balancing the ECS are so profound that in 2013, U.S. National Institutes of Health (NIH) scientists Pal Pacher and George Kunos declared that “modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans.”

Given that THC and CBD both modulate the endocannabinoid system, it’s easy to see how medical cannabis is potentially helpful for numerous conditions.


By the late 1990s scientists had mapped out the basics of the endocannabinoid system as we know it today. There are the three chief components of the canonical ECS:

Cannabinoid receptors: These are like miniature portals that sit on the surface of cells throughout our brain, central nervous system, and other organs. They pick up important signals about what’s going on in the body so those cells can take appropriate actions as needed. There are two main types of cannabinoid receptors: CB1 and CB2. Both are scattered throughout your body, but CB1 receptors are concentrated in your brain and central nervous system and CB2 receptors are concentrated in your immune system. Both types of cannabinoid receptors are present in the skin, liver, kidneys, heart, and other internal organs.

Endocannabinoids: These are molecules — our inner cannabis, so to speak — that attach to cannabinoid receptors and activate them like a key turning a lock. Scientists have discovered several more endocannabinoids within our bodies, but two are most prevalent: 2-Arachidonoylglycerol (2AG) and anandamide, named for the Sanskrit word ananda, meaning bliss, because of its reputation as a mood enhancer. These interact with the same receptors as THC and other components of the cannabis plant.

Metabolic enzymes: These enzymes are proteins that accelerate chemical reactions and regulate the levels of our endocannabinoids. They are involved in both creating endocannabinoids when needed and breaking them down and destroying them once the endocannabinoids have served their purpose.


More recently, a fourth component of the ECS was discovered — the transport molecules that act like shuttles for endocannabinoids, ferrying them to where they need to go. Known as fatty acid binding proteins, these transport molecules are also key to how CBD does its job.

When scientists first discovered our endogenous cannabinoids (2AG and anandamide, the ones we create ourselves),they wondered how they made their way through the body’s aqueous interior. After all, blood is mainly water and cannabinoids are fatty lipids — and oil and water are famous for not mixing very well. The key breakthrough came in 2009 with the identification of specific transport molecules for endogenous cannabinoids.

As the name indicates, those fatty acid binding proteins attach to fatty lipids like cannabinoids. In your bloodstream, these fatty acid binding proteins function like a molecular canoe that picks up cannabinoids and shuttles them to where they need to go, including through the cell membrane and inside the cell, where they interact with receptors on the surface of the cell’s nucleus.

Known as peroxisome proliferator-activated receptors, or PPARs, these nuclear receptors regulate gene expression and energy metabolism, as well as other important physiological processes.

CBD, it turns out, is a VIP passenger on those same canoes, and this may have a lot to do with why CBD can have such profound therapeutic effects.

When you take CBD, it’s as if it elbows its way to the front of the cannabinoid line, pushes aside 2AG and anandamide, and takes priority seating on the canoe. That means that your natural cannabinoids hang around on the surface of your cells longer, which gives them more time to activate your CB1 and CB2 receptors, until the next ride comes along to transport your endocannabinoids inside the cell, where they are ultimately deactivated by metabolic enzymes.

In essence, CBD acts a “reuptake inhibitor” that prolongs the natural life cycle of our own natural endocannabinoids so they can confer more therapeutic benefits. Much like you tone weak biceps by lifting weights and exposing your muscle fibers to extra muscle-making stimulus, CBD boosts the “tone” of your endocannabinoid system by exposing it to an extended dose of cannabinoid activity. This may be a key mechanism whereby CBD helps to protect the brain, buffer stress, and fight disease.


Hogging space on those canoes and extending the lifespan of 2AG and anandamide is one way that CBD helps to improve endocannabinoid tone. But that’s not the only way CBD interacts with your endocannabinoid system. In addition to increasing the levels of endocannabinoids by delaying their reuptake and metabolic breakdown, CBD can also alter and adjust how your cannabinoid receptors function.

CBD can elevate the levels of your endogenous cannabinoids and can also finetune the way your cannabinoid receptors function.

THC binds directly to both CB1 and CB2 cannabinoid receptors like a key fitting into a lock and activates these receptors, causing them to send a signal that culminates in a physiological response (less pain, less inflammation, lower blood pressure, mild euphoria, relaxation, etc.). But CBD doesn’t work this way.
Instead of binding with cannabinoid receptors to initiate a signal itself, CBD fine-tunes the signaling that’s been triggered by THC or an endogenous cannabinoid.

Researchers are still trying to figure out exactly how CBD does this, and the science is very much a work in progress, but here’s a glimpse of what we know thus far. Preclinical (in vitro) studies indicate that CBD functions as an allosteric modulator at the CB1 receptor, meaning that it influences how the receptor signals without actually causing it to signal. Think of the CB1 receptor as a dimmer switch or volume control knob — CBD turns it down slightly but not all the way. This appears to be one of the mechanisms whereby CBD lowers the ceiling on THC’s tricky psychoactivity and lessens the high, which is caused by direct CB1 receptor activation.

At the same time, CBD augments CB2 receptor signaling, which regulates inflammation and immune cell activity. How and why CBD triggers an anti-inflammatory response and other CB2-mediated outcomes without directly binding to the CB2 receptor is still somewhat of a scientific mystery. But this much is evident:
CBD can fine-tune the ECS by modulating CB1 and CB2 receptor activity in different directions, tempering the former while amplifying the latter. And this combination can have profound, health-positive effects, particularly for metabolic disorders, obesity, liver disease, and other diseases linked to the Western diet.

To recap: CBD can elevate the levels of your endogenous cannabinoid compounds, anandamide and 2AG, which activate your cannabinoid receptors and cause them to signal. CBD can also finetune the way your cannabinoid receptors function, turning down the volume at CB1 while augmenting CB2 in a manner that balances the body and promotes good health.

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Lower Blood Pressure with Cannabis and WFPB diet

It’s interesting to know that cannabis use can reduce blood pressure. This along with a WFPB (whole food plant based) diet normalizes blood pressure even more.

Cannabis therapy is not my only interest in improving health. Over time, looking to be healthier, Mrs. Weatherstaff and I have weaned ourselves of meat, chicken and fish, not for any particular moral or earth saving reason, mostly just that our tastes have changed.

However, as we move to this more ¨whole food plant based¨ (WFPB) diet, I started to dig a little deeper and find that many modern serious ailments seemed to be caused by a lack of fiber and a high degree of saturated fats and further are cured by a decrease in animal fats in the diet and an increase in fiber by eating mostly fruits, vegetables, all manner of whole grains and legumes.

We searched out the science translated into cookbooks and found these two excellent resources in case that is of interest:

Fiber Fueled Cookbook – Will ´Bulsiewics, MD (2022)
How Not to Die Cookbook – Michael Greger, MD (2017), and possibly the better book

As I am near 75 and had one incidence of cancer, I figure I have nothing to lose by seeing what happens with this change.

In Dr. Greger´s book he points statistically to 14 health risks that are reversed through the WFPB way of eating and to high blood pressure as ¨the number one factor for death and disability worldwide¨

Interestingly, the research on CBD cannabis by Dr. Ethan Russo supports the feedback we have received from two of our clients that taking CBD dominant cannabis extracts have normalized their blood pressure as a byproduct of taking the herbal for other reasons.

Two clients reported about their experience of taking CBD cannabis extract:

Research Scientist: ¨How has my life improved? Good sleep, and far less anxiety, to start with. But nothing short of miraculous, in my opinion, is the impact on my blood pressure which now averages 130/70. I’ve dropped two of three pharmaceutical medications taken for hypertension, and am down to just one.¨

Excavator operator: “My experience has been a bit of a surprise. A good friend recommended I try the 20 mg (CBD rich) capsules to help with sleep and my overall health. I started with a week’s trial and did notice I slept pretty much through the night. There were no side effects that I noticed and I felt pretty good. When I increased the dose to two capsules, the biggest surprise was my blood pressure. I have been dealing with pre hypertension and sometimes hypertension for several years. My blood pressure is now slightly above normal and I’ve had readings below normal as well.”

Well, my thinking is ¨Why not do both? Cannabis therapy and health improve diet and lifestyle?¨

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