CBD and System Inflammation Explained

by Indigo Naturals June 03, 2024

If you dig deep enough, inflammation is hiding in every illness or issue you can think of.

Even aging itself! It's called inflammaging.

This is bad news since we are literally swimming in pro-inflammation toxins everywhere!

A quick intro to inflammation

First…understand the enemy.

Inflammation in itself is a much-needed pathway in the body.

It belongs to the immune system and generally speaks to when the immune system ramps up to address infection, injury, and faulty cells.

That's only half of it! After the battle is done, the immune system then changes to repair/rebuild mode.

Technically, there are two primary settings involved:

TH1 - pro-inflammatory
TH2 - inflammation resolving mode

The issue is when we're stuck in the first one and inflammation never comes down. This leads to collateral damage to our healthy tissue and longer term, just about every disease state you can think of!

Even mental health resides here (see CBD and neuroinflammation).

Interestingly, early stress, trauma, and infection can upregulate the entire inflammation pathway for life! Big review on this process of rewriting your health state.

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Then there's the whole aging thing:

Increased inflammatory markers in older adults are on average 2–4 fold higher than in younger adults.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295067/

This is the whole "inflammaging" change with age:

Inflammaging refers to the age-related increase in systemic chronic inflammatory status. Several contributory factors to inflammaging include accumulated oxidative stress, changes within the inflammatory cytokine network, and cellular senescence with advancing age

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/inflammaging

Oxidative stress is result of our energy production getting messy.
Cytokines are the little assassins called by the immune system to respond to injury/illness and cancer
Senescence is the clean-up process that removes faulty cells - so-called "zombie" cells

Make a note there on those three for CBD's effects below.

Now, let's look at maybe why systemic inflammation is out-of-control aside from aging.

Why is inflammation the issue of the day

We're going to focus on four key drivers that we can actually do something about.

Early stress, trauma, infection can hyperactivate the immune system later in life
Environmental toxins are stimulating inflammation system wide
Steroidal hormones drop as we age
Nutrient and mineral depletion in the soil (and therefore, our food)
Seed oils and Omega 6-3 imbalance

Okay…that's a laundry list (not nearly complete). We have bigger reviews but a few examples for each.

Early stress, trauma, infection can hyperactivate the immune system later in life

Early-life stress predicts later inflammation, and there are striking analogies between the neurobiological correlates of early-life stress and of inflammation.

https://www.nature.com/articles/npp2016198

Huge implications in the brain but it's systemic. More on why the immune system is the future of mental health.

Environmental toxins are stimulating inflammation system wide

We are swimming in toxins. Pesticides, forever-chemicals (PFOA's, etc). Food additives (many are banned in Europe). Endocrine disrupters.

Just a few of unfortunately 1000's of examples.

Glyphosate:

In mammals, including humans, glyphosate mainly has cytotoxic and genotoxic effects, causes inflammation, and affects lymphocyte functions and the interactions between microorganisms and the immune system.

https://pubmed.ncbi.nlm.nih.gov/32897110/

Glyphosate was originally a boiler de-mineralizer. It's main mechanism of killing weeds is by starving them of minerals. The same minerals we need to…detox!

Selenium
Molybdenum
Zinc

All critical in the liver to remove and detox poisons from our body.

PFOA's:

We found that multiple inflammation- and immune-related genes were affected. Taken together, our study demonstrated that PFAS exposure could alter lung biology in a significant manner and may contribute to asthma/airway hyper-responsiveness.

https://pubmed.ncbi.nlm.nih.gov/37239886/

Everyone has this in their blood, unfortunately. Everyone.

Let's move on because we could go and on.

Steroidal hormones drop as we age

Progesterone is a powerful immune calming agent in women.

Unfortunately, it drops by 50% by age 40 and continues down from there.

Learn more about Progesterone and inflammation but testosterone is also a powerful player that's in constant decline from about age 20.

Low testosterone levels are found to be associated with an increased in metabolic risk and systematic inflammation.

https://www.tandfonline.com/doi/full/10.1080/13685538.2018.1482487

Great. Learn about Testosterone's health effects.

Let's turn to nutrients.

Nutrient and mineral depletion in the soil (and therefore, our food)

We're going to focus on minerals here. They are critical to removing toxins and if the liver can't keep up, inflammation is going to rise.

Especially if the gut barrier starts to get weakened and bacteria are able to escape into the body. Check out CBD and autoimmune or CBD and dementia to see the repercussions from this.

Magnesium is a monster here:

Subclinical magnesium deficiency caused by low dietary intake often occurring in the population is a predisposing factor for chronic inflammatory stress that is conducive for chronic disease.

https://www.tandfonline.com/doi/full/10.1080/13685538.2018.1482487

Same goes for zinc, selenium, and molybdenum.

Of course, your B vitamins, Vitamin D, and other key nutrients are key to immune function.

Big reviews on magnesium, B vitamins, and Vitamin D.

One more stop…

Seed oils and Omega 6-3 imbalance

The type of fat really matters and our diet is just drowning in seed oils (canola, soy, sunflower, etc). Big review on the Fats issue but here's the take-away.

This skews the Omega 6 ratio to Omega 3 much higher with this effect:

Omega-3 fatty acids help reduce inflammation, and some omega-6 fatty acids tend to promote inflammation. In fact, some studies suggest that elevated intakes of omega-6 fatty acids may play a role in complex regional pain syndrome.

https://www.mountsinai.org/health-library/supplement/omega-6-fatty-acids

Lots more at the Fats review.

Okay…that's just a teaser. Sorry…our modern world is highly inflammatory. Try grounding, reduce seed oils, get lots of NIR exposure, balance real food without seed oils.

Let's turn to one potential tool.

Does CBD help with systemic inflammation?

First, we need to understand where CBD works.

The endocannabinoid system.

A system we all have which is tasked with balancing other key systems including:

Nervous system
Endocrine system (hormones)
Immune system (ding ding ding!!)

The key word there is "balancing" or the technical term, homeostasis.

Remember…the immune system is supposed to respond strongly to infection or injury and then come back to…balance.

The issue with other cannabinoids like THC is that it works in one direction. In fact, THC is a big immune suppressor but it hits too hard and for too long compared to the natural chemical it mimics…anandamide.

For this reason, THC builds tolerance longer term. The body actually pushes back.

CBD doesn't build tolerance. It actually works like a feedback mechanism.

Technically called an allosteric modulator.

Its effect on cancer (which is managed by inflammation both in terms of cause and removal) is very telling.

Healthy cell with low inflammation - CBD has no effect
Healthy cell with high inflammation - CBD reduces inflammation
Cancerous or virally-infected cell - CBD INCREASES inflammation

The last example make sense once you understand that the body's natural way to combat cancer is by jacking up oxidative stress to kill off faulty cells.

Three different effects from CBD isolate depending on three different states.

What about low level, general inflammation across the body.

We see this increase as we get older and it's termed "inflammaging".

In fact, the increase in cholesterol may actually reflect a general inflammation state since cholesterol has a very important role of sticking to bacteria and intruders to disarm them.

Go figure!

Let's dig into the components and studies around CBD and inflammation.

First, the inflammatory assassins called cytokines.

Look at its effects on the little assassins of inflammation, called cytokines:

The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458548/

What's the deal with IL-10? Remember how people who didn't have enough IL10 would see gut inflammation continue to a disease state?

IL10 just happens to be anti-inflammatory! Key to "resolving" inflammation.

CBD actually increases it!

What about when systemic inflammation hits the gas pedal. The so-called cytokine storm that can do more damage than what the immune system is actually responding to.

Just one study for lung inflammation (sound relevant??):

In a lung inflamed mouse model, we observed a reduction in leukocytes including neutrophil migration to the lungs and decreased levels of IL-1β, MCP-1, IL-6 and TNFα, in response to the administration of the high-CBD extract.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149302/

So…a reduction of key inflammatory agents. TNFa is a major player as is IL-6 (big in autoimmune).

We looked deeply at CBD and mast cell activation syndrome. Mast cells are key reservoirs of histamine (allergic reaction driver) and inflammatory agents.

Big review of CBD and histamine but we would expect CBD to calm this response if it has an effect on systemic inflammation.

The fascinating piece is that CBD supports the backend…the system in charge of calming the inflammatory response.

The key players with mast cells are called MDSC or Myeloid-derived suppressor cells. They are the "ramp down" for this forward guard of inflammation in the body.

In cases where our inflammation is over-reacting (MCAS), what does CBD have to do with this interaction?

Together, the results suggest that CBD may induce activation of PPARγ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433789/

So…CBD supports the calming system via MDSC!

We can also look all over the auto-immune landscape which is a type of systemic inflammation.

We have a big review on CBD and autoimmune but a summary level look:

These findings demonstrate the beneficial effect of CBD treatment on autoimmune neuroinflammation by ablating expression of pro-inflammatory chemoattractants, regulating inflammatory macrophage activity, promoting MDSC expansion, and limiting the systemic low-grade inflammation in the GI tract, culminating in the attenuation of EAE.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10207886/

Goodness.

Reduction of inflammatory agents
Boosting MDSC (calms inflammation)

Did you catch the last one…

"Limiting the systemic low-grade inflammation"

Isn't this exactly what we're looking for and in the gut of all places.

All inflammation starts in the gut!

It's this low-grade systemic inflammation that's at the heart of chronic illness of both body and brain (see CBD and brain inflammation).

Speaking of the brain?

EVERY mental health issue shows signs of systemic inflammation.

The microglia are the brain's immune sentinels that can become hyperactivated and cause tremendous damage.

CBD's effect there such as with Alzheimer's?

In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD. Given that CBD lacks psychoactivity, it may represent a novel therapeutic approach for this neurological disease.

https://www.researchgate.net/publication/50196075_Cannabidiol_and_Other_Cannabinoids_Reduce_Microglial_Activation_In_Vitro_and_In_Vivo_Relevance_to_Alzheimer's_Disease

Many more studies on CBD and neuroinflammation.

The net net…

Clinical studies are now warranted to establish the therapeutic role of CBD in diseases with a strong inflammatory component, such as multiple sclerosis and other autoimmune diseases, cancer, asthma, and cardiovascular diseases.

https://pubmed.ncbi.nlm.nih.gov/36834537/

The interesting piece there is cancer is actually requires a more robust inflammatory response.

We don't want to just repress inflammation across the board. It has a very important role in the body. Part of which is keeping cancer at bay not to mention infection!

Let's get to practical questions.

How much CBD for system inflammation

Two ways to look at this.

For more serious inflammatory states, you can go higher to start and then bring it down over time.

600-800 mg is for more serious issues
300 is peak neurogenesis (also an aspect of the immune system but on the repair sign)

Once there is stability, people generally go down to 100mg or lower.

Hold it under your tongue up to 60 seconds to boost availability (and save money!!!)

Check with your doctor regarding medications you take as most use the same liver pathway for processing as CBD.

So…start stronger and scale down. Combine with magnesium glycinate (or citrate) and check out our MCAS toolkit since it's the canary in the inflammatory coal mine.

The kind of CBD really matters for systemic inflammation?

What's the best CBD for inflammation

First, the are basic requirements:

Organically grown hemp in the USA at FDA registered farms
3rd party tested
CO2 cold-processed
No pesticides
No heavy metals
No solvents
No mold
No bacteria

This must all be 3rd party tested since there's so much back product out there.

Our testing is here.

Next us, all the research above is on CBD isolate. CBD by itself.

The issue with THC is that longer term, it's an immune suppressant. That's the wrong direction.

Other cannabinoids can have similar effects.

We can use histamine as our litmus test. If full or broad spectrum causes a histamine response (very common at about 40-60% of the population), then that's more systemic inflammation.

Big review on CBD isolate for histamine but it actually calms this response (a good indicator).

Just look at our review for people with CBD isolate versus full spectrum. It can be night or day and that's how we found CBD isolate to begin with.

4-5 of the biggest CBD brands make us feel terrible. Gut issues. Inflammatory responses.

One final note. We looked at how many of our modern diseases may actually point to endocannabinoid deficiency. It's just overrun.

Tons of NIH studies going deep into what's going on!