Updated Research on CBD and the Pathways of Autoimmune Disease

Turn on any TV show (that has commercials) and you're likely to see an ad for autoimmune medications.

Now...as the person on screen is building a paper mache fence for their daughter's play (or some other creepily wholesome scene), pay attention to the side effects.

Some scary stuff.

Every other ad.

The reason for this is a perfect storm of events...an explosion in diagnosis as well as price tags for the various meds.

Some of these medications can run 10's of thousands of dollars per year.

As for the rise, look at the annual increases found in UK research:

• 7.0% increase per year of rheumatic diseases such as rheumatoid arthritis
• 6.3% increase of endocrinological conditions such as type 1 diabetes
• 3.7% increase of neurological such as MS
• Coeliac disease shows the greatest increase per year at about 4–9% a year

https://www.immunology.org/news/report-reveals-the-rising-rates-autoimmune-conditions

The last one is telling and we'll get into the role of the gut and microbiome for autoimmune.

Newer research is really pointing to the gut barrier as a key player.

We'll go there as well as genes, Vitamin D, and a host of clues in research.

Finally, we'll turn our attention to CBD which is shown to have a powerful effect on immune hyperactivation.

Along the way, we'll touch base on other tools which come out of research (NAC, berberine, etc).

Here are the general areas:

• A quick intro to what is happening with autoimmune
• The first straw to drop...our gut barrier and microbiome
• Risks tied to autoimmune diseases
• Clues to the "bacteria on the loose" theory explanation
• Immune hyperactivity and autoimmune
• The curious connection with Vitamin D (maybe most important) and autoimmune
• Can CBD help with autoimmune
• How much CBD to take for autoimmune diseases
• What's the best CBD for autoimmune

Let's get started.

A quick intro to what is happening with autoimmune

We all have a pretty good understanding that the immune system is attacking our own tissue.

It's "misreading" our cells as being foreign entities and one of its primary functions is to destroy such wayward travellers.

Or is it?

Newer research is pointing to a more obvious explanation of how this misreading might get started!

Bacteria and outside entities are indeed gaining access to our body and the immune system is responding when and where it finds them.

This is war and there's always collateral damage (our cells!).

There are now so many clues to this basic mechanism!

When researchers looked at the DNA for arterial plaques, they found the signature of bacteria!

Bacteria gained access and the immune response encased them in prisons along our arterial lining. Cholesterol is just the spackle!

You need inflammation (the immune system's main weapon) to seal the deal.

Look at what happens when antibiotics are used in terms of autoimmune diseases:

The researchers also found that the autoimmune reaction can be suppressed with an antibiotic or vaccine designed to target the bacteria, they said.

https://www.sciencedaily.com/releases/2018/03/180308143102.htm

This makes no sense unless the antibiotics are reducing the bacteria load and the immune system is able to finally stand down.

Scientist can even trigger autoimmune responses by introducing bacteria to mice who are genetically susceptible:

the researchers observed that in tissues outside the gut, E. gallinarum initiated the production of auto-antibodies and inflammation -- hallmarks of the autoimmune response.

https://www.sciencedaily.com/releases/2018/03/180308143102.htm

What about dementia?

It turns out that amyloid beta, the building block of the plaques that are the signature of the disease are actually little bacteria killers!

Check out CBD and dementia here.

Again, we can go on and on with such research.

The research on strep infection and psoriasis or gluten and Hashimoto's (thyroid disease) are just two specific examples we dove deep into where a protein in the attacker looks just like one in a specific tissue (skin and thyroid in our examples).

Let's turn our attention now to the weakest link in our protection from the outside world.

The first straw to drop...our gut barrier and microbiome

There are only so many "surfaces" to the bacterial world.

• Skin
• Ears, nose, and throat
• Gut
• Genitals

The gut is by far the most susceptible in today's modern world.

Bacteria and host of different living and partially living (viruses) things hitchhike a ride with our food.

Our world is surrounded by them and estimates say that bacteria outnumber our cells by 10,000 to 1!

The gut barrier has to allow in vital nutrients in but keep out interloping bacteria.

It's a very complicated system involving other "good" bacteria, a tight, interlocking lining, and immune cells.

What happens if these various protections get weakened and what do such a thing?

Turns out a lot of our modern world does this very thing:

• Chemicals
• Pesticides (after all, the "good" bacteria are the targets as well)
• Drugs and medications
• Highly processed foods including fake sugars and fats

Learn all about the gut barrier at our CBD and gut barrier or CBD and microbiome reviews.

So...is there a connection with autoimmune diseases to back our premise above?

Yes!

Increasing evidence in recent years suggests that microbial translocation and intestinal barrier dysfunction, which may be affected by gut microbiota, are another important causative element for autoimmune disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/

Across the gamut of autoimmune which paints a picture of a similar process that displays according to where the immune system attacks.

Does leaky gut come first or as a result of autoimmune disease progression?

Look at Type 1 diabetes for clues:

First, studies utilizing human subjects affected by T1D or T1D-prone animal models have indicated that impaired intestinal barrier function occurs before disease onset

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/

"Before disease onset".

When the correct the gut barrier issue in rats, the disease reverses:

Reversion of intestinal barrier dysbiosis by adding a zonulin inhibitor ameliorated T1D manifestations in disease-prone rats

This is Type 1 diabetes, the kind you're born with. "Reverses" is not a typical procession.

As for the antibiotic connection above?

Mice spontaneously develop lupus when TLR4 responsiveness is increased, whereas the exacerbated disease phenotype can be significantly ameliorated when the commensal gut flora is removed by antibiotic treatment

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/

To translate...in lupus, TLR4 is our immune response to bacteria and when it calms down by removing the bad bacteria IN THE GUT, the disease calms down.

You can pick any autoimmune disease and find the same pattern.

Rheumatoid arthritis?

In murine models, the parenteral injection of cell wall fragments from various intestinal bacteria is arthritogenic [17] and in this model, arthritis is not developed when bred in germ-free conditions; otherwise, it is presented when intestinal bacterial species are introduced

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602494/

Let's translate that because it is really important.

In mice models for RA, they will inject certain bacteria which leads to arthritic conditions. The same mice, when bred without exposure to bacteria (germ free), do not develop arthritis.

The deciding factor was introduction to specific species of bacteria in the gut.

Again, the actual bacteria (our first layer of protection for the barrier - a living layer!) is crucial.

Look at MS:

Studies show the MS gut microbiome as having general alterations in specific taxa, some associated with the promotion of inflammatory cytokines and overall inflammation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163724/

Again, pick your poison (autoimmune disease) and find the connection.

So...some people can eat lots of processed food and never get autoimmune diseases.

Why?

Let's look at the risk profile and see how it fits into the above situation.

Risks tied to autoimmune diseases

There are key drivers of risk for autoimmune:

• Genetics - genes tied to immune response are front and center!
• Gender - women are hit with 80% of diagnosis (progesterone calms immune response and it's fleeing the scene - down 50% by age 40)
• Obesity - fat is a known cause of inflammation (see our fats review)
• Medications - statins and other blood pressure meds can be a risk factor
• Alcohol and Drugs - both can damage gut barriers

Let's look at the medications to see if it fits the profile above.

First, statins:

Atorvastatin and rosuvastatin significantly increased the abundance of the genera Bacteroides, Butyricimonas, and Mucispirillum. Moreover, the abundance of these genera was correlated with the inflammatory response, including levels of IL-1β and TGFβ1 in the ileum.

https://www.frontiersin.org/articles/10.3389/fmicb.2019.01947/full

Inflammatory response. The first shoe to drop. That means the immune system is picking up steam...chronically. That's statins!

What about the blood pressure meds?

The results showed that the genes relating to a specific type of calcium channel blocker — called the “nondihydropyridine class” — may increase the risk of a bowel condition called diverticulosis.

https://www.medicalnewstoday.com/articles/325722#Calcium-channel-blockers-and-diverticulitis

What about gender? Why are women hit so hard?

Sex hormones, such as estrogen, testosterone, and progesterone, are believed to mediate many of the sex-based differences in the immune response and to account for sex differences in the prevalence of autoimmune diseases

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527069/

Don't get us started...it was perimenopause and a loss of hormones that led us to find CBD to begin with!

Our money is on progesterone since it's general effect is to calm or modulate immune response.

See Progesterone and the immune system or estradiol review here.

By the way, VItamin D is essentially for maintaining the gut barrier and roughly half of the US population is deficient (up to 80% for African Americans). See Vitamin D review...maybe most important work we've done!

Let's turn our attention to the wayward bacteria escaping into the body.

Clues to the "bacteria on the loose" theory explanation

Can we actually see examples of this great escape in our bodies?

First, there was the Yale study which designed a study to specifically target one type of bacteria:

Bacteria found in the small intestines of mice and humans can travel to other organs and trigger an autoimmune response, according to a new Yale study.

https://news.yale.edu/2018/03/08/enemy-within-gut-bacteria-drive-autoimmune-disease

When they delivered an antibiotic targeted to this bacteria (in muscle tissue to avoid other gut bacteria), the autoimmune response came down.

This is close to a smoking gun!

There's a great review of it here with the caption:

Gut microbe drives autoimmunity

https://www.nih.gov/news-events/nih-research-matters/gut-microbe-drives-autoimmunity

Another theory gaining steam is that fragments of bacteria can resemble actual human proteins and the immune system may start to target our cells accordingly.

It's called protein mimicry.

A group of researchers were able to find such a bacteria in people with lupus:

Kriegel and his colleagues demonstrated a molecular mimicry response in cells from people with lupus using a bacterial protein very similar to the human protein Ro60

https://www.nature.com/articles/d41586-020-00197-z

Interestingly, scientist are finding traces of bacteria in places they shouldn't be and ones reflecting autoimmune disease.

For example:

Steere and his colleagues found evidence of Prevotella DNA in the joints of some people with rheumatoid arthritis

https://www.nature.com/articles/d41586-020-00197-z

What is bacteria DNA doing in joints of people with arthritis?

Then there's the plaques of arterial sclerosis:

The applied approach enabled the detection of bacterial DNA in all atherosclerotic plaques.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063344/

This was groundbreaking research back in 2014-2016. Is arterial sclerosis just another autoimmune disease?

Bacteria breaking through the gut barrier (or mouth...hence tie between gum disease and heart disease??) and gains entry to our body (and brain - see CBD and the brain barrier). Then what?

Immune hyperactivity and autoimmune

This is where genetics comes into play.

Most of the genes tied to autoimmune risk (aside from gender-related hormones) are squarely in the immune response system.

Research conducted by Gomez et al. [68] provided the first demonstration that HLA genes and intestinal environment interact to affect the susceptibility of arthritis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602494/

HLA stands for human leukocyte antigen, a small piece of a very complex system that adapts our immune system to new threats we haven't seen before.

The production of antibodies, a hallmark of autoimmune disease.

When the immune system finds stray bacteria, it responds as its supposed to.

Inflammation! Cytokines, the little assassins of our immune response are called into action.

Do we see this with autoimmune diseases?

increasing evidences have shown that the abnormal inflammatory response is closely associated with many chronic diseases, especially in autoimmune diseases, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), gout, and diabetes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421792/

And yes, this inflammation is present in the gut (maybe first!).

Newer research is pointing to chronic inflammation as a key component.

The inflammatory response is supposed to ramp to address a threat (infection, etc) and the "resolve" or calm down.

If there's a constant flow of bacteria across a damaged gut barrier, the immune system is left turned "on".

This is where the genetics figures in such as this piece of the puzzle:

“We’ve found that chronic inflammation and autoinflammatory disorders can originate from genetic mutations to MDA5 that cause it to misrecognize ‘self’ as ‘non-self,’ essentially launching the immune system into self-attack mode,”

https://vector.childrenshospital.org/2018/02/mda5-autoinflammatory-disease/

Again, inflammation can occur in the gut and signal to the immune system for the rest of the body but remember how they found provella DNA signatures in joints of people with arthritis?

Look at this:

Species that colonize the human gut, such as Prevotella copri, Ruminococcus gnavus, and Lactobacillus salivarius, are implicated in the pathogenesis of AIDs.

https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(20)30103-9

Again, back to the gut.

As for the inflammatory agents themselves (cytokines), do we see increases there?

Taken together, the inflammatory circuit of TNFα, IL-6, IL-23 and IL-17 plays a critical role in host defense and tissue repair, whereas the dysregulation of this inflammatory circuit leads to the development of autoimmune diseases such as psoriasis.

https://academic.oup.com/intimm/article/28/4/181/2614115

We'll come back to those in our CBD section below. Check out CBD and neuroinflammation for more info.

Let's first turn a critical piece of the gut barrier puzzle.

The curious connection with Vitamin D (maybe most important) and autoimmune

We did a major review of Vitamin D and were astonished at just powerful it was for autoimmune diseases especially considering the high rate of deficiency.

Here's the important piece:

Vitamin D deficiency (low serum levels of 25(OH)D) is prevalent in multiple autoimmune diseases, e.g. MS, TIDM, and SLE.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047889/

Look at this:

Women who had a higher intake of dietary vitamin D (approximately 700 IU/day) had a 33% lower incidence of MS compared with those with lower intake. In addition, women who used vitamin D supplements (≥ 400 IU/day) had a 41% reduced risk of developing MS compared to non-users.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990512/

Keep in mind that the endocrinologist have much higher required levels than the standard nutrition guidelines:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990512/table/Tab1/

This is so common in the US (throughout the World really).

Obesity is a huge factor with Vitamin D deficiency which may be the tie to autoimmune.

More importantly, look at D's connection to the gut barrier.

Vitamin D (VD) has been recognized as an intestinal permeability protector by inducing the expression of TJ proteins ZO-1 and claudin-1.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/

TJ stands for "Tight Junctions", the wall that keeps bacteria out of our bodies.

D literally supports the integrity of our gut barrier (and brain barrier).

More importantly, the RDA is out of date with what research and endocrinologist are saying (70-80 nmol/l levels for protection).

Read the review. I have a VDR gene variant where I don't process D well. I'm taking 10,000IU and barely moving the dial with 30 minutes of sun a day.

Get your D tested and see where you're at. Very important.

Also, for gut barrier protection, look at berberine and turmeric. We have a full review on berberine.

Let's finally turn to CBD!

Can CBD help with autoimmune pathways

We'll break it down according to the areas we discussed above before diving into the studies on CBD directly.

• CBD and the gut barrier
• CBD and the immune response - hyperactivation
• CBD and inflammation
• CBD and autoimmune research

Let's get started!

CBD and the gut barrier

We have to start in the gut!

This may be the first shoe to drop with autoimmune long before our immune system overreacts.

What about CBD there?

A study looked at CBD's effect to gut lining cells after exposure to C diff bacteria, an especially destructive class of pathogen:

Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721977/

C diff is very fascinating clue in this puzzle for autoimmune.

Researchers see infection by C diff followed by colitis (inflammatory disease of the colon) and then...arthritis!!

The hypothesized pathogenesis of reactive arthritis following an enteric infection with C difficile is postulated to be an autoimmune response to bacterial antigens in joints and other tissues that gain access into the bloodstream via the intestinal mucosa

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881974/

Other studies found similar connections with lupus.

From the study above, CBD reversed the negative impacts on barrier cells following C diff exposure.

This alone is pretty fascinating.

Another study looked at heavy metal poisoning essentially on gut barrier cells and CBD:

CBD prevented EDTA- and cytokine-induced increased paracellular permeability in the Caco-2 cell culture model and increased the expression of the tight-junction protein zonula occludens 1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333598/

This is equally important. Remember how much of the rise in autoimmune is accredited to environmental factors?

Chemicals. Medications. Drugs. Etc.

These have all been shown to erode our gut barrier especially when ingested.

EDTA is a chemical that holds on to heavy metals.

There are other tools that support gut barrier as well:

• Berberine - thickens the mucus of the gut lining - see the review
• PEA - a fascinating support of the gut
• Turmeric - powerful antiinflammatory effects

Let's turn to the immune system and CBD.

CBD and the immune response - hyperactivation

We covered this in detail in terms of the brain at our CBD and neuroinflammation section.

This has big impacts for mental health (see CBD and mental health) which by the way, is deeply connected with autoimmune.

It's all one big system after all!

A very complicated system at that.

We won't dive too deep into the weeds here as immune response quickly follows down the rabbit hole.

From a 30,000 foot view, let's start with the general "setting" of immune response.

There are two basic settings...Th1 and Th2.

In general, Th1 is more aggressive and proinflammatory. It is generally triggered by increased need to fight bacteria and pathogens.

The connection with autoimmune is clear:

Th1-type cytokines tend to produce the proinflammatory responses responsible for killing intracellular parasites and for perpetuating autoimmune responses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27457/

A study looked at CBD's effect on non-diabetic mice. First, the initial statement:

We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice.

https://pubmed.ncbi.nlm.nih.gov/16698671/

Deeper down in the study was this piece:

Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice.

CBD shifted the immune response from Th1 to Th2!

We had a huge review of CBD and immune response but during the pandemic period, we had to take it down.

You also see the cytokines...messengers of inflammation mentioned. Let's go there now!

CBD and inflammation

Let's zero into the cytokines mentioned above.

Remember from above that there's a direct tie between autoimmune diseases and specific cytokines?

" TNFα, IL-6, IL-23 and IL-17"

Those are all pro-inflammatory cytokines.

What about CBD's effect on cytokines...the messengers of inflammation?

In study of asthma (classic autoimmune with histamine lever), the following results were found:

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 gives with IL-10?

Just this...it's an antiinflammatory cytokine used by the immune system to "resolve" or calm immune response!

Then there's the other type of inflammation...oxidative stress.

WE have entire system to keep this at bay since it's so destructive (see CBD and glutathione or CBD and oxidative stress).

CBD is actually a more potent absorber of free radicals than Vitamin C and E, two superstars of antioxidant work (C directly supports recycling of glutathione)!

CBD exhibits much more antioxidant activity (30–50%) than α-tocopherol or vitamin C

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/

Let's finally turn to research on CBD and autoimmune directly.

CBD and autoimmune research

We'll first jump into studies on specific illness.

Let's start with the most prevalent in this order:

• CBD and rheumatoid arthritis
• CBD and colitis or Chrohn's disease
• CBD and type 1 diabetes
• CBD and lupus
• CBD and psoriasiss
• CBD and MS
• CBD and thyroiditis

We can then touch on other specific research.

CBD and rheumatoid arthritis

First, mice were basically induced to get rheumatoid arthritis and then tested with CBD to see the effects:

Ex vivo, draining lymph node cells from CBD-treated mice showed a diminished CII-specific proliferation and IFN-γ production, as well as a decreased release of tumor necrosis factor by knee synovial cells.

https://pubmed.ncbi.nlm.nih.gov/10920191/

Let's decipher that.

The mice treated with CBD had lower levels of the inflammatory agents (IFN-y) and the cell growth agents that drive the pain in the joints. TNF is another inflammatory agent directly tied to rheumatoid arthritis.

This and other effects led the researchers to state:

Taken together, these data show that CBD, through its combined immunosuppressive and anti-inflammatory actions, has a potent anti-arthritic effect in CIA.

CIA is collagen induced arthritis - rheumatoid arthritis by another name (in mice).

One of the hallmarks of rheumatoid arthritis is pain and swelling.

Another animal study:

Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration and thickening of the synovial membrane in a dose-dependent manner.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/

A newer study looked at a synthetic version of CBD for people with the following effects:

In comparison with placebo, the CBM produced statistically significant improvements in pain on movement, pain at rest, quality of sleep, DAS28 and the SF-MPQ pain at present component.

https://pubmed.ncbi.nlm.nih.gov/16282192/

Synthetic CBD is not as good as pure CBD isolate as evident by the vastly different side effect profiles.

We look forward to full trials with CBD isolate but expect more of the same considering the pathways mentioned above.

Make sure to check out vitamin D review!

Let's turn to the gut...where autoimmune probably starts.

CBD and Colitis, Irritable Bowel Syndrome, or Chrohn's disease

Inflammatory diseases of the gut are becoming much more common.

First understand that our natural endocannabinoids are intricately involved in the inflammatory state of our digestive tract.

We'll start with the animal studies first.

Plant cannabinoids THC and CBD proved beneficial in DNBS-induced colitis in a bell-shaped dose-related response

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038810/

DNBS is a nasty chemical that essentially leads to the colitis disease.

One note...CBD is very different than THC. The issue with THC is that it builds tolerance longer term which means we're going the wrong direction!

This may get technical but we'll decode after (promise):

Finally, MAGL and FAAH blockade, as well as blockade of atypical cannabinoid receptor TRPV157, are important to attenuation of colitis, and studies demonstrate a close link of these endocannabinoid hydrolases to CB receptors in the ECS

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038810/

FAAH is very fascinating. It breaks down our main endocannabinoid, anandamide (named after the Hindu goddess of bliss).

CBD blocks FAAH in a feedback way, which is beneficial for colitis.

That study gives some guidance on dosage at 10 mg/kg...our about 600mg for a 160 pound person.

Another study looked at the effects on colitis patients with the following effects:

CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients.

https://pubmed.ncbi.nlm.nih.gov/22163000/

Let's get to the heart of the issue.

How does CBD affect our immune response to LPS, bacteria signatures?

A study in an lipopolysaccharide-induced model suggested that CBD, which is known to act as GPR55 antagonist [46], inhibits GI inflammation by controlling the inflammatory response and the activation of enteric glial cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388177/

We have to translate this because it's too important.

CBD stimulates a specific pathway called GPR55 (see CBD and GPR55 for anxiety).

This pathway is critical to our inflammatory state in the gut.

Glial cells are the immune commanders in our nervous system...and yes, the gut has an intricate nervous system...the most neurons outside of the brain!

The net net effect is this...reduced GI inflammation!

GI inflammation is literally the disease with IBD (irritable bowel disease), colitis, and Chrohn's!

Or at least the calling card. Big review on CBD and IBD.

For the gut specifically and autoimmune in general, research the following to protect the gut and microbiome environment:

• Berberine (or metformin) - both thicken the mucus that protects the gut
• PEA - powerful antiinflammatory effects in the cannabinoid family
• NAC - reduces oxidative stress
• Vitamin D- literally responsible for keeping up our gut lining!
• Turmeric - all around, general antinflammatory

Again, this pertains to all autoimmune!

What about diabetes?

CBD and type 1 diabetes

Remember the study on mice and diabetes from above:

We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice.

https://pubmed.ncbi.nlm.nih.gov/16698671/

NOD is important since it's a correlation to Type 1 (non-obese diabetes).

What about Type 1 diabetes?

Clearly, the early form of diabetes (as opposed to adult-onset) isn't tied to the gut, right?

Well…

Altered composition of gut microbiota is associated with decreased SCFA production and increased IgAbinding in T1D patients

https://diabetesresearchconnection.org/wp-content/uploads/Final-report-Hu.pdf

They went on to say…

We found increased α-diversity (Figure 1B and 1C), with a significant increase in the relative abundances of Ruminococcaceae and Coprococcus (Firmicutes) at the species level in individuals with T1D, compared to control subjects

Could these families of bacteria have pieces that resemble islet cells (which are attached by our immune system in diabetes Type 1)?

More interesting to us is the effect of early life stress, trauma, or infection across all autoimmune:

We would look for other clues.

C-sections (since the gut flora isn't able to pass down to child during vaginal delivery).

Ummm….

A recent meta-analysis of 20 studies worldwide reported that C-sections, independent of maternal age, birth weight, and breastfeeding, contributed a 20% increase in the risk of T1D

https://diabetes.diabetesjournals.org/content/61/1/36

Interestingly, both C-sections and Type1 diabetes have exploded higher 50% since the 90's.

What about antibiotics?

Young children who take a single course of antibiotics could be at an increased risk of developing type 1 diabetes, researchers have said.

https://www.diabetes.co.uk/news/2018/jul/antibiotics-early-in-childhood-could-increase-risk-of-type-1-diabetes-97995417.html

Okay...we could investigate this for pages on end but what about CBD?

Looking at some of the key signatures (or results) of type 1 diabetes, CBD does the following:

CBD-treated NOD mice developed T1D later and showed significantly reduced leukocyte activation and increased FCD in the pancreatic microcirculation.

https://pubmed.ncbi.nlm.nih.gov/27767974/

This is calming the progression of the disease.

Leukocyte are the "L" in IL from above. They're in charge of fighting "foreign" entities like incorrectly labeled islets cells in the pancreas.

FCD is functional capillary density...a signal of health and function in the pancreas (the opposite of atrophy and loss).

What about once Diabetes is already in effect?

There's a litany of downstream effects on so many different pathways from the dysfunction of Type 1 diabetes.

This study was specificallly looking at CBD's effect in the brain from diabetes:

Repeated CBD treatment decreased body weight in both sham- and CCH-operated animals. Cannabidiol improved memory performance and reduced hippocampal levels of inflammation markers (inducible nitric oxide synthase, ionized calcium-binding adapter molecule 1, glial fibrillary acidic protein, and arginase

https://pubmed.ncbi.nlm.nih.gov/30430393/

Like we said, a laundry list since insulin and sugar management is such a critical pathway for every other system.

Basically, a big reduction in the brain inflammation that flows from diabetes.

Our favorite data point was CBD's effect on BDNF, which is our brain's fertilizer. Check out CBD and neurogenesis or CBD and BDNF to learn why this is so important from brain health and mental health.

Let's turn our attention to lupus.

CBD and lupus

Interesting new research is pointing to dysregulation of our natural endocannabinoid system and lupus.

Liquid chromatography-mass spectrometry quantitation of eCB levels highlighted that plasma levels of 2-arachidonoylglycerol (2-AG) were significantly increased in SLE patients compared to HS

https://pubmed.ncbi.nlm.nih.gov/29655919/

2-AG is one of our major cannabinoids (alongside anandamide from above - our "bliss" molecule).

Lupus is interesting in that it displays in many areas of body including organs.

It's a characterized by a massive state of inflammation system-wide.

Here's where it gets interesting for lupus specifically.

Recent studies have found that a gene, FAAH, is upregulated in people with Lupus (SLE).

FAAH is fascinating! We wrote about it in our review of the woman who can't feel pain, anxiety, or depression.

It breaks down our two main endocannabinoids, 2-AG and anandamide.

People with Lupus are breaking these down two quickly and look what happens when researchers block FAAH activity:

Pharmacological inhibition of FAAH reversed the increase in receptor revision, RAG expression, and polyreactive autoantibodies in lupus-prone mice.

https://pubmed.ncbi.nlm.nih.gov/26773143/

Let's translate please.

Basically, when they block FAAH activity, certain hallmarks of lupus progression (immune cell activation and antibody production to our own immune cells) reversed!

Anandamide and 2-AG are known to have powerful immune suppressing and management duties.

So...what does that have to do with CBD?

It was found that CBD inhibits both AEA hydrolysis by FAAH-containing membrane preparations (Watanabe et al., 1996), and AEA uptake by RBL – 2H3 cells via the AMT

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573017/

CBD blocks FAAH which leaves more anandamide (and 2-AG) available!

We look forward to studies on CBD and lupus specifically.

PEA (Palmitoylethanolamide ) is another interesting tool to look at.

Let's move to the skin.

CBD and psoriasis

A quick lay of the land is in order. Deep dive on CBD and psoriasis here.

Psoriasis is the result of a mismatched growth/death cycle of skin tissue resulting from our immune system (T cells specifically) attacking it.

Part of this process is an increase of keratin (the substance that gives all our tissue varying levels of hardness) in our skin.

Hence, the scaly and thickened layer of skin.

Let's start there with CBD.

Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.

https://www.ncbi.nlm.nih.gov/pubmed/17157480

What about the excess skin growth?

Remember that the immune system governs cell birth and death (called apoptosis) and the endocannabinoid system governs the immune system!

As for CBD:

These findings show that the phytocannabinoids cannabidiol and cannabigerol are transcriptional repressors that can control cell proliferation and differentiation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791996/

This is part of CBD's effect on cancer.

In fact, cancer also speaks to one of CBD's greatest tricks.

It's called an adaptogenic which means it can have different effects depending on the state of the system.

For example:

• Healthy cell with low inflammation - CBD has little effect
• Healthy cell with high inflammation - CBD decreases inflammation
• Cancerous or virally infected cell - CBD INCREASES inflammation

Why on Earth would it do that in the 3rd example?

Inflammation (in the form of oxidative stress) is how the immune system kills of awry cells.

That's essentially what chemo and radiation treatment cause...massive amounts of oxidative stress.

Look at how this applies with psoriasis:

We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.

https://pubmed.ncbi.nlm.nih.gov/32121131/

Okay...this is utterly fascinating.

In healthy skin cells...no effect or calming effect. In skin cells that are marked with too much keratin (hard, scaly result - psoriasis), CBD kills off the cells that make keratin (resulting in less hardness, scaling, etc).

This is part of the natural balance between cell birth/death that's out of whack with psoriasis.

A study looked at CBD's effect on a variety of skin issues including psoriasis (and scarring):

Based on skin evaluations (hydration, TEWL, elasticity), clinical questionnaires (SCORAD, ADI, PASI), and supported by photographic data and investigators' clinical assessment, the results showed that topical treatment with CBD-enriched ointment significantly improved the skin parameters, the symptoms and also the PASI index score.

https://pubmed.ncbi.nlm.nih.gov/30993303/

CBD appears to calm the immune response down which underlies psoriasis (and every autoimmune disease for that matter):

The beneficial effects of phytocannabinoids THC and CBD in psoriasis are the conversion of the pro-inflammatory Th1 profile to an anti-inflammatory Th2 type expression, and the anti-proliferative properties on keratinocytes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037408/

THC has issues in terms of normalization and other aspects. See CBD versus THC here to learn more.

Let's turn to MS.

CBD and MS

Multiple Sclerosis is a horrible autoimmune disease where our immune system attacks the lining of our nerves. Deep dive on CBD and MS.

Some of the original research was based on cannabis itself with THC and CBD being the two biggest factors there.

They found that the higher the CBD ratio, the better results.

Let's look at the primary symptoms of MS and CBD first:

• Spasticity - approximately 80% of patients
• Pain
• Inflammation
• Sleep Disturbance
• Depression

Again, much of the research is on THC and CBD combined to start.

First, spasticity:

In the THC-CBD group, 40% of patients reported at least a 30% improvement in spasticity compared with 20% in the placebo group

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710104/

Another larger study:

All patients with continuous data up to 52 weeks of treatment were analyzed. Of these patients, 90% (n = 55 patients) reported continued benefit over a mean treatment time of 334 (± 209) days on mean spasticity NRS score

Another study looked at pain and sleep disturbances for 1:1 ratios:

CBM was superior to placebo in reducing the mean intensity of pain (CBM mean change -2.7, 95% CI: -3.4 to -2.0, placebo -1.4 95% CI: -2.0 to -0.8, comparison between groups, p = 0.005) and sleep disturbance (CBM mean change -2.5, 95% CI: -3.4 to -1.7, placebo -0.8, 95% CI: -1.5 to -0.1, comparison between groups, p = 0.003).

https://pubmed.ncbi.nlm.nih.gov/16186518/

Improvements on both pain and sleep. See CBD and pain or CBD and sleep for more information.

We can look at mouse equivalent to MS called EAE (experimental autoimmune encephamyelitis) while we wait for researchers to catch up.

The results:

Treatment with CBD caused attenuation of EAE disease paradigms as indicated by a significant reduction in clinical scores of paralysis, decreased T cell infiltration in the central nervous system, and reduced levels of IL-17 and IFNγ.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085417/

More interesting is what was happening beneath the surface.

Interestingly, CBD treatment led to a profound increase in myeloid-derived suppressor cells (MDSCs) in EAE mice when compared to the vehicle-treated EAE controls.

Let's translate before it gets too confusing.

MDSC protect the mylin sheets from our immune system!

They turn down the T cell response that's attacking our myelin sheath.

This is profound in the research for MS.

Case in point:

When particular control cells are missing, too many B cells accumulate in the meninges, resulting in inflammation of the central nervous system.

https://www.eurekalert.org/pub_releases/2018-11/tuom-msa110818.php

What were those control cells?

This phenomenon did not occur when enough MDSCs were present, controlling the number of B cells.

Fascinating.

And CBD increased the numbers of these cells in a the mouse model of MS (EAE).

Remember the Vitamin D connection:

An increase of 25(OH)D levels by 50% decreased the odds of getting MS by approximately 50%

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990512/

Goodness...that should be front page news.

That article is an amazing review of Vitamin D and autoimmune by the way.

Next up...the thyroid.

CBD and thyroiditis

Also called Hashimoto's disease (too little thyroid activity) or Grave's disease (too much thyroid activity), we have to zero in on hormones here.

Graves tends to hit women before age 40 while Hashimoto tends to hit women after age 40.

• Graves disease: women outnumber men 7:1
• Hashimotos disease: women outnumber men 8:1

What gives there?

Part of it is progesterone. Progesterone levels drop steadily and reach 50% by age 40.

We did a massive review of progesterone and its powerful effect on immune response.

In general, progesterone calms the immune response (to protect fetus from being rejected).

As for the thyroid specifically:

Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454767/

Pregnancy shines a light on the direct effect of progesterone and autoimmune:

At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431799/

Read that back over. When progesterone spikes during pregancy, autoimmune diseases (some of the nastiest ones) calm down.

So...what about CBD?

We don't have research specifically on thyroid related autoimmune diseases.

What is known deals with inflammatory markets (immune response) and gut health.

As for the microbiome and thyroid autoimmune diseases:

An altered microbiota composition increases the prevalence of Hashimoto’s thyroiditis (HT) and Graves’ disease (GD).

https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(19)30107-9

We looked at how CBD supports the gut barrier and microbiome health but lets turn to immune response.

There are different immune response "settings" tied to various autoimmune diseases and an inflammatory one called TH17 is linked with Graves disease (and most autoimmune diseases):

Serum IL-17 and IL-23 levels were significantly higher in euthyroid HT individuals than in hypothyroid HT subjects and in the control group.

http://www.brainimmune.com/th17-contribute-hashimotos-thyroiditis/

What does CBD do for these inflammatory states?

cannabidiol (CBD), markedly reduce the Th17 phenotype which is known to be increased in inflammatory autoimmune pathologies such as Multiple Sclerosis.

https://pubmed.ncbi.nlm.nih.gov/23892791/

We look forward to more thorough tests on CBD directly and the host of autoimmune diseases.

See also CBD and dementia.

There's a great review of various aspects of CBD for autoimmune pathways here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173676/

Some practical questions.

How much CBD to take for autoimmune diseases

Unlike studies in mental health with CBD, dosage levels are less clear with autoimmune because we don't have as much double-blind, placebo research.

Most of the studies are on animals and dealing with discreet pathways such as inflammatory markers or immune response.

A study is scheduled for HIV patients and will range from 45-225 mg/day. The peak for neurogenesis is 300 mg.

Some of the animal studies were at much higher levels comparable to around 600-800 mg which reflects what research shows for more serious issues (see CBD and schizophrenia or CBD and public speaking for social anxiety).

As for the studies referenced above, they were at 5-10mg/kg (around 700-1500 mg).

We look forward to more definitive guidance on the dosage but targets of 200-300mg/daily appear within reason with 600mg matching early or more severe intervention from the study above.

Always work with your doctor or naturopath with CBD or any supplement!

Some other interesting tools to look at:

• Berberine - protects the gut barrier
• PEA (palmitoylethanolamide) - key supporter of endocannabinoid system
• NAC - powerful supporter of antioxidation pathway
• Vitamin D (get tested) - powerful manager of immune response and gut barrier protection

Our histamine toolkit mirrors this which makes sense since histamine is the forward guard of immune response:

What about the type of CBD?

What's the best CBD for autoimmune

First, there are basic requirements:

• Organically grown in the US at an FDA registered farm
• CO2 processed
• 3rd party tested
• No THC (THC build tolerance unfortunately)
• No pesticides
• No heavy metals
• No solvents
• No bacteria
• No mold

We test ours twice since our whole family uses it.

Then there's the whole CBD isolate versus CBD full spectrum which half the market is pushing.

All the research is on CBD by itself (isolate). The issue with full spectrum is that all the plant material can cause histamine responses especially if inflammatory states are high.

40-60% of the population has histamine issues and this number goes up as we get older and for women (Thanks, progesterone!) which dovetails with autoimmune risk.

Go figure.

Look at what happens when researchers block histamine response for autoimmune disease:

Treatment with the H4R antagonist resulted in a dose-dependent reduction in disease severity compared with vehicle-treated mice, as confirmed by histological examination

https://www.nature.com/articles/nrrheum.2013.169

We don't want to drive histamine response and full spectrum is a possible culprit there.

Look at our reviews and how many people mention that side effects from full spectrum goes away with CBD isolate.

Then there's the cost.

The research points to higher levels of CBD for autoimmune pathways. 300-600mg/daily.

The key there is cost per mg of CBD.

Our 6000 mg bottle is priced at 2-3 cents per mg before discounts up to 40-50% for this reason.

We found CBD as a result of suffering (that story is here) and we want to make it available to as many people as possible.

Related Research

CBD and neuroinflammation

CBD and gut barrier

CBD and asthma

How early trauma increases inflammation

Always work with a doctor or naturopath with any supplement!

The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.