We just wrapped a major review of CBD and autoimmune.
In that article, a fair amount of time is spent on gut inflammation and with good reason.
Most new research is showing that gut inflammation is Rome when it comes to system-wide inflammation across the body and brain.
All roads lead to Rome!
The gut operates like a thermostat to establish how strongly the immune system will respond.
We'll get into why gut inflammation is such an issue these days below but more importantly, we'll zero in on CBD's effect in this realm.
This may be one of CBD's greatest tricks for health in general.
Here are the topics we'll cover:
- A quick introduction to our second brain - the gut!
- How the gut sets immune response across the body
- What drives gut inflammation
- The effect of inflammation on the gut barrier (leaky gut)
- The microbiome's importance on managing gut health
- Research on CBD and gut inflammation
- CBD and IBD
- CBD and Crohn's
- CBD and gut barrier
- How much CBD to take for gut inflammation
- What's the best CBD for gut inflammation
Let's get started.
A quick introduction to our second brain - the gut
The gut is often called the "second brain" and with good reason.
It's the only other place outside of the brain where you have such a density of neurons.
That in itself is fascinating but it begs the question...why?
Originally, the need for a separate nervous system was thought to be needed to control the process and movement of food through the vast gut and GI tract.
New studies are showing that it communicates directly with the brain via the vagus nerve as part of our sympathetic nervous system.
Essentially, it's a vast "sensor" of what's going on internally while the brain is a vast sensor of what's going on externally!
That "gut feeling" is more than just a saying...it's real!
Serotonin just happens to be the feel-good master regulator of all human behavior (target of SSRIs) while dopamine is the primary driver of motivation and self-actualization (not to mention addiction).
Where things really get interesting is with the immune system and that's our lead-in to inflammation.
How the gut sets immune response across the body
The immune system is heavily integrated into the gut and for good reason.
Think about it…
If you're a nasty bacteria and want to gain entry into the body, what's the best way in?
The gut...literally a trojan horse inside the fortress.
For this reason, we have a complex and interwoven barrier against hostile forces in the gut barrier made up of three main barriers:
- The microbiome and their "film" - our gut bacteria actually serve to protect us first
- The actual lining of the gut - tight junctions that allow nutrients through but block attackers
- The immune responders - think of TSA security at the airports - carefully checking all "passengers"
When this barrier breaks down, bad things get across and the immune system is thrown into high alert.
We have a whole review on CBD and the gut barrier but this is where inflammation starts.
Where does it end?
- Autoimmune (proteins from bacteria mimic our own cell's proteins)
- Dementia - Amyloid-beta particles are actually members of our immune system
- Mental health issues - inflammation in the brain is tied to almost every mental issue in some aspect
We have a whole review just on CBD and probiotics for anxiety.
In terms of gut-to-brain signaling, there is emerging evidence from preclinical and clinical observation that intestinal inflammation alters brain functions, including the induction of mood disorders
Then, there's just systemic inflammation and the resulting slow assault that has on our general health.
Focusing down on the gut, a host of issues result from an inflammatory bent:
These are all hallmarks of an inflammatory gut environment and the resulting immune system over-response.
We have a huge review on CBD for IBD and IBS.
Before we jump into this, let's look at what is causing the issue to begin with.
What drives gut inflammation
Where do we start!
In our modern world, we are swimming in chemicals that disrupt the gut and microbiome.
- Fake sugars
- Additives and preservatives
- Pathogenic bacteria and viruses
We're not even talking about PFOA's (the "forever" chemicals) which even show up in umbilical cord blood now.
It's crowded in there:
n a study spearheaded by the Environmental Working Group (EWG) in collaboration with Commonweal, researchers at two major laboratories found an average of 200 industrial chemicals and pollutants in umbilical cord blood from 10 babies born in August and September of 2004 in U.S. hospitals.
In the mix…
Among them are eight perfluorochemicals used as stain and oil repellants in fast food packaging, clothes and textiles — including the Teflon chemical PFOA
Rather than just take our word at it, let's drill down into a few examples (of 1000's) from the categories above.
researchers from Case Western Reserve University School of Medicine and colleagues have found that, given over a six-week period, the artificial sweetener sucralose, known by the brand name Splenda worsens gut inflammation in mice with Crohn's disease
The gut barrier:
At high concentrations, aspartame and saccharin were found to induce apoptosis and cell death in intestinal epithelial cells, while at low concentrations, sucralose and aspartame increased epithelial barrier permeability and down-regulated claudin 3 at the cell surface.
So weakened barrier and more bad gets through.
Additives and preservatives:
mice given the emulsifiers carboxymethylcellulose and polysorbate 80 develop dysbiosis with overgrowth of mucus-degrading bacteria.
The fascinating piece of that study is this...the immune system misreads a protein in the preservative for one that belongs to bacteria it's on the lookout for:
Such an effect triggers colitis in animals deficient in either interleukin-10, a cytokine exerting anti-inflammatory and regulatory functions, or Toll-like receptor 5, a receptor recognizing the bacterial flagellin.
This sets off a cascade of inflammatory responses but only if there's a missing piece of anti-inflammatory activity (IL10...we'll get to that with CBD).
Sugihara et al. fed Sprague–Dawley rats with a diet containing 0.5% to 1.5% phosphate for 7 days before colitis induction
In a recent study, maltodextrin in drinking water exacerbated intestinal inflammation in an indomethacin-induced enteropathy model or in DSS (Dextran sodium sulfate)-colitis.
In addition, long-term exposition for 100 days is associated with low-grade colon inflammation and induced aberrant crypt foci in a chemically induced carcinogenesis model
Okay...what about our favorite...in almost every cereal...BHT - a petroleum derivative.
butylated hydroxyanisole/butylated hydroxytoluene (BHA/BHT)43 were previously linked to metabolic, gut microbiota or endocrine perturbations along with carcinogenic, inflammatory and/or oxidative stress effects.
No fair using Vitamin E in the same role for a few cents more.
Can we stop now?
Look...our hardware (and immune system software) is 100's, 1000's, and even millions of years old.
If it doesn't recognize a new chemical created in the last 50 years, it's probably going to see it as foreign and potentially dangerous.
Hence the immune response!
What about pesticides?
Pesticides, by definition kill bacteria.
The problem is that our gut microbiome is made of trillions of bacteria that research now treats as important as being a separate organ to our health.
A healthy microbiome is directly tied to countering inflammation in the gut, body, and brain.
Let's look at our favorite one...glyphosate.
It's used in roughly 90% of all US soy, corn, and wheat that's not organic.
- Small intestinal oxidation and inflammation were induced by glyphosate exposure.
- Ion imbalance was induced in the small intestine by glyphosate exposure.
- Glyphosate exposure altered gut microbial composition.
- Glyphosate exposure significantly decreased the relative of Lactobaillus.
Guess what bacteria don't get affected:
To the contrary, Clostridium spp. and Salmonella strains are shown to be resistant to Glyphosate
C diff is the nasty bacteria you hear about in the news that can wreck your gut and is very hard to get rid of.
We'll cover CBD's effect on C diff later.
And remember...the gut is the gateway to the rest of the body:
The overgrowth of bacteria such as clostridia generates high levels of noxious metabolites in the brain, which can contribute to the development of neurological deviations.
What about celiac disease (a form of gut inflammation) and diabetes?
Fish exposed to glyphosate develop digestive problems that are reminiscent of celiac disease. Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glyphosate on gut bacteria.
After adjusting for gender, age, BMI, cigarette smoking, alcohol consumption, family history of diabetes, and occupation, it was found that the prevalence of diabetes was positively associated with exposure to all types of pesticides, including insecticides, herbicides, fungicides, rodenticides, and molluscicides, with exposure to rodenticides being statistically significant
Glyphosate ramps down one of the most important liver pathways we have called p450.
And to wrap it up (please!!), from very recent research:
Glyphosate exposure induces inflammatory responses in the small intestine and alters gut microbial composition in rats
Goodness. It's banned in Europe but flying off the shelf in every US grocery store.
Many very popular medications, both prescription and over-the-counter directly affect gut inflammation and the barrier itself.
- NSAIDs (Motrin, etc) and Tylenol
- Proton Pump Inhibitors
Just to name a few examples.
It's fascinating because everything you put in your mouth causes re-shifting of the bacteria make-up in your gut.
Some go up while others go down.
This can change after just one meal!
We've looked at studies where mice will put on weight after gut bacteria alterations with the same food intake and activity!
Gut inflammation is important in its own right but the consequences span the body. This is so important that we need to touch base quickly.
How the gut sets immune response across the body
Inflammation is just a response by our immune system...generally to attackers.
Rogue bacteria and viruses that gain access to our bodies.
If we have chronic gut inflammation, this directly leads to a hyperactive immune response throughout the body.
In fact, researchers know that we have "settings"...the two most common are TH1 and TH2.
- TH1 is generally inflammatory
- TH2 is generally anti-inflammatory...or better yet, used to "resolve" inflammation.
Inflammation was never intended to be a long-term state without doing damage.
The bigger issue is autoimmune.
Most of our modern diseases are autoimmune in nature...and it's directly tied to gut inflammation.
Here's the process as we outline in our CBD and autoimmune deep-dive.
- Inflammation breaks down the gut barrier
- Bacteria and viruses are able to escape the gut into our body (and brain if the brain barrier is weakened as well)
- The immune system ramps up an attack
- The proteins from various bacteria/viruses can be similar to proteins naturally found in our body (such as synovial cells in our joints with rheumatoid arthritis).
- The immune system mistakenly attacks our own cells!
The hole in the dam that starts this whole process is our gut barrier (and mouth, reproductive, etc).
Inflammation is the original sin to this whole process.
We'll look below at CBD and other substances that can support the gut barrier directly.
Before we jump to CBD, let's take a pitstop in the microbiome...the varied array of bacteria that help us function in the gut.
The microbiome's importance on managing gut health
Inflammation is both the cause and effect of gut bacteria getting out of balance.
The research is pretty clear now:
Intestinal inflammation and inflammatory bowel disease (IBD) are commonly associated with dysbiosis of the gut microbiota.
Scientists now know that the different species of bacteria have separate roles and effects on the gut.
They even differ as you go through the roughly 18 feet of GI tract.
They affect every aspect of our metabolism (fat, energy, glucose, etc).
Probiotic Bacillus treatment substantially attenuated body weight gain and enhanced glucose tolerance by sensitizing insulin action in skeletal muscle and epididymal adipose tissue (EAT) of HFD-fed mic
HFD is a high-fat diet.
You can take certain strains out and cause anxiety. You can remove other strains and reduce anxiety.
It's fascinating as research is really showing that our gut bacteria directly drive our actions, wants, and behavior.
We did a big review on CBD, probiotics, and anxiety going into specific strains.
Then, there are the bad players.
Nasty strains of bacteria that try to gain a foothold.
E. coli (the bad version of many). C diff. A host of others.
Some bacteria strains are highly inflammatory to our guts.
As we saw above, some common food additives actually hurt our good bacteria but don't affect the bad ones.
Our good bacteria actually crowd out foreign pathogens and form a mucus layer on our gut barrier to protect it.
We've set the stage now.
- Environmental agents (chemicals, pesticides, etc) can damage the bacteria mix in our gut
- Our immune system responds by attacking (it's role after all)
- With chronic immune response, we have chronic inflammation which leads to disease states
Let's look at how CBD affects these.
Research on CBD and gut inflammation
Before we jump into inflammatory diseases of the gut, let's look at the following pathways:
- CBD and gut immune response in the gut
- CBD and gut inflammation
- CBD and gut microbiome
- CBD and gut barrier
Let's get started.
CBD and gut immune response in the gut
First of all, CBD generally has an anti-inflammatory response when states are high.
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.
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!
Remember how there's a shift to more inflammatory states (TH1) with various diseases?
Look at CBD's effect from studies on diabetes:
CBD-treated mice exhibited significant reduction of plasma levels of the proinflammatory cytokines IFN-γ and TNF-α, whereas production of the Th2-associated cytokines IL-4 and IL-10 was increased when compared with untreated control mice, thus shifting the immune response from Th1 to Th2 dominance
Essentially, CBD reduced inflammation and boosted the immune "resolvers" such as IL10 which we know is deficient in people that develop chronic gut inflammation.
This "shift" from TH1 to TH2 is the holy grail with inflammation. Stand down!
Now, we still have to fix the gut barrier and remove the chemicals, medications, pesticides that keep tripping the alarm but inflammation lies solely in this shift.
We have to get a little technical now.
Let's introduce a pathway called PPAR. It's a powerful anti-inflammatory pathway in the body and gut.
Why even go into the realm of letters stacked together?
Recent data showing that PPARγ was the major functional receptor mediating the common aminosalicylate activities in inflammatory bowel diseases (IBD) have also reinforced the roles of this receptor in the control of intestinal inflammation.
The key words there are "control of intestinal inflammation"
PPAR is now considered almost the third endocannabinoid receptor (the other 2 are CB1 and CB2).
CBD's effect on PPAR?
The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients.
To translate...CBD operated on this PPAR pathway to counter gut inflammation in colitis.
We did a big review on PEA which also works here. CBD and PEA may be powerful allies.
Remember how we said that our good gut bacteria are busy fine-tuning aspects of our health?
Turns out they interact with PPAR as well!:
Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmicshuttling of PPAR-γ and RelA
They are literally turning on PPAR pathways to tamp down inflammation...till we wipe them out with pesticides, chemicals, medications, and overcrowding bad bacteria.
Then there's anandamide, the primary endocannabinoids naturally in our bodies.
It's the ultimate anti-inflammatory.
anandamide is elevated in the inflamed colon of patients with ulcerative colitis, as well as in animal models of IBDs, to control inflammation, and elevation of its levels with inhibitors of its cellular reuptake might be used in the treatment of IBDs.
The effects of boosting anandamide?
5-ASA also increased anandamide levels and abolished colitis.
CBD's effect on anandamide from a study on schizophrenia?
Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement.
This is why so many people use cannabis...THC is a substitute for anandamide.
The problem is that THC only pushes in one direction. The body then pushes back!
We see this effect across a range of chemicals such as benzos for GABA and SSRIs for serotonin.
Eventually, you end up with less of that pathway than when you started!
For example, with longer-term THC use, the body will start to reduce both the numbers and sensitivity of CB1 receptors.
That's bad news for gut inflammation based on what we saw above.
CBD works like a feedback mechanism to support when a given pathway is too high or too low.
This really is the beauty of its effect.
Okay...so let's cut to the chase. Research on CBD and gut inflammation.
CBD and gut inflammation
Remember how we said that NSAIDs (Ibuprofen, Tylenol, etc) can disrupt the gut and lead to inflammation?
A study looked at an interesting mechanism to offset this damage:
Dual inhibition of FAAH and cyclooxygenase enzymes induces protection against both NSAID-induced gastrointestinal damage and intestinal inflammation.
Stay with us...we'll explain.
FAAH is going to be a big deal in the next 10 years as CRPSR gene editing comes online.
Check out our review of the woman who can't feel pain, anxiety, or depression due to a lack of FAAH.
FAAH eats up anandamide which we discussed above.
When you block it, NSAID damage was protected against.
It's a workaround to boosting anandamide but it's one we can take advantage of.
CBD and PEA!
From a study on Parkinson's:
CBD also inhibits FAAH, which results in increased anandamide levels.
You actually see this effect across a range of issues since anandamide is the great re-balancing actor in the body and brain from stress.
A double-blind, placebo study looked at CBD and PEA for hypermotility (GI tract moving too fast - diarrhea, etc) and the results:
In vitro, PEA, and CBD decreased the inflammation-induced flux of dextrans (P < 0.0001), sensitive to PPARα and CB1 antagonism, respectively.
So, dextrans are known to cause inflammation in the gut. CBD and PEA offset this.
What was the secret sauce? Take a guess:
Palmitoylethanolamide and cannabidiol prevented an inflammation-induced fall in TRPV1 and increase in PPARα transcription
TRPV is another interesting pathway that CBD directly affects.
There's PPAR again.
The results involved the gut!:
existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation.
"Regulating gut bacteria". Gut permeability (breakdown of barrier). Goodness. drop mic now!
Let's go there now.
CBD and gut microbiome
We're finally getting some new research on CBD and gut bacteria.
A study looked at fish oil and CBD combined:
FO and CBD co-administered at per se ineffective doses reduce colon inflammation, in a manner potentially strengthened by their independent elevation of Akkermansia muciniphila.
Akkermansia muciniphila is a very interesting type of gut bacteria.
Look at this:
Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (−34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (−8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (−2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (−1.37 ± 0.82 kg, P = 0.092) and hip circumference (−2.63 ± 1.14 cm, P = 0.091) compared to baseline.
To translate...against placebo, supplementation of this improved the entire metabolic profile and weight/body mass.
No change in calories or activity. Just one species of gut bacteria.
Fish oil and CBD support this specific species.
To see just how deep the rabbit hole goes for gut control over our health:
Low Relative Abundances of the Mucolytic Bacterium Akkermansia muciniphila and Bifidobacterium spp. in Feces of Children with Autism
Huge review on CBD and autism.
What about supplementation for children with autism?
After probiotic supplementation, the stool PCR of autistic children showed increases in the colony counts of Bifidobacteria and Lactobacilli levels, with a significant reduction in their body weight as well as significant improvements in the severity of autism (assessed by the ATEC), and gastrointestinal symptoms (assessed by the 6-GSI) compared to the baseline evaluated at the start of the study
Sorry...we digress but just to impart the importance and almost complete ignorance of science on the power of the microbiome.
From a study on MS:
Examination of the colon revealed that the THC plus CBD treatment restored the gut microbiome that had been distorted by the EAE. The main effect was to reduce the abundance of Akkermansia muciniphila (A. muc).
We already explained why THC has a short term effect (boost anandamide) but CBD doesn't build tolerance!
In this case, the mouse model of MS had too much A municiphila.
Again,...it's about balance and the endocannabinoid system (where CBD works) is the main actor there (hence anandamide, FAAH, CBD, THC, etc).
One final stop before we look at diseases tied to gut inflammation.
The barrier between us and them (Them being trillions of bacteria, viruses, etc that make into our bowel).
CBD and gut barrier
We did a huge review of CBD and leaky gut.
Some quick takeaways that are important for gut inflammation.
Let's start with C diff...the nasty bacteria that can wreck havoc on our gut barrier.
Researchers exposed gut lining cells to C diff and the resulting damage is well known.
First the bad news:
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
Essentially, C dff killed off the cells and reduced the proteins needed to keep a tight barrier in the gut.
All these effects were significantly and concentration-dependently inhibited by cannabidiol
Let's turn to practical questions now.
How much CBD to take for gut inflammation
We're still awaiting trials with CBD as sufficient doses.
A study at 50 mg daily did not have much effect although the participants reflected positive results.
Studies on neurogenesis (brain repair) are at 300 mg daily.
Our best estimate is between 100-300mg for gut health with about 2 weeks needed for effects to build.
Even at 100 mg, there was an improvement in the gut barrier with IBD in one study.
What about the type of CBD?
What's the best CBD for gut inflammation
First, the basic requirements for all CBD:
- Organically grown in the US at FDA registered farms
- Co2 processed
- 3rd party tested
- No THC (more on this below)
- No solvents
- No pesticides
- No mold
- No bacteria
- No heavy metals
Why no THC if so much of the literature is on cannabis?
THC becomes too much of a good thing.
Essentially, it pushes CB1 activity (which is good) in one direction (up up up) which is why it can have side effects. We did a huge review of CBD and THC in the brain for starters!
The body doesn't like this and pushes back as we mentioned above.
It will actually compensate for this (if longer-term) by downregulating CB1 receptor numbers and sensitivity.
This is going in the wrong direction. Technically it's the basis for tolerance (see CBD and tolerance).
CBD does not do this! It's technically called a reverse allosteric modulator.
A feedback mechanism!
Rather than sending a signal to boost (such as THC with CB1 activity), CBD sends a message backwards.
- We need more CB1 activity, continue on.
- We're all set here...stop boosting.
This really is the beauty of CBD in our endocannabinoid system and speaks to why you don't see overdoses at very high levels.
Then there's the question of full-spectrum CBD versus CBD isolate.
Interestingly, women get hit much harder by gut inflammation diseases (thank progesterone for leaving the scene by 50% at age 40).
Age is also a factor (progesterone again).
This demographic is also very likely to have histamine issues (again, progesterone - really read up on this) which leads to side effects with full spectrum (all the plant material).
Keep in mind that histamine is the canary in the coal mine for inflammation!
We discovered this the hard way after trying 3-4 of the biggest CBD brands which all push full spectrum.
We covered why this is bogus at our CBD isolate versus full spectrum.
That and all the research is on CBD by itself. We're big fans of research if you haven't noticed.
Finally, there's cost.
If the given range is between 100-300mg daily, we need to be able to afford this.
The key there is the cost per mg of CBD.
We price our 6000mg bottles at 2-3 cents per mg of CBD before discounts up to 30% for that reason.
If you read our founder's story here, it's really important that we support people who are suffering.
We'll have major reviews of the common gut inflammation diseases shortly but you now have a good understanding of how CBD directly affects the pathways therein.
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.