We just wrapped a giant review of CBD and gut inflammation.
What a great lead-in for our next deep dive.
IBD and/or IBS are literally wrapped around gut inflammation.
Intestinal bowel disease or intestinal bowel syndrome are umbrella terms for a host of inflammatory states in the gut.
They include colitis, Crohn's disease, celiac, and more.
Inflammation is a key component and we're going to really get to the heart of how that process occurs.
More importantly, we'll look at how CBD and other tools affect this pathway.
The new research on Vitamin D is fascinating in itself and we'll cover that as well.
Finally, very recent research points to the pathway of histamine as a key driver in IBD directly.
Brand new research.
These are the topics we'll cover:
- What is IBD (IBS)
- How does inflammation in the gut start
- The microbiome and IBD
- The immune response in the gut with IBD
- The new histamine research for IBD
- Can CBD help with IBD and gut inflammation?
- How does Vitamin D affect IBD plus other tools?
- How much CBD for IBD
- What's the best CBD for IBD
Let's get started!
What is IBD (IBS)
Simply put, IBD is a deterioration in the gut-driven by chronic inflammation.
Keep in mind that inflammation is a function of our immune response which is primarily tasked with removing foreign entities such as bacteria and/or viruses.
We can add a new layer to this with a slew of manmade chemicals which we'll touch on in the next section.
There are some interesting characteristics to take note of which shed light on the underlying issue:
- Developed world versus developing world
- Gender effects for IBD and IBS
- Age factors for IBD and IBS
- Racial differences and IBD/IBS
Let's start with the location.
Why is there a much higher percentage of people developing IBD/IBS in developed countries UNTIL the developing counties become "westernized"?
Diet is a big factor with pesticides, chemical additives, and more.
We looked at that deeply in our gut inflammation study.
Cold climates also drive rates higher which clearly points to the Vitamin D effects (we'll get into that separately below).
Interestingly, the highest rates of incidence are in Canada (developed and Northern - less sunlight).
Don't underestimate the powerful immune modulation effects of Vitamin D.
What about gender?
Women are hit especially hard and we're not surprised.
After all, our entire site started from a brutal perimenopause (see here).
Estrogen is not just for reproduction:
ERβ is expressed abundantly in the colonic epithelium, where it has an established role in maintaining colonic architecture, tight-junction formation, and barrier function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924746/
Goodness...at the intersection of all things gut-related.
Check out our review of estradiol to learn more.
Progesterone is also a master regulator (calming agent more like it) for immune response and it's down to 50% by age 40!
Look at periods of time when progesterone is very high such as during pregnancy:
Many chronic pain syndromes frequently associated with IBS, like migraine headache for example, are alleviated during the time of pregnancy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949254/
This is just a quick sampling of many different pathways directly driving IBD and IBS for women.
Interestingly, this gender difference was reversed in Asia.
Our only guess is that the high concentration of phytoestrogens via soy (without the glyphosate, thank you) makes the difference.
It also leads us to our next section.
Age factors for IBD and IBS
IBD or IBS usually occur between 15 - 35 or in the '50s and 60's.
Why?
Puberty at the start and menopause at the end (for women).
Remember, women are hit at a much higher rate:
IBD was more prevalent in females compared with males (417 versus 284 per 100,000; relative risk, 1.53; 95% confidence interval, 1.50-1.57). There was an increased prevalence of IBD with each decade of life.
https://pubmed.ncbi.nlm.nih.gov/23518811/
As we mentioned, progesterone drops through the '30s and '40s and estrogen falls off a cliff by 50.
This is tied to a whole complex of issues including autoimmune, cardio, and mental health changes.
See CBD and autoimmune or CBD and mental health to learn more.
So when your doctor says your hormones are "fine for your age"...find a new doctor!
Also, systemic inflammation increases as we get older.
We cover this in our groundbreaking (yes, we're pretty excited about it) review on longevity.
That's why IBD increases with every decade of life regardless of gender.
What about race?
Racial differences and IBD or IBS
Caucasians are the big winners (losers??) here:
IBD was more common in Caucasians (324 per 100,000) compared with blacks, Asians, Hispanics, and American Indians (239, 162, 147, and 224 per 100,000, respectively
https://pubmed.ncbi.nlm.nih.gov/23518811/
Genetics can factor into there but it also speaks to Northern climates and Vitamin D levels.
Skin color is almost entirely driven by sunlight filtering for adequate Vitamin D.
Let's zero in on the process of gut inflammation which leads to this host of nasty conditions.
Thank modern science.
How does inflammation in the gut start and grow
Inflammation is just a weapon of our immune system.
It's there to defend against foreign entities that might hurt us.
There is a whole process of responding to a threat (pretty destructive with collateral damage) and then repair.
The issue is when the inflammatory response is chronic.
So the question is….what exactly is causing systemic inflammation in our gut?
Before we look at calming inflammation in the gut, let's first turn off the spigot
We'll look at these causes:
- Pesticides (like glyphosate)
- Chemical additives to food
- Medications
- Stress (especially chronic)
- Alcohol and drugs
- Pathogenic bacteria, mold, and other intruders
We'll give some quick examples.
Glyphosate and IBD or IBS:
Glyphosate exposure induces inflammatory responses in the small intestine and alters gut microbial composition in rats
https://www.sciencedirect.com/science/article/abs/pii/S026974911936141X
There's interesting new information on how glyphosate upsets a specific pathway called the shikimate pathway.
This is how our gut bacteria process a range of nutrients and manufacture key metabolites:
Methionine, an essential sulfur-containing amino acid, and glycine are also negatively impacted by glyphosate. Furthermore, many other biologically active molecules, including serotonin, melatonin, melanin, epinephrine, dopamine, thyroid hormone, folate, coenzyme Q10, vitamin K, and vitamin E, depend on the shikimate pathway metabolites as precursors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392553/
- Um...serotonin (master regulator of all human behavior)
- Dopamine - just your motivation neurotransmitters.
- Folate - B vitamin needed for so many different processes
- Thyroid? Weight, energy, metabolism. A big issue these days.
Goodness.
That's an interesting article with a slew of different negative effects.
Science is finally understanding just how important our gut bacteria (see CBD and the microbiome) are.
It's literally like a separate organ in terms of good health.
Chemical additives to food and the environment
This is well-known but good luck getting any regulation on this front with the 1000's of chemicals used in food and products.
The 40K foot view:
Common additives in ice cream, margarine, packaged bread and many processed foods may promote the inflammatory bowel diseases ulcerative colitis and Crohn’s disease as well as a group of obesity-related conditions, scientists said on Wednesday.
Remember the risk of developing nations?
Consumption of ultra-processed food (UPF) has increased over the last decade, in particular in industrialized societies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567822/
And…
the authors also reported an association between these dietary patterns and a higher irritable bowel syndrome risk
There are too many examples to list.
What about RX drugs?
Medications and IBD/IBS
We're finally understanding how RX drugs will affect gut health and inflammation.
Many people have no idea of these links.
A few examples for very common drugs.
NSAIDs (avid, motrin, etc)
To the point:
NSAIDs provoke disease activity in both UC and CD. NSAIDs are associated with hospitalizations for severe colitis in patient with IBD. NSAIDs use was not associated with higher likelihood of active IBD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034022/
Most importantly, when doses go up, disease factors go up.
A clear indication of causality.
Check out CBD versus Tylenol to learn how it works in the pain pathway.
Let's talk about stress.
Stress (especially chronic)
There's a known connection to both stress and the development and even flare-up of IBD.
We have to understand that the gut is intimately tied to our brain and hormone system.
The gut is the residence for the highest number of neurons outside of the brain.
In fact, it's called the "second brain" for this reason.
The new are intimately tied together via the vagus nerve which sits right behind your breastplate.
Newer studies are starting to tease out the connections with stress:
The underlying mechanisms consist of immune dysfunction, intestinal microbiota disturbance, impaired intestinal barrier function, and neuroendocrine system alterations
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821654/
One of our preeminent stress response buffers is serotonin. In fact, most of our serotonin is made in the gut!
Stress will eat up serotonin which speaks to the tie between IBD and depression:
Thus, depression and IBD share a common pathway that seems to explain the interaction between the two diseases.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821654/
The anti-nausea drugs and many GI medications are nothing but serotonin boosters.
Stress' response:
Sustained or chronic stress, in particular, leads to elevated hormones such as cortisol, the "stress hormone," and reduced serotonin and other neurotransmitters in the brain, including dopamine, which has been linked to depression.
https://www.webmd.com/depression/features/stress-depression
Interestingly for CBD, the master stress-response system is the endocannabinoid system in which CBD works.
We'll get into that below but checkmark next to this!
Alcohol and drugs
Many drugs including alcohol and opiates adversely affect the gut and IBD/IBS.
Alcohol consumption is a potential trigger for flare in Inflammatory Bowel Disease (IBD) flare because of alcohol’s pro-oxidant effects and its deleterious effects on gut barrier function.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708696/
We'll look at how to address oxidative stress and gut barrier with CBD.
What about opioids?
Speak of catch 22!
Roughly 30% of people with IBD are prescribed opioids for the pain.
The net effect of longer-term use?:
Chronic opioid treatment reduces gastrointestinal transit via effects on μ-opioid receptors, resulting in an altered microbiome. Changes in the microbiome disrupt epithelial permeability enabling bacterial translocation and systemic inflammation that could enhance the development of antinociceptive tolerance.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045338/
This bad news. Basically, chronic use leads to leaky gut (see CBD and leaky gut) and chronic inflammation...the very thing at the heart of IBD>
It also builds tolerance which means that pain relief becomes less and less with time.
See CBD and opioid addiction for more on this.
Nicotine's interesting.
Nicotine has been shown to prevent colitis but obviously, the other health effects are not worth the risk.
Here's the deal...the real star behind nicotine is acetylcholine.
In fact, people who really love nicotine (chain smokers) are probably self-medicating for lacking acetylcholine.
- You can easily supplement choline.
- Here's the interesting piece tied to our discussion.
Remember the vagus nerve which connects the gut and brain?
Its primary output is….acetylcholine!
It gets better...acetylcholine is the primary neurotransmitter for the parasympathetic nervous system.
The rest and digest system as opposed to our fight or flight system.
The latter is essentially stress! Cortisol. Histamine. Jump!
Look at research connecting this all together:
Tracey and coworkers demonstrated that stimulation of the parasympathetic nervous system via the vagus nerve led to lower cytokine production and increased survival in a rodent model of sepsis, introducing the novel concept of the ‘cholinergic anti‐inflammatory pathway’
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063935/
Essentially, if you're constantly in a state of discount fight or flight (stress), the delicate balance of inflammation in the gut AND nervous system goes haywire.
Learn all about acetylcholine here...especially if you're constantly "frazzled".
What about supplementation for deficiency?
Insufficient dietary choline aggravates disease severity in a mouse model of Citrobacter rodentium-induced colitis
That's a great segue to our next section.
Pathogenic bacteria, viruses, and other intruders
Nasty bacteria and viruses can gain entry into our gut and set off a range of IBD diseases.
The Citrobacter Rodentium.
Humans have their own version of very nasty bacteria.
E Coli (the bad versions). C diff.
These and others can wreck our guts natural bacteria balance and the results?
At different taxonomic levels, the structure of the gut microbiota is significantly altered in IBD patients compared to that of healthy individuals.
https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-019-0341-6
Here's a quick look at just a few:
The most indispensable pathogens that could be associated with the IBD disease, Mycobacterium avium subspecies paratuberculosis, Clostridium difficile, Escherichia coli, Listeria monocytogenes, Campylobacter concisus; as well as viruses, such as, cytomegalovirus, Epstein-Barr Virus, and measles virus are notable
https://pubmed.ncbi.nlm.nih.gov/29508438/
Let's just look at C diff since it's a really home-wrecker.
Unfortunately, this is on an uptrend (we'll explain why in the next section):
The burden of C. difficile infection (CDI) has increased dramatically over the past decade and it is now recognized that C. difficile is responsible for 20%-30% of cases of antibiotic associated diarrhea and 50%-75% of cases of antibiotic associated colitis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837256/
The big question is this...why is C diff and other nasty bacteria infections rising over time?
Sure, antibiotics figure into this but we have to understand the microbiome's role in protecting us a bit first.
The microbiome...our vast inner zoo of bacteria, yeast, and others!
The microbiome and IBD
We need a moment of deference for the unique living world in our gut.
It's vast (and mostly undiscovered):
The human gut microbiota contains about 1014 bacterial cells from more than 1000 different bacterial species[1,2] that play an important role in conservation of mucosal innate and adaptive immune function, integrity of the epithelial barrier and nutrient absorption
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837256/
Goodness...trillions of bacteria (mainly) with a 1000 different species that control the immune response, protect bad actors from entering our body, and actually process key nutrients for the body and brain.
Studies can literally affect a type of bacteria and turn up or down key neurotransmitters or nutrients in our body and brain.
When bad actors like c diff gain entry to our gut, it's the crowding out and competition with our protective gut bacteria that keep them at bay.
It's a zero-sum game in the gut.
If one bacteria explodes in numbers, it's usually at the expense or "die-off" of another species.
Our bacteria mix changes depending on where you are in the gut and with every meal you eat.
Meat versus vegetables benefits some while reducing other species.
Bacteria like c diff can gain a foothold and really create imbalances and a host of gut issues (followed by body/brain issues).
The chemicals, additives, pesticides, etc above all hurt our microbiome balance which leads to inflammation.
Let's touch on this aspect of immune response before jumping into CBD's effect.
The immune response in the gut with IBD
There are two powerful aspects of the gut immune response to look at:
- Inflammation in response to bad bacteria viruses
- Histamine response in response to unknown chemicals
The first is pretty explanatory.
When our immune response recognizes actors like c Diff, it responds with brute force to attack it.
If there's a c diff foothold, this leads to long-term inflammatory responses which is the basis for IBD.
The second piece is more fascinating and the research is brand new (Jan 2020).
Let's go there!
The new histamine research for IBS
Here's the breakthrough study:
https://www.uzleuven.be/en/news/scientists-reveal-mechanism-causes-irritable-bowel-syndrome
Essentially, with food poisoning or other chemicals, the body doesn't recognize, a sizeable histamine onslaught occurs in the gut.
It's called a mast cell activation and we covered it at our CBD and mast cell syndrome.
Essentially, a massive allergic reaction in the gut.
This makes sense since the role of histamine is to get bad things out of the body FAST!
Here's the part that's important:
When food antigens associated with IBS (gluten, wheat, soy and cow milk) were injected into the intestine wall of 12 IBS patients, they produced localized immune reactions similar to that seen in the mice. No reaction was seen in healthy volunteers.
This histamine response was the difference!
Women progressively find they can't take certain things (cosmetics, food, etc) as they get older.
This makes complete sense since progesterone is a major calming agent for the immune system (to protect amniotic sac during pregnancy when it spikes) and it drops by 50% at age 40 and continues down from there.
Hence, the autoimmune and other issues that creep up during the '40s into menopause.
Men and women slowly lose their ability to process Vitamin D through the skin which also contributes to a general heightening of immune response including histamines.
We'll touch on that below since it's easy to fix.
Again, decades of exposure to pesticides (glyphosate or equivalent is used in around 90% of US-grown corn, wheat, and soy), chemical additives, antibiotics, fake sugars/fats, and more is priming our immune response to over-react.
You can check out CBD and gut inflammation or CBD and mast cell activation to learn more.
That's the bad news...what about some good news!
Can CBD help with IBD and gut inflammation?
You can learn how CBD works exactly here in general terms but let's zero down into these core questions from above:
- CBD and gut inflammation for IBD and IBS
- CBD and the microbiome
- CBD and immune response for IBD/IBS
- CBD and histamine or mast cell response for IBS
- CBD and IBD and IBS research
These are the key components so let's break them down.
CBD and gut inflammation for IBD and IBS
CBD has a known anti-inflammatory effect across the body.
What about the gut?
Researchers looked at CBD's effect on gut cells from people with ulcerative colitis and mice with triggered gut inflammation after adding bad bacteria:
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/
The scientist found that a range of inflammatory agents were brought down as an effect and the main pathways was via PPAR.
The net effect of this activity:
These actions lead to a reduction of intestinal damage mediated by the PPARgamma receptor pathway
PPAR is a powerful pathway in the gut:
PPARγ is highly expressed in the colon and a key receptor in the regulation of intestinal inflammation induced by bacteria.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860011/
CBD and PEA both work within this pathway. Check out the full review on PEA here.
Does CBD impact the gut microbiome… our protective bacteria?
CBD and the microbiome
We're finally getting some good research on this front.
Scientists took a fecal transplant with THC and CBD to test the results in EAE, a mouse model of MS.
The results:
Fecal transfer of THC + CBD-altered microbiome attenuate EAE disease severity. Cannabinoids suppress EAE through regulation of microbiota.
https://www.sciencedirect.com/science/article/abs/pii/S0889159119306476
This is important because it shows that the effect was due to changes in the microbiome.
We covered CBD versus THC here. The issue with THC is that the body builds tolerance and it only pushes in one direction (suppress immune response).
CBD doesn't build tolerance and it works like a feedback mechanism.
This is very important because we actually want inflammation when bad bacteria attack.
That's the issue you see with immunosuppressors like the TV ads.
A fascinating look at how alcohol addiction drives negative changes in the gut microbiome with the following effects:
Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability.
https://pubmed.ncbi.nlm.nih.gov/31803950/
The net effects of this?
These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control.
MGBA is short for the microbiota-gut-brain axis. Basically the connection with our gut bacteria and our brain.
CBD's result there?
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.
We did a huge review of CBD and alcohol addiction or CBD and addiction.
Speaking of the immune response.
CBD and immune response for IBD/IBS
The immune response is so complex.
Let's focus on two key players.
We have a series of inflammatory agents called cytokines and another set of antiinflammatory agents (also called cytokines).
In fact, there are two general settings:
- TH1 - inflammatory
- TH2 - resolution of inflammation, calming
This is a very simple generalization of a ridiculously complicated system.
Let's look at CBD's effects on cytokines in states of high inflammation (asthma in this case):
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.hindawi.com/journals/mi/2015/538670/
What's up with IL10? It happens to be an anti-inflammatory cytokine!
Then the TH1 and TH2 general setting.
cannabinoids may affect immune responses and host resistance by perturbing the balance between the cytokines produced by T-helper subsets, Th1 and Th2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/
We could quickly go down the rabbit's hole with the family of cytokines but this general setting up top is very indicative.
As for THC, quite by surprise:
Interestingly, while the anti-inflammatory cytokine IL-10 decreased following THC treatment, there was an increase in the proinflammatory cytokine IL-8.
Again...you don't want to push any pathway in one direction long term like THC does with CB1 activity.
Let's turn to the new research on histamine and IBS.
CBD and histamine or mast cell response for IBS
As we noted above, brand new research is pointing to histamine response from mast cells as the driver of IBS flare-ups.
Histamine is part of the immune response tasked with getting bad things out.
We've covered CBD's effect in this pathway at our CBD and mast cell activation syndrome or CBD and histamines.
Some quick takeaways.
Stay with us on this...we'll explain as we go.
First…
CBD markedly counteracted reactive enteric gliosis in LPS-mice through the massive reduction of astroglial signaling neurotrophin S100B.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190/
Okay...they introduced bad bacteria signals (LPS) into mice guts which caused an inflammatory response.
CBD countered this with a reduction in a chemical called s100B.
Here's the payoff for histamine in the gut:
S100B decrease was associated with a considerable decrease in mast cells and macrophages in the intestine of LPS-treated mice after CBD treatment.
Mast cells are where histamine gets released (exploded from is more apt) from.
CBD calmed the histamine response and we see this across the body.
At the heart of calming the histamine response is anandamide, our "bliss" molecule.
It's a known player in downregulating the activity of mast cells even in the gut.
Let's finally turn to CBD and IBD or IBS directly.
CBD and IBD and IBS research
The anandamide point before is a great starting point here.
Scientists were trying to find alternatives to NSAIDs and Cox inhibitors (both pain relievers) since they damage the gut long term.
The focus shifted to anandamide with the following results:
Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447230/
We'll translate.
If you block FAAH (which eats up anandamide), you get more anandamide and gut inflammation and damage go down.
Guess what is a powerful FAAH blocker?
CBD also inhibits FAAH, which results in increased anandamide levels.
https://www.frontiersin.org/articles/10.3389/fphar.2018.00482/full
This effect has powerful results across the body and brain such as with schizophrenia:
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
https://www.nature.com/articles/tp201215
Remember that the endocannabinoid system is tasked with balancing other key systems and anandamide is the backup crew when the primary (2AG) needs support.
PEA is a backup for anandamide and we can directly supplement that (see review here).
Look at its impact:
Fichna et al. showed that lower PEA levels are associated with cramping abdominal pain
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186328/
CBD and PEA together should be powerful allies in gut inflammation and disease.
Let's bring back up TRPV, a key pathway tied to IBD and IBS.
a 2011 pilot study found that ingesting capsaicin-containing enteric-coated pills desensitized TRPV1 and decreased the intensity of abdominal pain and bloating in IBS patients vs. placebo
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186328/
So...we want to turn down TRPV.
CBD has the same effect as capsaicin (the chemical that gives chili peppers their kick):
These data suggest that this expression system is reporting TRPV1 currents which are responsive to both Capsaicin and cannabinoids such as CBD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557596/
So, pain and bloating.
What about motility..constipation and diarrhea?
First, understand that the endocannabinoid system governs all aspects of the gut:
Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130148/
First constipation:
GPR55, another potential cannabinoid receptor, seems to be also implicated in gut motility. Its inhibition reduce motility in mice and this effect was reversed by cannabidiol (CBD), but not by CB1 or CB2 receptor antagonists
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186328/
Okay...so CBD helped to move things along.
And diarrhea:
In the first, the evidence is presented that the endogenous cannabinoid, anandamide, exerts an antidiarrheal action in mice treated with oral cholera toxin (CT) to induce secretory diarrhea
https://www.gastrojournal.org/article/S0016-5085(03)01134-X/pdf
Remember that CBD boosts anandamide.
The GPR55 is an interesting target for IBD and IBS.
In the gut, GPR55 acts like an inflammatory beacon on the lookout for bacteria and potential threats.
People with IBD have been shown to have higher activation of GPR55.
the behavior of GPR55 resembles that of the CB2 receptor which is also increased in inflammatory conditions, such as IBD [32] and which modulates motor functions only in an inflammatory state
https://www.sciencedirect.com/science/article/pii/S1471489212001786
This is important...GPR55 takes over during states of inflammation such as with IBD.
From above, we know that CBD slows down GPR55 activity (antagonist).
We're still waiting for good studies on CBD at high enough doses without the effect of THC.
As for animal studies (they have the same plumbing)...
CBD and chemically induced colitis in mice:
CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis.
https://pubmed.ncbi.nlm.nih.gov/27757083/
The net effect??
In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation.
Motility is short for constipation/diarrhea spectrum.
Another study with different setups:
Cannabidiol reduced colon injury, inducible iNOS (but not cyclooxygenase-2) expression, and interleukin-1.beta., interleukin-10, and endocannabinoid changes associated with 2,4,6-dinitrobenzene sulfonic acid administration.
Okay...that gets technical fast.
Essentially, CBD reduced injury to the colon, dropped inflammatory agents, increased anti-inflammatory agents.
We'll add trials as they become available.
Make sure to check out our CBD and leaky gut and CBD and gut inflammation for more detail.
Before other practical questions, let's look at Vitamin D and other tools.
How does Vitamin D affect IBD plus other tools?
Vitamin D is probably the single biggest and simplest tool we could use to improve health. Point.
Roughly 50% of the population is deficient and that goes by the out-dated 30 ng/ml level which is targeting rickets and bendy knees...diseases we no longer face!
Endocrinologist want us at 60-80. See the full Vitamin D review here.
The key takeaway for IBD is this…
Vitamin D directly governs our immune response and gut integrity!
vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D) has been shown to regulate gastrointestinal microbiota function, and promote anti-inflammatory, tolerogenic immune responses.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566188/
- Gut microbiome. Check
- Reduce inflammation. Check
- Autoimmune suppression (the tolerogenic piece). Check
This is the hail Mary of IBD protection.
African Americans are 80% deficient. Latino's about 70%.
See the pattern...skin color which filters UV light...the source of Vitamin D.
That also speaks to the original risk factors (cold climates, etc).
As for levels in people with IBD:
up to 60% to 70% of people with IBD have insufficient vitamin D levels.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114499/
And that's based on the low 30 levels for rickets!
It's important to test your levels and supplement as needed.
Other tools that may be useful:
- PEA - is safe version of THC in terms of the immune response
- Berberine - helps support the gut mucus protection layer and more
- NAC -reduces oxidative stress
Keep in mind that a strong gut integrity is key to preventing autoimmune (see CBD and autoimmune).
Practical questions now.
How much CBD for IBD
We don't have great research on this yet.
There some studies where 10-50mg helped with the quality of life but did not directly affect the parameters for IBD.
We know that peak neurogenesis is around 300 mg, after which, other pathways kick in.
Based on this, our estimation is between 100-300 mg daily for gut inflammation and support.
Everyone's system is different so test where you get relief.
Keep in mind that any addition of a new player (CBD in this case) may alter the GI microbiome so a few days of "adjustment" is not unexpected although many people report benefits right away.
That brings up an important point...the type of CBD matters.
Let's go there.
What's the best CBD for IBD and IBS
First, we need a very clean product.
- Organically grown in the US at FDA registered farms
- 3rd party tested
- CO2 processed
- No THC
- No solvents
- No heavy metals
- No pesticides
- No mold
Remember, the goal is less gut inflammation and we know from above that outside chemicals are part of the problem.
The bigger issue beyond this is CBD isolate versus full spectrum.
All the research is on CBD isolate but much of the market is pushing full spectrum.
Many people have bad GI responses to full-spectrum due to all the plant material.
Roughly 40-60% of the population has histamine issues and as you recall, very new research is pointing to histamine release as THE trigger for IBS.
The last thing we want to do is cause this effect with plant material.
This histamine response increases as we get older (vitamin D response goes down) and for women (progesterone goes down).
You can see the responses in our product reviews.
We originally tried 3-4 of the biggest brands and had GI side-effects that went away with Isolate.
Then there's cost.
If we're looking at 100-300mg daily, a bottle of 250mg total is useless.
In terms of cost, the key is the price per mg of CBD.
We price our 6000mg bottles at 2-3 cents per mg before discounts up to 30%.
Our founder discovered CBD during a brutal perimenopause so we want to make sure it's available to everyone.
Be well. Take care of each other. Take care of yourself.
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.