Is CBD A Natural Mast Cell Stabilizer?
March 10, 2022
Histamine is finally getting the respect it deserves.
As part of our inflammatory or immune response, histamine research is catching up to a range of issues…especially in our two brains, the gut, and mental health.
Histamine is excitatory in the brain (see histamine and insomnia) and by countering GABA (brain's "brake" pedal), a range of issues can arise when it's set off.
"Released" is the better term and the cells in play are mast cells.
Interestingly, there are natural substances that DON'T build tolerance (so important) that we can use to calm mast cell release of not only histamines but a range of inflammatory cytokines.
We'll go through all of these with the following sections:
- A quick intro to mast cells and histamine
- Why is your inflammatory state ramped up?
- CBD as a mast cell stabilizer
- Other safe tools to stabilize mast cells and histamine release
- How much CBD to stabilize mast cells
- What's the best CBD to stabilize mast cells (very important)
Let's get started!
A quick intro to mast cells and histamine
Mast cells are fascinating. Floating Trojan Horses ready to release their cargo of inflammatory agents.
Histamine is the famous one but many cytokines can be unleashed.
The role of the mast cell is simple. Take cues of foreign invaders (bacteria, viruses, chemicals, etc) and swarm them with histamine which drives pathways to get those outsiders back outside of us as fast as possible.
Sneezing. Itchiness (to elicit scratch), Diarrhea, etc. All roads out of the body!
Fast!
We covered more on this in our CBD and mast cells or CBD and allergies.
This is the proper function but the issue is when the entire system is hyperactivated.
A range of issues can result from mast cell activation (when it releases its cargo) running too high.
We all know the tell-tale signs of mast cell activation - sneezing, itching, coughing, etc.
The real fascinating piece is what histamine does in the brain and nervous system!
It's excitatory! In fact, histamine opposes GABA (brain's brake pedal) for the sleep wake cycle.
You need a range bound level of histamine to stay awake, alert, and engaged.
Range bound being the key term.
We looked at whether histamine is the (or a) key to insomnia.
Just look at the side effects of anti-histamines. Drowsiness. Sedation.
GABA is the same pathway (but opposite histamine) for a range of mental health issues including anxiety, panic attacks, OCD, and more. Pain figures strongly as well.
Too much histamine eats up GABA and that means glutamate (gas pedal) has free-run.
Glutamate is toxic when levels get too high and we have powerful systems to keep it at bay but GABA is the primary inhibitory push-back in the brain and nervous system.
Check out reviews on GABA, glutamate, and even histamine to learn more.
So…why might a person's mast cell pathway be heightened? This is the key question.
Why is your inflammatory state ramped up?
First, understand that mast cells are just a facet of our immune response.
A first-line defense if you will.
The new research on why this might occur is fascinating.
Some usual suspects:
- Early trauma or infection (even in utero) - see early trauma and mental health
- Chronic stress - see CBD and stress
- Gut dysbiosis - gut runs the inflammation thermometer for the rest of the body
- Genetics
- Loss of steroidal hormones (ding ding ding!!)
The early trauma piece is the most exciting.
Essentially, trauma (including psychological, physical, or infection) can upregulate our immune response and inflammation.
It also downregulates key pathways like GABA, serotonin, and more. The natural stress and immune response buffers.
More importantly, it exhausts our balancing system, the endocannabinoid system (more on this later).
The other bookend, steroidal hormones is really where we want to focus.
Mast cell issues hit women disproportionately. The risk also goes up with time as does autoimmune, anxiety/depression risks, and more.
This all makes sense once you understand progesterone's role.
Progesterone is a powerful calming agent on the immune response pathway. For good reason.
Progesterone peaks during pregnancy to protect the amniotic sac from being attacked by the mother's immune system. The sac is actually made from the father's DNA…a "foreign" entity if you will.
If progesterone levels are low, the mother's immune system will attack the amniotic sac.
Goodness. The connection with premature birth and even early loss:
Progesterone administered via the vagina may reduce the risk of preterm birth in women who are at risk of giving birth early when compared to a placebo, treatment as usual or no intervention.
This is now pretty well known.
Here's the problem. Progesterone in women is at 50% by age 40. Men's levels drop as they age as well.
When do histamine problems creep up?
During the 40's. Same with autoimmune.
Check our review on progesterone here. It's a powerful player in the mast cell pathway. We even dive into progesterone and histamine directly.
For a clincher:
These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.
https://pubmed.ncbi.nlm.nih.gov/17166400/
Has to be bio-identical and oral absorbs more readily.
So…trauma, stress, and loss of hormones. All big players. Let's look at what we can do about it.
We'll start with CBD.
CBD as a mast cell stabilizer
Our endocannabinoid is tasked with balancing other key systems:
- Endocrine - hormones like cortisol (stress response) and steroidal hormones.
- Immune - inflammation including mast cels
- Nervous system - neurotransmitters like GABA, serotonin, and more
Anandamide is the power player in this system and it's named after the Hindu goddess of "bliss".
Anandamide acts like a big wet blanket on stress, inflammation, and other ramped-up states to bring them into balance.
The connection between this system and mast cells is direct and powerful:
we show that normal skin MCs are tightly controlled by the endocannabinoid system.
https://www.jacionline.org/article/S0091-6749(11)01796-9/fulltext
And more importantly:
This limits excessive activation and maturation of MCs from resident progenitors via “tonic” CB1 stimulation by locally synthesized endocannabinoids.
Translation…if mast cells are hyperactivated, zero in on the endocannabinoid system…it's under duress.
We looked at endocannabinoid deficiency but let's turn to CBD.
We don't want to just pump up anandamide directly. THC mimics anandamide but it pushes too hard and lasts too long.
As a result, the body will push back and actually ramp up natural mast cell activation.
This is tolerance…the enemy for any kind of intervention.
Instead, CBD reduces FAAH, the substance that breaks down anandamide.
This allows anandamide, which normally gets created and broken down very quickly, to linger a bit more.
No tolerance!
We see this across powerful pathways like serotonin, GABA, and immune response.
For example:
- Healthy cell with low inflammation - CBD has no effect
- Healthy cell with high inflammation - CBD reduces inflammation
- Cancerous or virally infected cell - CBD INCREASES inflammation
Three different responses depending on the state of the system.
The third one makes sense once you know that the immune system kills off cancer by jacking up inflammation (oxidative stress technically).
Back to mast cells. So CBD supports the calming effects of anandamide but as a feedback mechanism (not just up up up).
This is incredibly important.
Let's zero in on CBD and mast cells directly.
There are two key pathways to look at with CBD and mast cells:
- MDSC - myeloid derived suppressor cells
- PPAR - a key suppressor of mast cells and inflammation
MDSC's basically counter mast cells. The opposing force. They are immunosuppressive.
PPAR calms mast cells as well:
The inhibitory effects of PPAR γ agonists include suppression of the activation of mast cells and a decrease in mast cell function in the inflammatory response. Therefore, PPAR γ agonists may serve as effective anti-inflammatory reagents in the treatment of allergic reactions.
https://pubmed.ncbi.nlm.nih.gov/28656266/
Sorry for going into the weeds but it's important to find real research to back any supplement.
So…back to CBD.
A study zeroed in on CBD's impact on both in heightened states of inflammation and mast cell activation:
Together, the results suggest that CBD may induce activation of PPARγ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433789/
So..more PPAR and mobilization of MDSCs which "resolve" mast cell activation. Again, we don't see this in healthy states where mast cells are functioning correctly.
Let's turn to the gut (the key thermostat for system-wide inflammatory states)!
A study looked at colitis tissue and mice guts that were inflamed with bacterial signatures (LPS).
The results:
Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190/
So…across all markers, a calming of histamine response.
We would expect to see downstream results on issues tied directly to mast cell activation such as asthma.
The results:
There was a significant and inverse correlation between CB1 levels and lung function in asthmatic patients. CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma.
https://pubmed.ncbi.nlm.nih.gov/30481497/
CB1 is the receptor that anandamide plugs into (and THC mimics).
The skin is a great canary in the coal mine for mast cell activation.
We can directly touch it!
Dermatitis is the official term…allergic skin irritation.
This will get technical but we'll break it down:
We show that in poly-(I:C)-stimulated HaCaT cells, CBD elevates the levels of AEA and dose-dependently inhibits poly-(I:C)-induced release of MCP-2, interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α in a manner reversed by CB2 and TRPV1 antagonists 6-iodopravadoline (AM630) and 5'-iodio-resiniferatoxin (I-RTX), respectively, with no cytotoxic effect.
https://pubmed.ncbi.nlm.nih.gov/29632236/
Translation, after a skin allergic reaction is set off, CBD boosted levels of anandamide ("bliss" molecule from above) and reduced a slew of inflammatory players…with no ill effects to the cells.
When they blocked CB2 (a type of receptor prominent in the immune system) and TRPV1 activity, CBD lost its effect.
Essentially, CBD helps modulate the immune system response to calm mast cell activation with TRPV being an additional pathway.
That's the beauty of the endocannabinoid system…it's about balance with many different pathways affected.
We have a huge review of CBD and PEA (discount THC without the high) for mast cell activation with lots of research.
The type of CBD used is critical and we'll cover that below.
First, a few more tools (because we're all about research whether CBD or not).
Other safe tools to stabilize mast cells and histamine release
The body has key buffers to histamine and immune hyperactivation.
These are key players to get to the root of why mast cells may be out of balance:
We have big reviews on each of these but a quick snippet.
Magnesium glycinate and mast cell stabilization
Mag is a key stress buffer and calming agent across multiple pathways including inflammation!
The results of mag deficiency:
many investigators have recognized the same symptoms in relation to degranulation of mast cells with a release of histamine and inflammatory mediators
https://www.sciencedirect.com/science/article/pii/S0925443900000181
Just reducing mag can cause mast cells to populate:
In both males and females fed the Mg-deficient diet, the marrow mast cells increased five to six times, while their number was concomitantly decreased in the skin.
https://academic.oup.com/jn/article-abstract/107/12/2164/4768984
The "ates" cross the blood brain barrier best. Magnesium glycinate is great and it combines glycine which is also inhibitory (like GABA).
See review on magnesium glycinate.
Mag is very safe…I take 3-4 at 100mg daily to avoid migraines (GABA exhausted).
PEA mast cell stabilization
PEA is a backup to anandamide with no high effect. This is important because the "high" indicates too much activity at CB1 receptors (like THC) which causes tolerance.
A key role of PEA may be to maintain cellular homeostasis when faced with external stressors provoking, for example, inflammation: PEA is produced and hydrolyzed by microglia, it downmodulates mast cell activation,
https://pubmed.ncbi.nlm.nih.gov/23813098/
We have a huge review on PEA.
Vitamin D mast cell stabilization
Get tested. Try to get your levels above 50ng/ml.
Vitamin D is a master regulator of the immune system and it goes down as we get older.
So many people are deficient (roughly 50% and higher depending on skin color).
D is a monster player in mast cell stabilization:
vitamin D3 metabolites suppressed IgE-induced mast cell-derived pro-inflammatory and vasodilatory mediator production in a VDR-dependent manner in vitro.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154631/
We have a giant review on Vitamin D since it's so important.
Berberine mast cell stabilization
All immune roads lead to the gut and berberine is a powerful player there.
This includes mast cells:
The above results indicate berberine could suppress mast cell activation and allergic responses.
https://pubmed.ncbi.nlm.nih.gov/30861392/
Big review on berberine berberine.
Finally, the big player (for women).
Progesterone mast cell stabilization
Progesterone drops by 50% at age 40. All the risks creep up from there (autoimmune, histamine issues, etc).
We discovered CBD from a brutal perimenopause (that story is here).
Progesterone's role in the body is to calm the immune response for pregnancy since amniotic sac is essentially from father's DNA (foreign entity).
Simply put:
These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.
https://pubmed.ncbi.nlm.nih.gov/17166400/
Steroidal hormones are front and center if low. Testosterone is actually immune balancing for men!
A few notes…some of these are fast (magnesium, PEA) while others build up (berberine, Vitamin D).
CBD has both a fast and slow effect.
Let's look at practical questions.
How much CBD to stabilize mast cells
A wellness dosage is about 50mg daily. Peak neurogenesis is around 300mg daily.
Research on sleep is in between at 160mg. That's a good marker since histamine is such a disrupter or sleep.
In fact, histamine may be the key to insomnia.
So we have a range of 50-300mg. You can break it up into small doses since the peak blood levels of CBD is about 4-6 hours.
Holding under your tongue up to 60 seconds can boost availability and taking after meals also help.
Adjust according to how you feel.
Many people will start higher to get their immune system back in balance and then reduce later.
The first 10 days may be 300mg and then 100mg daily after that.
Berberine, Vitamin D, progesterone, etc take about 3 months to really integrate.
The type of CBD is super important.
What's the best CBD to stabilize mast cells (very important)
First, we don't want to trigger further histamine issues:
Our testing is available at the top of each page.
The bigger issue we see is CBD isolate versus full spectrum (which is pushed everywhere).
Read our reviews…the side effect profile between isolate and full spectrum is night and day!
The plant material and/or small amounts of THC are anathema to anyone with histamine issues.
All the research is on CBD by itself…isolate!
This is the BIGGEST issue with CBD on the market but especially for mast cell issues.
We have a review on full specturm versus isolate for histamine.
Finally, there's cost.
We price our 6000mg bottles (30 doses x 200mg) at 2-3 cents per mg BEFORE discounts up to 50%.
We discovered CBD from a brutal perimenopause with rampant mast cell activation issues. Couldn't eat most foods. Could not wear any cosmetics or use many skin products.
Racing heart, rolling panic attacks, and insomnia.
Finally stumbled on CBD isolate and that's why we do what we do now.
Be well. Take care of each other. Take care of yourself.
Reach out to us with any questions you have via the chat buttom. We love putting together targeted research for your situation.
Related Research:
Does histamine drive insomnia
Progesterone and histamine
Top 10 Tips for calming mast cells
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.