CBD and MCAS Explained

CBD and MCAS explained

We're writing this big review somewhat out of self-interest.

Of all the reasons that people try CBD isolate, MCAS appears to have best results!

Anxiety, sleep, pain, and mental health generally all appear in NIH studies but just look at the reviews (here) from actual people here!

We've done deep dives on CBD and histamine (a product of those mast cells) and even CBD and the immune system (both too hot or too cold).

Let's zero in on CBD and MCAS more specifically with these topics:

  • A quick intro to MCAS and it's many drivers
  • What is driving MCAS
  • CBD isolate's role in the immune system
  • CBD and MCAS research
  • Why the type of CBD matters so much for for MCAS
  • How much CBD for MCAS


Let's get started.  We're going to cover quite a bit and branch out to other review for break-out information.

If you want a deeper dive with LOTS of NIH research, check out our guide on CBD and its cousin PEA for mast cells.

To the mast cells shall we!

A quick intro to MCAS and it's many drivers

MCAS is short for Mast Cell Activation Syndrome.  Different from MCAD or Mast Cell Activation Disorder.

One involves too much activity or sensitivity while the other involves too many actual mast cells.

We'll use them interchangeably.

The key is to understand the role of the mast cell especially in today's environment (translated…dirty and hostile).

Mast cells are really part of the immune system.  Think of them as forward guards out in world there to respond to foreign intruders:

  • Bacteria
  • Mold
  • Viruses
  • Chemicals
  • Poisons

Anything that might hurt us!

Mast cells are roaming arsenals of immune agents just waiting to respond on a hair-trigger notice.

If the immune system notifies them for action due to some hostile interloper, they release their weapons in response.

The primary arsenal:

  • Histamine - a powerful allergic response agent
  • Cytokines - inflammatories assassins
  • Heparin - anticoagulant to cause more flow
  • Growth factors - repair agents for after the assault


The big one we're all familiar with from allergic reactions is histamine.

Huge review on histamine here which also happens to be a powerful neurotransmitter in the brain (think insomnia, anxiety, repetitive thoughts and more).

The relationship between histamine and GABA (sleep, pain, and anxiety) or histamine and serotonin (mood, feeling grounded, stress response) is utterly fascinating and we'll cover this below.

It's not just about itchiness!

Our main focus will be on histamine here since it's primary payload of mast cells that drive so much suffering.

The cytokines are a close second though as they're the driver of inflammation.  

That's pain, redness, mental health issues, gut issues, etc.

Longer term, this is real damage.

So…what is MCAS?

Quite simply, our mast cells are hyperactivated.  

Either they are coming into contact with foreign entities that they should actually be responding too but they are overwhelmed (we'll get to this below)


The mast cells are over-reacting which is classic allergic response behavior just much more severe and constant.

Either way, it's an imbalance (make a note next to that word for CBD) in our immune's response to its environment.

That's our body's response.  Let's look at what is driving it.

What is driving MCAS

It's always nurture or nature!  Generally it's a mixture of both.

The nature side is easy in that genes don't change too much but clearly MCAS has tracked all the other allergic conditions with a trajectory that is up up up over the past decades.

MCAS is really a newer umbrella term for overactive immune response since 2010 but it's clearly prevalent:

Mast cell activation syndrome (MCAS) is an immune disease with an estimated prevalence of 17%.


Let's look at clues around allergic reactions (a function of mast cells) to see if there are any trends.


First, food allergies:



What about auto-immune, a situation where the immune system has been incorrectly targeted to our own tissue:


Of course, autoimmune hits women 8:1 and we go in why loss of progesterone is such a huge player at our CBD and auto-immune.


This makes sense once you understand that progesterone protects the amniotic sac from mother's immune system since it's actually made with father's DNA (so technically, a foreign entity).

Learn more about progesterone here.


Progesterone is a powerful calming agent on the immune system including mast cells!

Mother nature designed it this way to protect the amniotic sac from the immune system since it's actually made with dad's DNA (essentially foreign!).

Progesterone drops by 50% by age 40 and continues down from here leading to a huge swell in all things immune including…mast cells!

Clearly, something is driving the increase in how our immune system including mast cells is reacting.

What are the probable causes.

Goodness…do you have a minute!

We've looked at many of these in detail but a quick synopsis:

  • Pesticides and food additives
  • Hormone mimickers in food, cosmetics, and skin products
  • PFOA and other industrial chemicals
  • Microplastics and plastics in general
  • Reduction in key minerals and nutrients (Vitamin D being a big one)
  • Interaction with different viruses and infections
  • Trauma and chronic stress


Any of those foot the bill for you?  Thought so.

We are swimming in a sea of mast cell triggers so it's no wonder that MCAS literally became a new diagnosis.

We wouldn't be surprised especially after the most recent "immune" situation if MCAS tracks the upward increase of obesity and diabetes over the next decade or so.

Makes perfect sense.  Check out our CBD and gut inflammation to dig into some of this.

We could (and will) spend an entire article on the the "why" of MCAS.  Let's turn to a potential tool.

A pitstop first to the endocannabinoid system.

CBD isolate's role in the immune system

Is the whole CBD buzz just good marketing?  Is there an actual scientific basis for it's role in MCAS?

Glad you asked.

CBD works by supporting our endocannabinoid system when running low.  That's why it doesn't build tolerance like THC or other cannabinoids.

Essentially, it works like a feedback mechanism…technically called an allosteric positive modulator.

This tolerance piece is so important since most tools/medications will cause the body to push back so your natural pathway gets weaker with time.

The endocannabinoid system is is fascinating.

It's tasked with balancing other key systems in the body when they're pushed one way or another:

  • Nervous system - including neurotransmitters like serotonin, GABA, and more
  • Endocrine system - hormones both steroidal and metabolic
  • Immune system - DING DING DING.  Cytokines, histamines, and mast cells!

The latter one is our focus here.  

Here's how it should work.

Our body comes in contact with a foreign agitator.  Maybe bacteria.  Maybe pollen or a bee sting. Maybe BPA from a can lining.  Or a food coloring.  Or estrogen mimicking chemical.  Or Red #40.  You get the picture.

The mast cells are called into action to get this potential bad actor OUT of the body fast.

It releases it's arsenal of histamine and inflammatory agents as a result.

The invader is neutralized (hence all your coughing, sneezing, diarhrea, skin itching, etc).

Now, the body can't just keep responding this way.  The mast cells must calm back down.  Inflammation needs to resolve.

Hello endocannabinoid system!

This system is all about bringing key systems like mast cells and immune back to baseline.

Simply put:

Endocannabinoids are believed to control immune functions and play a role in immune homeostasis.



Homeostasis just means…balance.


And more importantly to our discussion:

Endocannabinoids limit excessive mast cell maturation and activation in human skin


MCAS is a state of imbalance where the immune system (i.e. mast cells) are on high alert.  Constantly.

You might argue that MCAS is really a disease of endocannabinoid dysfunction.  We looked at whether modern diseases reflect the ECS not keeping up with our modern world.

MCAS is just a very noticeable effect from this.

We'll leave our CBD and the immune system review for more detail but let's dive directly into MCAS directly.

CBD and MCAS research

Here's the beauty of CBD (and really the endocannabinoid system it supports)...

It's effect depend on the state of the system.


Cancer (see CBD and cancer) is a perfect example of this:

  • Normal cell with low inflammation:  CBD has no effect
  • Normal cell with high inflammation : CBD reduces inflammation
  • Cancerous or virally-infected cell:  CBD with SPIKE inflammation

Read that back over.  It's fantastic from our view.


The third outcome makes sense once you know that the immune system naturally kills off faulty cells by boosting inflammation (cell suicide…called autophagy) with oxidative stress (a form of inflammation).

3 states.  3 different outcomes.  All ones we want!


THC, CBD's cousin in the hemp plant is always suppressive which isn't great longer term for health.  We want flexibility.

So…CBD generally calms inflammation.  What about MCAS?

This may be our favorite part and why so many people see pretty impressive results (see the reviews).

We need to introduce your new best friend, MDSC.

MDSC is short for Myeloid-derived suppressor cells.

Simply put…they're the clean-up crew that comes in to calm down mast cell activation!

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of myeloid cells that are believed to be arrested at an immature state of cell differentiation, meanwhile acquiring potent immunosuppressive function



"Potent immunosuppressive function".

You could argue that mast cells and MDSC are opposing factors in allergic responses.


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

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



Let's translate please.

CBD interacted with a powerful anti-inflammatory pathway called PPARy to kickstart the mast-cell calming response (MCSD).  

Interestingly, CBD does not do this states of low inflammation or mast cell response.


Another study looked at CBD and pain resulting from mast cell hyperactivation (mastocytosis).

The mean ± standard deviation NRS pain score decreased significantly from 7.27 ± 1.35 before treatment to 3.78 ± 1.99 after 3 months of treatment (p < 0.0001). Fifteen patients (34%) were able to discontinue all their previous antalgic medications.



Mast cells also release prostaglandins, a key pain signalling agent (see CBD and pain).


Some animal studies are finally getting to actual question of CBD and mast cell activation such as this one:

The intraperitoneal administration of CBD suppressed passive cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and decrease in the number of degranulated mast cells.



"Degranunated" just means that the mast cells have spilled out their content (histamine, cytokines, etc).   So less of that.

Net net…

CBD suppressed antigen-stimulated mast cell degranulation in a concentration-dependent manner.

Antigen is the triggering chemical.  Concentration-dependent matters since it establishes a cause-effect relationship (not just something else).

Let's look at some of the common symptoms and related issues tied to mast cell activation.

CBD, mast cells, and asthma

Mast cells are a key factor in the development of asthma, contributing to both the early and late phases of the disease.  

So…(see CBD and asthma):

CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma.


What about CBD and mast cell driven skin irritation:

The anti-inflammatory effect of CBD is demonstrated in several experimental studies and clinical studies. In an in vitro model of allergic contact dermatitis, CBD demonstrated dose-dependent inhibition of monocyte chemotactic protein 2, which attracts mast cells and macrophages to inflammatory sites, and other pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α.



Translation please.

CBD calms the upstream pathway that causes mast cells to congregate and release.


More importantly to us as sufferers:

An observational study demonstrated that the topical application of CBD gel reduced a patient-oriented eczema measurement score from 16 to 8.1 (p < 0.001)



Wow…dropping the perceived skin irritation in half!

One final stop…the gut.

Most of our immune response actually resides and initiates in the gut.  See CBD and gut inflammation.

Via the vagus nerve, this transmits up to the brain and we see lots of mental health results from MCAS and resulting inflammation.

Don't get us started on histamine (anxiety, insomnia, pain, depression).

What about CBD and gut inflammation?

In the tissue sections of LPS-treated mice and receiving CBD treatment a significant reduction in mast cell number was observed.

What about CBD and all the inflammatory milieu that spills from mast cells?


Look at CBD and the inflammatory agents 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



IL-10?  Oh it's just one of the remediating (calming) cytokines which we want more of.

Again, tons of NIH studies here on CBD and mast cell activation.

Let's now turn to an important point regarding the type of CBD and MCAS.

Why the type of CBD matters so much for for MCAS

All types of CBD are not the same!

All the research we've seen is on CBD isolate.  CBD by itself.

Full or broad spectrum CBD is likely to cause a mess for people with MCAS.

All that plant material and other cannabinoids can (and probably will) trigger the histamine response we're trying to calm down.

The results we see in reviews are night and day between CBD isolate and full or broad spectrum.

THC is suppressive of mast cells but it builds tolerance which means that our own natural calming pathways will be further whittled down.  This is not a long term solution.  See CBD versus THC for more info.

Interestingly, 75% of people with histamine issues are allergic to THC (estimate at about 30% of the population).

Finally, the quality of CBD is critical especially for systems sensitive to toxins and chemicals.

It must have:

  • From organically grown hemp in the USA at FDA registered farms
  • 3rd party tested for the following:
  • No THC
  • No mold
  • No pesticides
  • No heavy metals
  • No solvents
  • No bacteria


We test all of our CBD along these lines since we tried 3-4 of the biggest brands when we first started and had the tell-tale gut issues and other histamine responses.

Again, look at the reviews and sort by mast cell or MCAS to see the results!

What about dosage?

How much CBD for MCAS

We treat this like our research for drug withdrawals.

  • The first 10 days are generally the toughest and require a higher amount.  
  • Day 11 to 30 carries us out to where our epigenetics changes to reflect the new inflammatory status.
  • Month 2 and beyond depend on how you feel and what the lowest amount you can take.

So a potential schedule (adjust according to how you feel):

  • Day 1-10:  600-800mg daily to provide relief and calm system
  • Day 10-30:  300mg which reflects max neurogenesis; a sign of peak response
  • Day 31+:  100mg??  Depends on how you feel

Hold the CBD under your tongue up to 60 seconds to boost bioavailability which can help you save on CBD cost (by using less).

We also look at other tools for MCAS that don't build tolerance and can support CBD.

mast cell activation tools


Reach out with any questions and be well!  

Mast Cells are the canary in the immune system coal mine with all the other aspects of inflammation tied to mental health, aging, the whole spectrum of IBD/IBS and every other aspect.

Calming mast cells is an initial sign that we're making ground.

More to learn:



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