CBD Research  -  How CBD Works with Mast Cells



Most people have never heard of "mast cells".


Outside of biology class and even there, it's a fleeting conversation.


If the term mast cell is in your repertoire then you've had to learn about it out of necessity.


Survival really.


It's the linchpin for all things allergies and histamines.

Everything ranging from simple sneezing to a friend's pet to much more serious reactions including asthma and MACD (mast cell activation disorder).


This is where the body's immune response goes haywire.


The immune system is turning out to be the most beautiful, complicated, and if it goes wrong...frustrating system in the body.


It's at the heart of many new discoveries into disease and pathology.


We've written extensively on CBD and the gutCBD and the immune system, and CBD and allergies separately.


Let's narrow the focus down to the histamine pathway.


We'll assume you already know about DAO and how to supplement it.


Let's take for granted that you're avoiding histamine-high foods and histamine releases


What about CBD?

It's showing much promise with other aspects of the immune system.


What about CBD and mast cell activation?


There's interesting research there and we expect much more soon.


You can jump to any of these sections here:



Let's get started.


It's spring somewhere!



For deeper dives after this review


Top 10 tips for calming Mast Cells

Is CBD a natural mast cell stabilizer

CBD and PEA for Mast Cell Stabilization

Is Progesterone key to mast cell activation?



Quick Introduction To Mast Cell Activation

Mast cells were discovered in 1878 and got their name for the German word for "overfed".


This is due to the packed visual of granules within the cell.


These so-called granules are packed with histamine, heparin, and various other inflammatory and repair chemicals.


The big one is histamine in terms of allergic responses and mast cell activation.


Mast cells are an important part of our innate and adaptive immune system.


They are created in our bone marrow and move around the body to sites where they are prevalent:

  • Mucous linings
  • Airways
  • Vascular system


Interestingly, they're also in charge of vascular dilation (constriction and opening of veins and arteries) and peristalsis (movement within the bowel).

This ties into their ability to respond to foreign intruders.


Get them out!


The mast cells main responsibility is to look out for potential bad actors in the body and get them out of the body as fast as possible.


They're a first responder of sorts which is why you find them everywhere the body comes in contact with the outside world.

  • GI tract
  • Skin
  • Airways


They not only work to fight off potential bad actors, but they're also involved in the repair process of damaged tissue.


Inflammation gets a bad rap but within normal ranges and for discreet periods of time, it's actually incredibly important to repairing and rebuilding tissue.


The issue is when mast cell activation (basically the release of its payload...histamine) goes too far.


This can happen for two main reasons:

  • Too many mast cells are present
  • Mast cells overreact to simple triggers


These are both questions of "balance" or homeostasis (the technical term).


Keep that word tucked away because it's critical to our initial question of CBD and mast cell activation.


You can learn all about CBD and histamines here but we want to focus on mast cell activation.


The triggering of the response itself!


Let's introduce the endocannabinoid system first.

The Endocannabinoid System And Mast Cell Activation

The endocannabinoid system is newer to the medical community.

Actually, they're slow to the game but research has studied it pretty intensively for 20+ years.


We all have one and it's shared with most animals.


It's dated back to about 600 million years so mother nature stumbled on something it liked and kept it.


Insects missed the party (came to early actually).


Here's a quick visual:


How does CBD work in the body


It's primarily tasked with balancing three key systems:

  • Nervous system
  • Immune system
  • Endocrine system

The second one is where we want to focus in terms of mast cell activation.

Really, most modern health issues are pointing back to the immune system being out of balance!


Think of all the auto-immune diseases.


Just watch an RX ad and it's probably autoimmune.


New research is coming out daily!


Just yesterday, a report showed that an industrial enzyme used to process dairy, baked good, and meats might be at the heart of gluten insensitivity:



That was yesterday.


The day before, the immune system as a cause of MS.


It's coming faster by the day!


Mast cell activation disorder is just a component of our immune system with very specific issues and results.


Rather than attacking the joints (arthritis) or the islets cells (diabetes), this system causes an over-reaction of its primary weapons:

  • Mucus creation (which is protective in the body)
  • Inflammation (also protective for short durations)
  • Increased blood pressure and bowel movement (get it OUT!)


Too much of a good thing.


The endocannabinoid system is tasked with balancing this response!


How do we know this?


Research. Always research.

First, are there endocannabinoid receptors on mast cells?



Before we go further, let's introduce the naturally occurring cannabinoids in the system:

  • Anandamide
  • 2-AG
  • PEA


These come up quite a bit in the study of the endocannabinoid system in mast cells and we would hate to start off with confusion!


Back to the studies...


An example of CB (cannabinoid) receptors in play within mast cells

Indeed, this substance has been extensively investigated in mast cells (especially in wild-type rats) that produce high levels of PEA and express both CB1 and CB2


CB1 and CB2 are just the two receptors that cannabinoids interact within the body.

So how do they affect mast cells?

PEA is a strong inhibitor of mast cell degranulation and activation,111 also contributing to reducing the severity of spinal cord trauma


This is a big deal.  PEA, a naturally occurring endocannabinoid, acts as the brake on mast cell activation!


That's great for rats (congrats)...what about humans?

Also, AEA has been shown to inhibit mast cell degranulation in a human mast cell line


AEA is Anandamide...the so-called "bliss" element named after the Hindu goddess of bliss...Ananda.


There's so much in a name!


It's the most prominent, naturally occurring cannabinoid in our body which huge implications for mood, energy, and sleep.


We'll get to how CBD interacts with Anandamide below.


By the way..."degranulation" just means mast cell activation or release of histamines.


Releasing the payload!

Essentially, Anandamide is the brake for mast cell activation (or one of them).


Let's look at the mucus pathway specifically (think nose, throat, and lungs).

AEA and CB1 in modulating human mast cell functions was further confirmed by the observation that in human airway mucosal mast cells, maturation and excessive activation were inhibited by the endocannabinoid tone through CB1 stimulation.


This may get a little technical but bear with us.


AEA was also shown to recruit special cells in the body that turn down the mast cell activation response:

AEA activation of CB1 in mast cells induced monocyte chemotactic protein-1-mediated recruitment of monocytic and anti-inflammatory myeloid-derived suppressor cells


Again, it acts as the brake to calm the response if excessive.



There's also the issue of having too many mast cells.


Over proliferation!


The endocannabinoid system controls this as well!

Endocannabinoids limit excessive mast cell maturation and activation in human skin.



That's the other side of the mast cell activation coin.


To summarize FROM the research...

The generally immunosuppressive role of classical eCBs (AEA and 2-AG) on the different immune cell populations is abundant compared with their congeners (PEA) and is reasonably equivalent in both mice and humans, making them "master regulators" of the innate-adaptive immune axis.


We left with this for a simple reason.


The endocannabinoid system is marbled within many systems and pathways that are all intertwined with mast cell activation.


Basophils. T cell, Cytokines.


It's a veritable biochem alphabet soup!


The key words above are "master regulators".


Mast cells are incredibly important to our good health.


When they're response is excessive, they can be incredibly suspect to many diseases.


It's the "over-reaction" that we want to address and the endocannabinoid system is tasked with balancing this response.


After 100's of hours of research, it appears to us that the endocannabinoid system is the one that bears the burden of modern lifestyle.


As we mentioned above, an industrial enzyme used in the processing of dairy, baked goods, and meats may be the trigger for gluten insensitivity.



This is the latest addition regarding thousands of chemicals in our food and surrounding products.


The endocannabinoid system is trying to juggle plates while standing on a merry-go-round.


Let's see if CBD might help.

CBD And Mast Cell Activation Based On Research

Clearly, the endocannabinoid system is integral to healthy mast cell activation.


And it's under duress!


Can CBD help?


First, understand that CBD and cannabinoids, in general, are generally deemed "as needed" in function.


This means that the body has a specific level of these different substances it needs to function.


If it gets low, outside cannabinoids like CBD can fill the gaps.


If it's not low, it doesn't use the CBD.


We mentioned Anandamide up above and its role of dialing back excessive mast cell activation...


There's a direct connection between CBD and Anandamide:

As an example, CBD has been shown to bolster anandamide when running low.



We discussed how Anandamide helps to calm the mast cell activation and CBD boosts it's effect when needed.


Let's look at the research.


Some of this may get down in the biochem weeds but we'll trim around the edges so we can see what's going on!



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



What in the heck does this mean?


Translation, please.


PPAR is a mast cell brake. It's turned down the response.


Every system in the body has both a gas pedal and a brake pedal.

  • PPAR is a chemical brake.
  • MDSC is another immune system brake.


We want that when excessive.


Let's look at the heart of our immune response including mast cells...

The gut!

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



Furthermore.... (love the part of about reduced damage!!)

These actions lead to a reduction of intestinal damage mediated by PPAR gamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.


Remember that mast cells are integral to maintaining the gut mucous lining that protects us from all sorts of nasty out there!


This figures directly into auto-immune cells where bacteria and foreign entities migrate to other parts of our body only to be attached by our immune system later!


For example, CBD affects this same pathway in the MS and Encephalomyelitis

Cannabidiol Attenuates Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Through Induction of Myeloid-Derived Suppressor Cells



There's that "MDSC" pathway again.


Mast cell activation is a very specific term.


There's lots of research on CBD and all the adjoining areas and topics here:


Before we run out and try CBD, there's a very important note on what type works best for mast cell activation.

Best CBD For Mast Cell Support

It's almost as if the CBD brands and industry have no knowledge of mast cell activation.

Everyone and their mother is literally pushing "full-spectrum" CBD.


It's very frustrating because people with mast cell activation disorder or just histamine issues might have a very different result.


Full-spectrum just means more plant material makes it into the finished product.


That's not great if you have a sensitivity to plant material (cough cough...people with MCAD).

For this reason, we recommend CBD isolate.

CBD isolate is the CBD extract itself which doesn't have a histamine load (and has all the benefits above) with a base oil (usually MCT oil – extract from coconut).


You need the oil as fat to help the CBD get into the body.


CBD isolate is by far the best approach for MACD sufferers to test CBD with.


Again, most brands are pushing full spectrum.


The other issue is that full-spectrum can legally have up to .3% THC.

It's estimated that 70% of people who have allergy/histamine issues will also have reactions to THC!


We want ZERO THC.


For CBD isolate, the best value option which is 3rd party tested for safety is:


IndigoNaturals 2000 CBD Isolate for allergy and  histamine issues Pharma xtract 30 ml 2500mg


Then the question...how much to take?

How Much CBD To Take For Mast Cell Support

Start slow.


25-30 mg test to see how your body responds.


Place it under the tongue for 30-60 seconds for direct absorption.


If you have symptoms from MACD (very likely), you should see the impact relatively quickly.


My wife's sinuses clear up almost instantly!


Again, start slow with high quality, organically grown CBD (CO2 Extracted) that's been tested free of:

  • Heavy metals
  • Pesticides
  • THC
  • Solvents
  • Bacteria
  • Mold

Most of the research is based on 300-600mg of CBD.


Start slow, and work up to see where you get benefits.


Of course, let us know what works for you!


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