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Cannabinoids & Inflammation: Is There a Mast Cell Connection?

Updated: Feb 17

Inflammation, pain, fatigue, skin problems, headaches, migraines, allergies, gastrointestinal symptoms, and brain fog. The list goes on. If you are familiar with these symptoms, you may be dealing with mast cell activation issues. I have shared my top tips on how to stabilize your mast cells in this article. However, I didn’t mention cannabinoids. Yet, research suggests that cannabinoids, like CBD and marijuana, may help to reduce inflammation, pain, and symptoms of mast cell activation. Today, I want to explore the connection between cannabinoids and mast cells. Let’s get into it.

What Are Cannabinoids

Cannabinoids is an umbrella term for a group of chemicals found in the cannabis plant. Though there are over a hundred chemicals in the cannabis plant, there are two main cannabinoids that are commonly used for improving inflammation, pain, health issues, cancer, and other health issues.

The two main cannabinoids include:

  • Cannabidiol (CBD)

  • Tetrahydrocannabinol (THC)

THC is a psychoactive content that is responsible for the ‘high’ of using marijuana. CBD is a compound also derived from hemp, but unlike THC, it doesn’t lead to a ‘high’ feeling.

CBD may be extracted from both hemp and marijuana, which are both plants in the cannabis family. This is important to note because marijuana, as well as CBD extracted from marijuana, are currently not legal in most states in the United States (1, 2). CBD extracted from the hemp plant is legal across the US. In Canada, marijuana and CBD are both legal for recreation and medical use (3). If you live outside of Canada and the US, you need to check with your local government for local laws.

What Is the Endocannabinoid System

The name of the endocannabinoid system (ECS) comes from the word ‘endo’ (short for endogenous) and ‘cannabinoid’. Endogenous means that something is made inside your body. ‘Cannabinoid’ is the term for a cannabis-like substance. Thus, ‘endocannabinoid’ is a term for cannabis-like substances naturally made inside your body.

Your endocannabinoid system is a sophisticated cell-signaling system within your body. The goal of your endocannabinoid system is to create homeostasis, or balance.

Your endocannabinoid system has three parts, including (7):

  • Endocannabinoids

  • Receptors that can bond with both cannabinoids and endocannabinoids

  • Enzymes that can break down cannabinoids and endocannabinoids

What Are Endocannabinoids

Endocannabinoids are lipid (i.e.fat)-based neurotransmitters inside your body. They act as chemical messengers. They help to transport signals between your nerve cells and support various important functions inside your body.

There are two major known endocannabinoids, including:

  • Anandamide (also known as arachidonoyl ethanolamide or AEA)

  • 2-arachidonoylglycerol (also known as 2-AG)

What Are CB1 and CB2 Cannabinoid Receptors

There are two major cannabinoid receptors, CB1 and CB2. They have a critical role in your endocannabinoid system. CB1 is located in your central nervous system, including your cortex, cerebellum, hippocampus, basal ganglia, and nerves of your spinal cord. CB2 is located in your peripheral nervous, digestive, and immune systems. CB1 and CB2 both play an important role in creating healthy inflammation levels, supporting immune functions, supporting digestion and appetite, regulating pain levels, supporting sleep, regulating your mood, and helping other bodily functions.

What Enzymes Break Down Endocannabinoids

The function of endocannabinoids is to create homeostasis. Once they’ve done their job, there is no need for them. This is when certain enzymes can come into play to break them down and prevent the buildup of excess endocannabinoids. Two major enzymes help to break down endocannabinoids: fatty acid amide hydrolase (FAAH) and monoacylglycerol acid lipase.

Homeostasis and Your Endocannabinoid System

The endocannabinoid system can trigger many mechanisms inside your body to maintain homeostasis (5). A 2018 review published in the International Journal of Molecular Sciences has found that it may help to regulate inflammation levels, pain sensation, immune responses, digestion, metabolism, learning, memory, mood, and reproduction (6). According to a 2019 review published in Acta Pharmacologica Sinica, endocannabinoids may serve as a therapeutic target for inflammation, pain, immune health, energy balance, digestion, memory, and embryogenesis (7).

What Is Endocannabinoid Deficiency

If your endocannabinoid system is not working properly, it cannot get your body back into balance. According to a 2014 review published in Neuro Endocrinology Letters, clinical endocannabinoid deficiency (CECD) may lead to a number of health issues, including migraines, fibromyalgia, and irritable bowel syndrome (8). According to a 2018 review published in Acta Neuropsychiatrica, poor cannabinoid signaling may lead to psychiatric and neurological disorders, including anxiety, depression, schizophrenia, Alzheimer’s disease, and stroke (9). Researchers found that using cannabis may help to improve symptoms related to CECD.

Cannabinoids, Inflammation, and Pain

One of the most common uses of CBD and marijuana is to reduce inflammation and pain. This is not a new idea. Marijuana has been used since 2900 BC for its pain-reducing effects (10).

But how does this work? Your endocannabinoid system helps to regulate a number of functions to create homeostasis. As endocannabinoids made by your body bind to your cannabinoid receptors, they can regulate inflammation, pain, and other things in your body (11, 12).

However, if there is an endocannabinoid deficiency, cannabinoids like CBD can step in. A 2007 study published in the European Journal of Pharmacology has found that CBD may help to reduce chronic inflammation, chronic inflammatory pain, and neuropathic pain (13). Other studies have shown that CBD and marijuana may help to reduce inflammation and pain in rheumatoid arthritis, multiple sclerosis, and other health issues (14, 15, 16, 17, 18, 19, 20).

It may not be surprising but cannabinoids may also be helpful for inflammation, pain, and other symptoms related to mast cell activation. Let’s explore the connection between mast cells and cannabinoids in the upcoming sections. But before I jump into the link between mast cells and cannabinoids, I want to go over what mast cells and mast cell activation are.

What Are Mast Cells

Your mast cells are a type of white blood cells in connective tissues, including your digestive tract, skin, respiratory tract, urinary tract, reproductive organs, surrounding your nerves, and near your blood vessels and lymph vessels. They are in charge of storing histamine and other inflammatory mast cell mediators. If you are exposed to an allergen, chemical, foreign pathogen, or other triggers, your mas cells will release these inflammatory mediators to fight invaders and protect your body. Though your mast cells are essential for a healthy body, overactive mast cells can increase your risk of mast cell disorders, including mast cell activation syndrome (MCAS). MCAS is a complex health condition that can cause chronic inflammation and widespread symptoms.

Symptoms of Mast Cell Activation Syndrome

You may notice that many symptoms of MCAS are similar to histamine intolerance. Just like with histamine intolerance, symptoms of MCAS may vary from person to person.

Your symptoms of MCAS may include:

  • Rashes, eczema, and other skin issues

  • Hives

  • Itching

  • Low blood pressure

  • Heart palpitations

  • Chest pain

  • Headaches of migraines

  • Fatigue

  • Brain fog

  • Weakness

  • Dizziness

  • Loss of appetite or low appetite

  • Rapid weight loss or weight gain

  • Rhinitis

  • Gastrointestinal troubles, including abdominal pain, diarrhea, nausea, and vomiting

  • Nervous system symptoms, such as anxiety

  • Vision changes

Cannabinoids and Mast Cells

Research on the potential therapeutic effects of cannabinoids on mast cell activation is not new. It dates back several decades. A 1995 study published in the Proceedings of the National Academy of Sciences of the United States of America has found that CB2 cannabinoid receptors may be found on mast cells and may play a role in mast cell activation and inflammation (21). A 1998 study published in Immunopharmacology has found that cannabinoids may help to reduce inflammatory cytokines released by your mast cells (22).

A 2005 study published in the Journal of Dermatological Science has found that distributing CB1 and CB2 cannabinoid receptors on mast cells and skin nerve fibers have helped to reduce inflammation (23). A 2008 review published in the Journal of Neuroendocrinology has found that cannabinomimetic compounds may help to regulate mast cell activation and reduce the inflammatory response in inflammatory gastrointestinal syndrome, dermatitis, and other inflammatory health issues (24).

A 2016 study published in Haematologica has found that cannabinoids may mitigate inflammation, mast cell activation, and neurologic inflammation in sickle cell anemia (25). A 2017 review published in Pain Physician has found that cannabinoids may have analgesic properties and may help to reduce pain and symptoms in mast cell activation disease (MCAD) (26). Furthermore, a 2020 review published in the International Archives of Allergy and Immunology has found that cannabinoids may help to reduce inflammation and symptoms in allergic diseases, including atopic dermatitis and asthma (27).

Though we still need more research to completely understand the potential benefits of cannabinoids on mast cell activation problems, existing research and anecdotal evidence suggests that cannabinoids offer anti-inflammatory, pain-reducing, and other therapeutic benefits. Many people find using CBD oil in the evening especially useful as it helps relaxation, reduces pain, and supports sleep.

How to Use Cannabinoids for Mast Cell Activation

There are a number of ways you can use cannabinoids for inflammation and mast cell activation. You may use CBD oil orally in CBD oil capsules, pills, or droppers. You may use sublingual CBD oil by applying it under your tongue. You may use it topically for CBD lotions, body butter, creams, rollers, soaps, and shampoo. You may also inhale CBD oil through a vaporizer. You may also find chocolate and other snacks made with CBD. You may use marijuana with THC in very similar ways, including pills, tablets, capsules, tinctures, powders, transdermal patches, topicals, edibles, vaping, and of course, smoking.

Next Steps

Are you interested to see how cannabinoids may help to support your health? Working with a healthcare practitioner knowledgeable about histamine intolerance and MCAS is the best way to get to the root cause of your symptoms and create an individualized treatment. I welcome you to start a personalized functional medicine consultation with me for further guidance to improve your health. You may book your consultation here. Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.


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