The Immunomodulatory Effects of CBD

We recently published an article about the immunomodulatory effects of cannabis as a whole and now we want to go into a little bit more detail about CBD in particular. Immunomodulation is arguably the most important medical aspect of cannabis and the immunomodulatory effects of CBD can’t be understated.

From topical inflammation reduction to systemic reduction in inflammatory cytokines, CBD shows great potential in a number of diseases — even including Type 1 diabetes. Notice how CBD shows an overall immuno-suppressive quality. That means that its clinical application is typically to reduce pathological immune responses but not usually the other way around.

Interestingly, it appears to scientists that the immunomodulatory effects of CBD are mediated, not through cannabinoid receptors, but through other mechanisms in the body. This makes CBD extremely interesting and complex, but we’ll do our best to break down some of the science behind how CBD works in the immune system and what clinical significance that has for modern medicine.

Mechanisms of CBD in the immune system.

There are a number of different mechanisms by which CBD has been identified to exert its effects through the immune system. Consider the immune system; it’s made up of various types of cells with a common cause: kill pathogens. Because the process of killing pathogens is complicated, different cells do different things. For example, immune cells known as T cells can produce signalling molecules that activate other immune cells. There are also B cells that can produce antibodies and have memory.

And so there are a number of different ways to measure how CBD might work through the immune system. To understand how CBD works in the immune system, scientists can measure the levels of certain inflammatory cytokines (chemicals produced by T cells), the rate of apoptosis (cell death), and by measuring intermediary compounds in the inflammatory process.

CBD has showed results in a number of these different measurable outcomes and when we have a look through them, it might become clearer the different stages in the inflammatory process that CBD can interfere with.

Immunosuppresion via the neuro-immune axis.

In one study, scientists uncovered a neuro-immune axis by which CBD exerts axis on the immune system of the human intestine. The gut is an interesting example because it has its own nervous system called the enteric nervous system. Glial cells are a part of this enteric nervous system and they play an active role in inflammation; they release neurotrophins and other chemical signals that trigger other cells to begin the inflammatory process. 

In the research, scientists demonstrated CBD’s capacity to reduce the reactive response of glial cells, thereby reducing the amount of inflammatory cytokines. But it doesn’t do this via any kind of endocannabinoid receptor on glial cells; rather, scientists concluded that CBD exerts anti-inflammtory and immunosuppressive qualities via the PPAR gamma receptor pathway. 

It’s important to remember that this doesn’t mean this is where CBD’s anti-inflammatory qualities stop in the gastrointestinal system (GIT). For example, the GIT is rich with cannabinoid receptors and so changes to the endocannabinoid system caused by CBD ingestion will likely have an effect in the GIT. However, through this investigation it becomes clear the myriad ways that CBD can exert an anti-inflammatory or immunosuppressive effect.

Immunosuppression via apoptosis.

Apoptosis refers to cell death. Cell death isn’t a bad thing — it’s a very important thing. Imagine your skin cells never died and they continued to grow. Your skin would grow too thick to be healthy. It’s the same with tissues and organs. Cells need to die and then new ones need to take their place. This is especially true if we’re talking about immunity because the best fate for infected cells is death. This way, the pathogen doesn’t continue to replicate and cause ill health to the organism.

In this study, researchers showed that CBD is able to induce apoptosis in human monocytes. Monocytes are a particular kind of white blood cell (white blood cells form part of the immune system). They are large cells that differentiate into macrophages and other kinds of immune cells. They are typically higher in level when the body is fighting a pathogen, and so they are used as a marker for increased or pathological inflammation.

This is why it’s relevant that CBD is able to increase apoptosis rates of human monocytes. For the nerdy soul whose wondering, it does this by increasing mitochondrial permeability and causing oxidative stress to the point of apoptosis. 

There are a number of other studies that show CBD’s ability to induce apoptosis in in vitro murine and human cells.

Immunosuppression via gene alteration.

This is an especially interesting aspect of the way CBD can alter the human immune response. Scientists of this research tested CBD on human gingival mesenchymal stem cells and tested for a number of different biomarkers and surface antigens. Incredibly, researchers found that CBD was able to downregulate genes codifying for antigens that activate the immune system.

This study is the only one of its kind, although this kind of research has taken place with respect to cancer rather than specifically the immune system. It’s also important to remember that this study took place in a petri dish and not a human, and it’s never clear whether it’s translatable until it’s tested in a human.

It does begin to shed light on the depth that CBD is able to reach within the human cell, sometimes even altering the immune response through gene expression.

The clinical significance of CBD.

The anti-inflammatory or immunosuppressive effects of CBD are its most sought after effects. It is these qualities that put it under the spotlight for cancer, multiple sclerosis, Crohn’s disease, Alzheimer’s disease, and fibromyalgia. The reality is that there are a lot of modern diseases with some kind of inflammation or immune dysfunction involved. Autoimmune conditions are another great example.

Consider the study we mentioned earlier in this article about CBD’s potential role in the gastrointestinal system. This is an important outcome for those with Crohn’s disease whose symptoms are almost entirely caused by gastrointestinal inflammation.

Looking at cancer in particular, CBD has been shown to inhibit INF-y (interferon-gamma), a cytokine of the immune system that is implicated in different kinds of cancer. It potentially does this by balancing out the various types of cells that do and don’t produce this cytokine, again demonstrating the complexity by which CBD works on the immune system.

This cytokine also plays a role in certain autoimmune diseases and allergies. For example, lupus is a systemic autoimmune disease that affects the whole body. INF-y is highly implicated in lupus, and interestingly CBD has shown value for those with lupus. However, CBD showed specific action against interleukin-6 in this particular disease.

The reason CBD is clinically significant is because there are not many safe ways to suppress immune function. Immunosuppressive therapy often comes with strong side effects, such as hugely increased susceptibility to infections. On top of this, we have very few treatments for autoimmune diseases such as Crohn’s and lupus and CBD poses a novel therapy that could be useful for these treatment resistant conditions.

One cannabinoid doesn’t fit all inflammation.

We’ve clearly demonstrated how complex CBD is and how wondrous its journey through the human immune system is. From this article, it might look like CBD does just about everything in the immune system. But that’s not the whole picture. If anything, it should be clear that every kind of inflammation is different, involving different cells and mediators, and therefore, there’s no one cannabinoid that will solve all inflammatory problems. 

For some people, immune modulation simply means avoiding a certain trigger. Think of those with a peanut allergy. All they have to do to avoid that inflammatory reaction is avoid peanuts — not take CBD! 

The continuing investigation into CBD’s immunomodulatory effects and how these can be correctly, efficiently, and safely applied in the clinical setting is paramount. The increasing incidence of autoimmune disease and immune system-mediated disease necessitates this greater understanding so that cannabis can find its way into the hands of those who need it.

We look forward to getting nitty gritty into the science of other cannabinoids and their effects on the immune system.

Have you used CBD for inflammation or autoimmune disease? How did you use it and was it effective for you? We’d love to hear from you in the comments!