CANNABINOIDS AND THE IMMUNE SYSTEM: A DIFFICULT BALANCING ACT

Much of the new research with cannabis points toward cannabinoids having an adaptive, immunomodulating effect, rather than just suppressing of the immune activity.

Cannabis sativa has been used for health and nutritional purposes for thousands of years throughout the world. Many ancient civilizations –especially the Chinese and Greeks – included cannabis in their pharmacopoeia as having medicinal properties for many ailments. At this time, no one questioned how or why cannabis relieved pain and calmed the spirits. It effects were beneficial and that’s what mattered.

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Now we move forward into the 21st century. Medical Researcher are trying to understand not only the molecular makeup of cannabis, but also how it interacts with the biological systems, which are complex, in our bodies. Despite many exciting results, we still know relatively little of the total potential of the cannabis plants, especially when it comes to the interactions between cannabis and our immune systems.

Studies have suggested that cannabinoids like THC and CBD are immunosuppressants, which could explain the relief experienced by medical cannabis users with autoimmune diseases and chronic inflammation. While other studies have shown that regular cannabis use can increase white blood cell counts in immunodeficiency disorders such as HIV, suggesting an immune-boosting effect.

It gets much more complicated when we consider that the effects of cannabis are mediated predominately  by the endocannabinoid system, which scientists believe interacts with all biological activities, including the human immune system.

The truth is that much remains to be discovered about how cannabis affects our immune system. Here’s some of what we know so far.

OVERVIEW -IMMUNE SYSTEM

Our bodies constantly exposed to infectious diseases, bacteria and viruses, all intent on running our bodies down and feeding upon them which weaken our bodies at least for a time. Without any immune defenses to keep these invaders controlled, we’d all for a short time on this planet. Thankfully we have an immune system:  which is made up of a complex network of cells, tissues and organs, running with remarkable precision to keep us healthy.

A main player in our immune system’s arsenal are white blood cells or leukocytes, they seek out and destroy any unwanted visitors like bacteria, viruses and even trauma. Leukocytes can be divided into two groups:

1) Lymphocytes (B cells and T cells) that destroy antigens and help the body to remember past infections or attackers.

2) Phagocytes which absorb and neutralize foreign pathogens and substances that might enter our bodies.

Most of us are familiar with T cells because of their relationship with the HIV virus, which wipes out those T-cells; this is why HIV patients are vulnerable to normally harmless infections.

The human immune system as well plays a key role in detecting faulty cells inside our bodies, and, through the process of cell death, ensures that these cells do not continue to grow and become tumors.

Killing off of certain bad cells is a crucial element of a healthy functioning immune system, which maintains a delicate balance between growth and death. As an example, there is too many cells dying, autoimmune diseases can result, while too many cells  can create the perfect environment for cancer.

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THE ENDOCANNABINOID SYSTEM AND THE IMMUNE SYSTEM

Optimal immune function entails a intricate balancing act that relies on constant communication between our immune cells, tissues, and organs. Since the discovery of the human endocannabinoid system (ECS) in the 1990s, we have found another key piece of the puzzle.

The endocannabinoid system comprises two main G protein-coupled receptors (CB1 and CB2), the known human endocannabinoids (anandamide and 2-AG), along with  the proteins that transport our endocannabinoids and the enzymes that break them down in the body.

The ECS is a Good regulator – continually working to maintain a state of biological balance.

Endocannabinoids are produced when needed, travelling backwards across chemical synapses and determining cell activity. This at least in part explains why the ECS has been termed a homeostatic regulator – continually working to maintain a state of balance within our biologic systems.

The ECS regulates numerous physiological processes, including immune function and inflammation. Both CB1 and CB2 receptors can be found on immune cells, although there are between 10-100 times more CB2 receptors than CB1. Endocannabinoids act upon immune cells directly through the CB2 receptor.

CB2 receptor activation helps create an anti-inflammatory effect and is therefore a therapeutic target for autoimmune disorders and neurodegenerative disease. though, any ECS immunosuppressant activity is thought to be transitory, and can be overridden when necessary in the presence of any  type of infection.

Scientists have found that plant cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD) impact our health by interacting in different ways with our endocannabinoid systems. Therefore, it makes sense that consuming medical cannabis will also directly affect our immune system. But researchers have struggled to understand exactly how.

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THE IMMUNE SYSTEM AND  CANNABIS

When talking about cannabis, we’re dealing with numerous and as many as 400 different molecules. These include the more frequently studied cannabinoids like THC and CBD, more than 100 other minor cannabinoids, dozens of terpenes, and a host of flavonoids – the combination of which varies according to the cannabis strain and species. These molecules can be quite different in percentages based on hybridization of the cannabis plants selecting for different amounts of certain compounds.

Though most work has been carried out on individual cannabinoids, in particular THC and CBD, if you’re looking for some solid conclusions about how they affect the immune system, think again.

THC has been the focus of the majority of the research. THC binds to the CB2 receptor and activates it, which has an anti-inflammatory effect. This suggests that THC is immunosuppressant. Accordingly, THC is thought to show great help for autoimmune diseases, as Crohn’s and MS.  CBD (cannabidiol), despite little binding affinity with cannabinoid receptors, is also considered to be immunosuppressant, reducing cytokine production and inhibiting T-cell function.

But that’s only part of the story. New  research and mounting subjective evidence points towards cannabinoids having an adaptive, immunomodulating effect, rather than just suppressing immune activity.

HIV AND CANNABIS

Medical cannabis is a commonly used in palliative treatment for HIV thanks to the plant’s ability to reduce anxiety, improve appetite, and ease pain. But recent research takes THC’s role even further, suggesting that it can actually up regulate the immune system, potentially improving patient therapeutic effects.

Preclinical research had corroborated the view that THC was immunosuppressant in HIV, increasing viral load and worsening the disease. Recent research, however, has suggested it’s immune-stimulating effects.

In 2011 study by Louisiana State University,  scientists revealed astonishing results when monkeys were given THC over 28 days prior to SIV infection (a similar version of the virus). THC appeared to have protective effect of some modality, lengthening the lives of the monkeys and reducing viral infections.

Scientists discovered that infection-fighting cell counts were higher in HIV patients using cannabis.

Continued research by the same team in 2014 took these findings a step further. This time monkeys were given THC for a longer period of seventeen months before introducing SIV infection. Notably  there was an increase in T-cells and a reduction in viral load, also THC appeared to have protected the monkeys against the intestinal damage commonly caused by the virus.

These results have also been replicated in humans. In a study conducted by researchers at universities in Virginia and Florida, CD4 and CD8 white blood cell counts were compared in a sample of 95 HIV patients, some of whom were chronic cannabis users.  Scientists found that both types of infection-fighting immune counts were higher in patients using cannabis, signifying their immune systems had been bolstered by the plant.

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CANCER, CANNABIS, AND OUR IMMUNE SYSTEM

Sadly Cancer will affect one in two of us at some point in our lifetime. There’s no hard and fast rule why it appears, but most cancers share the same or similar mechanisms.

Our immune system is prepared to spot rogue cells and, through mechanisms such as apoptosis, eliminate any that might become tumors. Unfortunately, cancer cells can outmaneuver our immune system by getting it to work in their favor.

Esther Martinez, a cannabinoid research scientist at Madrid’s Complutense University, describes a kind of cross communication between cancer cells and the immune system. “When the tumor talks with immune cells, it reverses the signal,”. “So, it’s like, ‘I’m here, and now I want you to work for me.’ And instead of attacking the tumor, it gives pro-survival signals, so the immune system around the cancer goes through a transformation. In short the tumors have the capacity to shut off the immune system.”

With the immune system defenseless, cancer cells then grow uncontrolled. Only recently, the only approved anticancer weapons have been harsh treatments like chemotherapy, which destroy not only the cancer cells, but also fast-growing, healthy cells.

It’s without surprise, that tremendous excitement lies around the antitumor properties of the cannabis plant, in particular THC and CBD. In fact, it was Esther’s colleagues at the Complutense University, Manuel Guzman and Cristina Sanchez, who paved the way in investigating the cancer-killing effects of cannabinoids, primarily, but not exclusively through apoptosis.

However, little is known about the relationship between the immune system and cannabinoids in this process. One reason is that in many preclinical trials, human tumors grafted onto immunosuppressed mice are used to avoid rejection by their rodent hosts.

Some studies do are using immune competent mice, such as Dr Wai Liu’s 2014 report, which examined the effects of THC and CBD on brain tumors when combined with radiotherapy. Not only were the tumors significantly reduced, but little to no immune suppression was witnessed in the study, according to Dr Liu, a London-based Research Fellow and cannabinoid Scientist.

This is welcomed news, as cannabinoids can also cause apoptosis in lymphocyte cells, potentially suppressing the immune system. The ability of cannabinoids to both suppress and bolster immune function lends credibility to the idea that the endocannabinoid system is involved in immune-modulation, as Dr. Liu said: “I suspect that cannabinoids are having a double-punch effect of 1) direct killing and 2) enhancing immunity by suppressing those immune cells that serve to hold back the immune-based killing cells.”

 

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CANCER  IMMUNE THERAPY

Indecision about the interaction between cannabinoids and the immune system raises doubts regarding the use of medical cannabis during immunotherapy. Proclaimed the wonder cancer treatment of the future, immunotherapy directs and helps white blood cells to detect and kill cancer in the body. So far, however, there has only been one study examining how cannabinoids may affect this process – and the results were challenging.

Conducted at the Rambam Medical Centre in Haifa, Israel, patients taking medical cannabis alongside the immunotherapy cancer drug  Nivolumab responded 50% less compared to those on immunotherapy alone. Curiously, subjects taking medical cannabis high in THC responded better to immunotherapy than those on a low strength THC product. No considerable change in overall survival rates for patients was noted.

There are also subjective reports from California cancer patients who maintain that they benefited by combining immunotherapy with a low-dose, CBD-rich cannabis oil regimen under a doctor’s supervision. In addition, a small but mounting body of preclinical data suggests that combining CBD and THC with conventional chemotherapy and radiation could have a powerful synergistic effect as an a cancer treatment. But these findings have not been replicated in human trials.

Cannabis is immunosuppressive when there is an over aggressive immune response, but otherwise it regulates and corrects the immune system, bringing balance to the organism.

Despite a lack of simplicity regarding cannabinoids and immunotherapy, the predominance of scientific data suggests that it’s time to abandon the antiquated and misleading immunosuppressant label and embrace the idea that cannabinoids can also work as immunomodulators. This is what Dr. Mariano Garcia de Palau, a Spanish cannabis clinician and member of the Spanish Medical Cannabis Observatory, has seen in patients within his practice.

“I believe [cannabis] is immunosuppressive when there is hyper-immune response,” says Dr. Garcia de Palau, “but otherwise it regulates and corrects the immune system. In fact, you could say it functions like the endocannabinoid system, bringing equilibrium to the organism.”

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What does this mean in realistic terms; if you commonly use cannabis, have a compromised immune system and or are starting immunotherapy? Consult with your medical practitioner. In the meantime, we can only hope research will help us better understand the multifaceted relationship between the endocannabinoid system, our immune response, and compounds in cannabis.