Phytocannabinoids and Keeping Your Immune System Healthy

Scientists have called the endocannabinoid system one of the “gatekeepers” of the immune system.¹ The endocannabinoid system is activated in response to immune challenges like viral or bacterial infections, increasing or decreasing many aspects of immunity.² Certain endocannabinoids act on most immune cells and endocannabinoid receptors are also present on these cells.²  This gives you an idea how important the endocannabinoid system is for proper immune function.

As I mentioned in chapter one of this book, endocannabinoids can bind to and activate other receptors besides cannabinoid receptors. These other receptors include the transient receptor potential vanilloid 1 (TRPV1) channel, peroxisome proliferator-activated receptor (PPAR) α and γ, and the orphan G protein-coupled receptor GPR55. All of these receptors are widely expressed in immune cells.3 In addition, the ability of endocannabinoids to regulate immunity in several types of immune cells is due to their actions on PPARα and PPARγ.3 The GPR55 receptor also is specifically expressed on immune cells known as monocytes and natural killer (NK) cells.3

Because the endocannabinoid system can both enhance and suppress immunity, some researchers have questioned whether using phytocannabinoids like CBD can make a person vulnerable to infectious diseases.1 However, as I’ll discuss in this chapter, even those researchers admit it’s really not that simple.1 CBD may both support and suppress the immune system, depending upon the situation.

CBD in Autoimmune Health

The body maintains immunity when various immune cells work together to protect against foreign invaders. At the same time, the immune system must avoid reactions against self-proteins. In autoimmune conditions, the immune system mistakenly targets a person’s own tissues or organs. The body’s own immune system attacks “self” because it believes it is going after a harmful pathogen. In this case, it can be advantageous to calm down the immune system.

In an animal study of autoimmune health, CBD oil given to rodents intravenously weakened the activity of immune cells including T cells, B cells, and both T helper and T cytotoxic lymphocyte subsets.4 These immune cells are involved in the process leading to autoimmune conditions. However, CBD didn’t reduce the activity of natural killer cells, a type of white blood cell, nor the activity of natural killer T NKT cells, which share properties of both NK cells and T cells. These type of cells are responsible for the primary, nonspecific response the immune system wages against viruses or tumors. In fact, CBD at a dose of 2.5 mg/kg increased the total and percentage NKT cell numbers, and the percentage number of NK cells. The researchers concluded, “The results suggest that repeated treatment with cannabidiol inhibits specific immunity by reduction of T, B, T cytotoxic, and T helper cell numbers, and may enhance nonspecific antiviral and antitumor immune response related to NK and NKT cells.”

Indeed, other animal studies have shown CBD can calm the immune response in autoimmune conditions. In research using mice, CBD reduced autoimmune hepatitis.5 It also stopped the development of type-1, autoimmune diabetes in mice.6 Researchers gave CBD to 11 – 14 week old female mice that were either in a latent diabetes stage or had the initial symptoms of the disease. CBD blocked the manifestations of the disease. Only 32% of the mice in the CBD group developed diabetes compared with 86% and 100% of the untreated animals.

In another study, researchers gave CBD to mice with autoimmune myocarditis (inflammation of the heart).7 The animals given CBD experienced significant improvement. Myocarditis is an important cause of heart failure and sudden cardiac death in young adults and adolescents. Often, myocarditis has an autoimmune cause, where the immune system attacks a cardiac protein known as myosin. Conventional immunosuppressive therapies for autoimmune myocarditis often don’t work well and are linked to toxic side effects.

CBD boosts the action of myeloid-derived suppressor cells (MDSCs), one of the main regulatory cells of the immune system.5 These cells spring into action at sites of inflammation. They have the ability to interfere with T cell functions. CBD, by activating TRPV1 vanilloid receptors, can trigger MDSCs.5 This, in turn, can block inflammation and autoimmune hepatitis.5

Another way in which CBD may support autoimmune health is by boosting the activity of regulatory T cells (Treg).8 These types of cells often don’t work as well as they should in people with autoimmune conditions.

CBD Supports a Healthy Inflammatory Response in the Lungs

The lungs can get hit hard during viral infections. There’s some evidence from animal research that CBD may support the health of the lungs. In one study, researchers caused lung injury in mice then gave the animals CBD 6 hours later.9 A day later the study authors measured the results. CBD improved markers of healthy lungs such as decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, and protein concentration. It also reduced levels of inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the lungs.

In another study, this one a mouse model of asthma, CBD reduced inflammation and lung fibrosis.10  In a similar animal study, scientists triggered the development of asthma in rats.11 They later injected CBD into the animals abdominal areas. CBD reduced levels of the inflammatory cytokines IL-4, IL-5, IL-13, IL-6, and TNF-α. It did not reduce levels of the anti-inflammatory cytokine IL-10.

By supporting a healthy inflammatory response in the lungs, CBD may reduce coughing and help people breathe easier, if animal studies are confirmed in humans.

CBD, SARS-CoV-2, and COVID-19

Given CBD’s effects on the lungs and cytokine production, it’s not surprising that some researchers have started to theorize about its potential use in COVID-19. In COVID-19, the body often releases an excessive number of cytokines and other molecules linked to inflammation. This flood of cytokines—known as a cytokine storm—combined with a decrease in natural killer cells is linked to the lung damage, multi-organ failure, and poor outcome that occurs in many patients with COVID-19.

One group of scientists pointed out that there are a number of reasons CBD may support the health of people with COVID-19.12 First, in studies using human tissue, Cannabis sativa (marijuana) that had a high CBD content was able to decrease the expression of two key receptors for SARS-CoV2, the virus that causes COVID-19.12  Second, cannabidiol supports the immune system and works through the PPARγ receptor to produce direct antiviral activity.12 As I mentioned earlier, it may support healthy inflammatory response by reducing the uncontrolled cytokine production that leads to acute lung injury.

Two animal studies strongly suggest CBD may support the health of COVID-19 patients. Acute respiratory distress syndrome (ARDS) is the main cause of death in severe cases of some respiratory viral infections, such as COVID-19. In one study, researchers investigated the effects of CBD on ARDS.13 The scientists caused ARDS and a cytokine storm in mice. Giving the animals CBD led to a drop in cytokine production. What’s more, CBD reduced the symptoms of ARDS.

According to the researchers, “Our results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.”

CBD’s ability to block cytokines and reduce inflammation in the lungs caught the attention of another group of researchers. In a journal article titled, “Acute inflammation and pathogenesis of SARS-CoV-2 infection: Cannabidiol as a potential anti-inflammatory treatment?” these scientists proposed CBD may be useful in COVID-19.14 In this article, the researchers wrote, “Therefore, as SARS-CoV2 induces significant damage through pro-inflammatory cytokine storm mediated by macrophages and other immune cells and based on the fact that CBD has broad anti-inflammatory properties, CBD might represent as a potential anti-inflammatory therapeutic approach against SARS-CoV2-induced inflammation.” These scientists called for more studies in animals and humans to find out for certain if CBD can benefit COVID patients.

Antibacterial Actions of Phytocannabinoids

It’s not just people with viral infections that may benefit from the actions of phytocannabinoids like CBD. Plant-based cannabinoids may go up to bat against bacteria, too. For example, all five of the major cannabinoids in Cannabis sativa—cannabidiol, cannabichromene, cannabigerol, THC, and cannabinol—significantly blocked the activity of methicillin-resistant Staphylococcus aureus (MRSA) strains.15

In addition, some of the terpenes found in CBD-rich hemp oil may have antibacterial actions. For example, α-Pinene significantly weakens MRSA and other bacteria.16 β-amyrin is another example of a terpene in hemp oil that has antimicrobial actions.17 The entourage effect kicks in to support immunity in a synergistic way, with CBD and the terpenes working together.

Soothing Stress to Improve Immunity

Long-lasting stress can weaken your immunity. Feeling overwhelmed in your work and/or home life can make you more vulnerable to colds, flus and other viral infections. Stress can interfere with the endocannabinoid system. Scientists showed this in 12 cosmonauts participating in a greater than 140-day spaceflight mission.18 The usual markers for stress such as cortisol in saliva weren’t changed. However, blood levels of endocannabinoid system components were elevated while the cosmonauts were in-flight, suggesting the endocannabinoid system undergoes changes when the body is under stress. At the same time, the cosmonaut’s immune systems were also affected. White blood cell counts were higher whereas natural killer cell levels fell by almost 60% shortly after landing.

In chapter three of this book, I went into great detail about CBD and stress. However, I want to briefly mention CBD’s stress-soothing actions in this chapter on immunity. Its ability to calm stress may be another way in which it can support immune health.

Gut-Based Immunity

In chapter nine, I’m going to discuss in great detail how CBD can keep your GI tract comfortable and healthy. But it’s worth a mention in this chapter that CBD can support gut-based immunity. A lot of the immune system is located in the GI tract. That’s where large numbers of organized lymphoid tissue and immune cells are located.19 The gut microbiota, the collection of organisms—good and bad—found in the intestines play an important role in a balanced immune response.20 Excessive inflammation in the gut can lead to intestinal permeability (leaky gut), gut microbiota imbalances, and a weak intestinal immune response.21,22 The endocannabinoid system shores up the immune response in the gut. And like cannabinoids produced by the body, CBD supports a healthy intestinal  inflammatory response in human trials.23 By keeping your gut healthy, your overall immune system will stay healthy, too.

The statements mentioned in this content have not been evaluated by the FDA, and are not intended to prevent, diagnosis, or treat any disease. Always work with your personal healthcare provider.

References:

1. Oláh A, Szekanecz Z, Bíró T. Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges. Front Immunol. 2017;8:1487.
2. Chiurchiù V, Battistini L, Maccarrone M. Endocannabinoid signalling in innate and adaptive immunity. Immunology. 2015;144(3):352-364.
3. Chiurchiù V. Endocannabinoids and Immunity. Cannabis Cannabinoid Res. 2016;1(1):59-66.
4. Ignatowska-Jankowska B, Jankowski M, Glac W, Swiergel AH. Cannabidiol-induced lymphopenia does not involve NKT and NK cells. J Physiol Pharmacol. 2009;60 Suppl 3:99-103.
5. Hegde VL, Nagarkatti PS, Nagarkatti M. Role of myeloid-derived suppressor cells in amelioration of experimental autoimmune hepatitis following activation of TRPV1 receptors by cannabidiol. PLoS One. 2011;6(4):e18281.
6. Weiss L, Zeira M, Reich S, et al. Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology. 2008;54(1):244-249.
7. Lee WS, Erdelyi K, Matyas C, et al. Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation. Mol Med. 2016;22:136-146.
8. Nichols JM, Kaplan BLF. Immune Responses Regulated by Cannabidiol. Cannabis Cannabinoid Res. 2020;5(1):12-31.
9. Ribeiro A, Almeida VI, Costola-de-Souza C, et al. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury. Immunopharmacol Immunotoxicol. 2015;37(1):35-41.
10. Vuolo F, Abreu SC, Michels M, et al. Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma. Eur J Pharmacol. 2019;843:251-259.
11. Vuolo F, Petronilho F, Sonai B, et al. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediators Inflamm. 2015;2015:538670.
12. Esposito G, Pesce M, Seguella L, et al. The potential of cannabidiol in the COVID-19 pandemic. Br J Pharmacol. 2020.
13. Khodadadi H SE, Jarrahi A, et al. Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA. Cannabis and Cannabinoid Research. 2020;5(3).
14. Costiniuk CT, Jenabian MA. Acute inflammation and pathogenesis of SARS-CoV-2 infection: Cannabidiol as a potential anti-inflammatory treatment? Cytokine Growth Factor Rev. 2020;53:63-65.
15. Appendino G, Gibbons S, Giana A, et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod. 2008;71(8):1427-1430.
16. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.
17. Viswanathan MB, Jeya Ananthi JD, Sathish Kumar P. Antimicrobial activity of bioactive compounds and leaf extracts in Jatropha tanjorensis. Fitoterapia. 2012;83(7):1153-1159.
18. Buchheim JI, Matzel S, Rykova M, et al. Stress Related Shift Toward Inflammaging in Cosmonauts After Long-Duration Space Flight. Front Physiol. 2019;10:85.
19. Mowat AM, Agace WW. Regional specialization within the intestinal immune system. Nat Rev Immunol. 2014;14(10):667-685.
20. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012;3(1):4-14.
21. Hornby PJ, Prouty SM. Involvement of cannabinoid receptors in gut motility and visceral perception. Br J Pharmacol. 2004;141(8):1335-1345.
22. Cani PD, Plovier H, Van Hul M, et al. Endocannabinoids–at the crossroads between the gut microbiota and host metabolism. Nat Rev Endocrinol. 2016;12(3):133-143.
23. Irving PM, Iqbal T, Nwokolo C, et al. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis. Inflamm Bowel Dis. 2018;24(4):714-724.