Cannabis reduces inflammation by suppressing the immune system. It can also boost the immune system in the fight against cancer cells. How can it be both at the same time?
It is becoming increasingly clear that both endocannabinoids (in the body) and cannabinoids (in the plant) have the potential to interact with immune system functioning. The evolution of the immune system is arguably one of the cleverest aspects of human physiology, but it can bring our demise with autoimmune disease or catastrophic reactions, such as anaphylactic shock. Cannabis modulates the immune system, but is that in the right direction?
Rheumatoid arthritis, multiple sclerosis, Lupus, PANDAS, and Hashimoto’s thyroiditis are just a few examples of disease state resulting from an immune system gone awry. Cannabis successfully treats some of the symptoms of these conditions, namely inflammation, so it becomes very important that the therapeutic use of cannabinoids modulate immune functioning in the right direction. You don’t want cannabis to suppress the immune system if you’re using immunotherapy to fight cancer, and you don’t want it to activate and make an autoimmune condition worse.
Cannabis and the Body’s Receptors
CB1 receptor is widely expressed in the nervous system, while CB2 is mainly expressed by the cells of the immune system. Therefore, any modulatory effects of cannabis will be mediated through the CB2 receptor.
This seems fairly straight forward until you find out that cannabinoids can also activate other receptors that are important to immune system functioning: TRPV1, PPARa and PPARg and GPR55. And that’s where things get weird for cannabis medicine.
Innate and Adaptive Immunity
The immune system has two divisions: innate and adaptive.
Innate, or nonspecific, immunity is what your mama gave you; you were born with it. This includes monocytes and macrophages (that attack and absorb foreign bodies), as well as cytokines and chemokines (secreted by immune cells to neutralize agents of infection via multiple mechanisms, typically resulting in inflammation). We can appreciate that this branch of the immune system is crucial in maintaining homeostasis of the body, as well as bringing the body back to homeostasis after infection.
The role of cannabinoids in reducing inflammation has been described extensively. CBD has shown to reduce pro-inflammatory signals (i.e. cytokines) via CB2 receptor signaling mechanisms. Therefore, cannabinoids can be viewed as boosting the immune response, since essentially innate immunity function is improved with cannabis-mediated signaling: cleaning up the inflammation in the local tissue sites where there is an infection.
Adaptive immunity, on the other hand, is regulated by killer T-cells, B-cells, and antibodies of the immune system. These are built by exposure to infection or vaccine. As such, this branch is extremely important in recognizing and attacking cells that are out of control (i.e. cancer cells), or in mounting an allergic response via recruitment of specific type of antibody called IgE.
Cannabinoids, The Immune System, and Cancer
As far as adaptive immune function is concerned, the role of cannabinoids in its modulation is less clear. Perhaps one of the most demonstrative pieces of evidence for this is in cancer. For example, one study reported differential effects on cancer progression depending on the dose of cannabinoids: low-dose were pro-proliferative in cancer cells, while higher doses were anti-proliferative and pro-apoptotic.
It is important to note that adaptive immunity is involved in recognizing, attacking and cleaning up cancer cells. This study highlights a potential bimodal action of cannabinoids on cancer cell growth, where the effect is dose dependent. Therefore, it is tempting to speculate that cancer growth is arrested, and adaptive immunity boosted at higher doses of cannabinoids (micromolar range).
However, another concern about using cannabinoids in cancer treatment is due to their reported immunosuppressive actions via CB2 receptor stimulation in immune cells. THC has been reported to exert immunosuppressive effects in vitro and in vivo on macrophages and T cells of the immune system.
This might be explained by changes in the cannabinoid receptor levels in cancer. CB1 receptor has been shown to be reduced in malignant cells. In liver cancer, higher abundance of CB1 and CB2 receptor correlated with improved prognosis.
Does cannabis boost immune system function? Yes and no, the answer is not so clear cut. The relevant issues seem to involve dosage, the disease it is being used for, and the receptor numbers in the target tissue. Additionally, we don’t always want our immune system to be revved-up because that can lead exacerbating autoimmune diseases.
Cannabinoid signaling keeps innate immunity in check, which is as important as having the ability to boost immune function. After all, inflammatory environment is associated with development of a myriad of other disease, including cancer. We just may have struck gold with the discoveries surrounding the anti-inflammatory properties of cannabinoids.