Cannabis Use During Immunotherapy

Cannabis is widely used by cancer patients to alleviate cancer-related pain, stimulate appetite and reduce nausea and vomiting associated with chemotherapy.  With the growing number of studies citing cannabis as an effective tool to ease the effects of chemotherapy and other cancer-related side effects, oncologists are increasingly more supportive of the use of cannabis by their patients. The FDA-approved THC drug, dronabinol, has also been approved for the treatment of chemotherapy-induced nausea and vomiting in cancer patients. 

Immunotherapies (a form of therapy used to activate the patients’ immune system against the tumors) using CTLA4, PD-1, and PD-L1 antibodies have recently revolutionized cancer treatment and have been approved for the treatment of over 50 cancer types to date. These therapies also are associated with numerous adverse side effects, some of which may be alleviated with cannabis. 

However, doctors and their patients should be aware that cannabis consumption may negatively impact outcomes in patients receiving immunotherapy. Findings from an observational study from Israel suggested that cannabis could reduce tumor response to therapy in patients undergoing treatment with the immunotherapeutic drug nivolumab (PMID: 30670598).  In another study, these same researchers found that the use of cannabis in patients being treated with checkpoint inhibitor immunotherapy drugs led to a shorter time until their tumors progressed (grew in size and/or spread) and a decreased overall survival compared to those patients not using cannabis (PMID: 32872248). 

Now, a study just published in Signal Transduction and Targeted Therapy provides additional evidence that the use of cannabis during cancer immunotherapy may adversely affect cancer outcomes (PMID: 35383142).  The researchers found that in a mouse model, THC and the endogenous cannabinoid anandamide reduced the therapeutic effect of a drug targeting PD-1, ultimately inhibiting anti-tumor immunity.  Moreover, they found that high levels of anandamide in the blood of cancer patients was associated with poor overall survival. Further, they showed that through the CB2 receptor, CNR2, (mainly responsible for regulating the immune system), cannabinoids impaired the function of anti-tumor T-cells by inhibiting JAK-STAT signaling.  The JAK-STAT pathway regulates T-cell-related immune responses by altering the expression of certain cytokines and growth factors.

Indeed, cannabinoids have been shown to suppress the actions of many cells that make up our immune system including T-cells, natural killer cells, dendritic cells and others through various mechanisms in cell, animal and human studies (PMID 35214123).  Related to its medicinal value, this may be beneficial in dampening chronic or persistent inflammatory conditions, such as autoimmune diseases and colitis.  However, its integration with medical treatment warrants further studies. 

In the meanwhile, the bottom line is that although cannabis may have many beneficial effects on human health, individuals undergoing immunotherapy should be considered a susceptible population that can be harmed by cannabis consumption resulting in adverse disease outcomes.  The medical community should also take note of the immunomodulatory effects of cannabis in this susceptible population to reduce the chances of unwanted adverse effects when combining cannabis alongside immunotherapy regimens.