The use of cannabis and its products among cancer patients to relieve anti-cancer side effects treatments is widespread. While many in-vitro studies demonstrated that the cannabis plant has a broad, largely immunosuppressive effect on the immune system, the clinical consequences of cannabis consumption and its effects on the immune system are unclear, particularly in oncology. In our recent prospective clinical study and one of the first of its kind, we provided the first indication of the effect of cannabis use among cancer patients who began immunotherapy and showed a correlation between cannabis consumption before and during immunotherapy and poor clinical outcomes. Our comparative follow-up study found that while cannabis consumption significantly reduced treatment side effects, it shortened the time to tumor progression and caused a significant decrease in overall survival. Thus, our study is the first to demonstrate the potential adverse effects of cannabis use by advanced cancer patients starting immunotherapy and suggests considering its use very carefully during anti-cancer therapies.