LAUSR

Simple Summary Cannabis is widely used by patients with cancer to help with cancer symptoms and treatment side effects. Though cannabis has immunomodulatory effects, and its consumption among cancer patients needs to be carefully considered due to its potential effects on the immune system. In this report, we provide the first indication of the impact of cannabis consumption during immune checkpoint inhibitors (ICI) immunotherapy cancer treatment and show it may be associated with worsening clinical outcomes. Cancer patients using cannabis showed a significant decrease in time to tumor progression (TTP) and decreased overall survival (OS) compared to nonusers. In contrast, the use of cannabis reduced immune-related adverse events (iAE). Thus, our report constitutes the first warning sign to the use of cannabis as a palliative treatment in advanced cancer patients starting immunotherapy and suggests that its consumption should be used with attentiveness. Furthermore, we show that the levels of endogenous serum eCB and eCB-like lipids are affected by immunotherapy and may potentially constitute monitoring targets to cancer immunotherapy treatment, which currently has poor clinical markers for predicting patient response rates. Abstract Cannabis or its derivatives are widely used by patients with cancer to help with cancer symptoms and treatment side effects. However, cannabis has potent immunomodulatory properties. To determine if cannabis consumption during immunotherapy affects therapy outcomes, we conducted a prospective observatory study including 102 (68 immunotherapy and 34 immunotherapy plus cannabis) consecutive patients with advanced cancers who initiated immunotherapy. Cannabis consumption correlated with a significant decrease in time to tumor progression and overall survival. On the other hand, the use of cannabis reduced therapy-related immune-related adverse events. We also tested the possibility that cannabis may affect the immune system or the tumor microenvironment through the alteration of the endocannabinoid system. We analyzed a panel of serum endocannabinoids (eCBs) and eCB-like lipids, measuring their levels before and after immunotherapy in both groups. Levels of serum eCBs and eCB-like lipids, before immunotherapy, showed no significant differences between cannabis users to nonusers. Nevertheless, the levels of four eCB and eCB-like compounds were associated with patients’ overall survival time. Collectively, cannabis consumption has considerable immunomodulatory effects, and its use among cancer patients needs to be carefully considered due to its potential effects on the immune system, especially during treatment with immunotherapy.