Cannabis smoking increases systemic inflammation and reduces immunity

Introduction: Cannabis is the most used federally illegal drug in the United States with a percentage increased from 19.0% in 2021 to 22.3% in 2024 among people aged 12 or older. Smoking remains the most common mode of cannabis use, even among cancer patients. Despite the anti-inflammatory potential of certain cannabinoids, cannabis smoke contains numerous carcinogens and toxicants that can potentially disrupt immune homeostasis and heighten inflammation. Understanding these effects is crucial as inflammation and immune function shape cancer development, progression, and therapeutic response. Objective: To characterize systemic inflammation and immune alterations associated with cannabis smoking. Methods: Following IRB approval, 44 participants were recruited via Redcap, a secure online survey. Demographics, substance use data, and blood samples were collected for a total of 24 non-users (NU) and 20 exclusive cannabis users (CAN) who smoke cannabis at least bi-weekly over the past month. Users of tobacco products, including blunts and e-cigarettes, were excluded. Product use status was biochemically verified using liquid chromatography tandem mass spectrometry (LC-MS) to quantify THC and its metabolite THC-COOH. Complete blood count (CBC) was obtained on each participant and (CBC)-derived inflammatory markers were calculated. A novel 13-antibody multiparametric flow cytometry panel was used to separate 21 immune cell subsets characterizing both myeloid and lymphoid cells. Data was analyzed using Welch's t-tests. Results: Our CBC data show significantly higher red blood cell distribution width-standard deviation (p=0.038) and lower absolute number of monocytes (p=0.038) in CAN users compared to NU. We also observed a significant increase in platelet-to-lymphocyte ratio in CAN users vs NU (p=0.028). Our myeloid immune cell phenotyping data show that cannabis smokers have significantly higher number of low-density neutrophils (LDNs) than NU (p=0.035). Preliminary lymphoid immune cell phenotyping data suggest that cannabis smokers have significantly fewer B cells (p= 0.014) and activated B cells (p= 0.016) than NU. Our preliminary data also show a non-significant decrease in CD8⁺ T cells. These findings indicate that cannabis smoking induces systemic inflammation (higher PLR and LDNs) and suppresses immune responses (fewer B and CD8+ T cells). Conclusions: Our data demonstrate for the first time that cannabis smoking induces a proinflammatory and immunosuppressive state that may promote diverse human diseases, including cancer. We established the first comprehensive framework to evaluate the immunological effects of cannabis smoking. These findings reveal how cannabis use profoundly alters the immune system at both cellular and functional levels. Grant support: NIH/NCI (R01CA242168, Queimado); TSET HPRC (Queimado); PHF Bridge (Queimado); NIH/ NIGMS (U54GM104938-10)