Cannabis Oil and Exploratory Gut-Immune Signatures During Breast Cancer Chemotherapy: A Randomized Pilot Trial

Background: Approximately 42% of breast cancer patients report cannabis use for chemotherapy-related symptom relief, yet its impact on the gut-immune axis remains unexplored. This trial evaluated the feasibility of monitoring short-chain fatty acids (SCFAs) and systemic cytokines as exploratory biomarkers during cannabis oil intervention. Method: In a double-blind, placebo-controlled pilot trial, women with breast cancer (n = 10) receiving chemotherapy were randomized to cannabis oil (n = 6) or placebo (n = 4) for 12 weeks. Fecal SCFAs and plasma cytokines were analyzed in paired samples. Results: Dietary stability was systematically assessed using a food frequency questionnaire, with stability defined as <30% shift in functional protein and fiber indices. High dietary stability was confirmed, with all participants maintaining consistent intake of fermentation substrates. Numerical trends, none reaching statistical significance (all p > 0.05), were observed in both exploratory endpoints. Fecal short-chain fatty acid profiling revealed a descriptive numerical reduction in the proteolytic dysbiosis marker iso-butyric acid within the cannabis arm compared with a marginal increase in placebo. Directionally, the cannabis group demonstrated greater median reductions in inflammatory cytokines such as IL-6, IL-8, IL-1β, and TNF-⍺ whereas the placebo group exhibited persistent or heterogeneous profiles. Conclusions: These directional trends toward reduced proteolytic metabolites and attenuated systemic cytokines suggest possible associations between cannabis oil exposure and exploratory gut microbial and immune biomarkers. Given the small pilot sample size, these hypothesis-generating findings lack formal statistical power but warrant adequately powered confirmatory trials.