Background: Pre-clinical studies link cannabinoid-1 receptor activation to inflammation and atherosclerotic effects; anti-inflammation and immunosuppression seem to be mediated by cannabinoid-2 receptor activation. In this epidemiological study, we aim to present estimates on suspected cannabis-attributable immunomodulation as manifest in serum C-reactive protein (CRP) levels as non-specific inflammatory markers with interpretable clinical values. With strength of data from recent large nationally representative community sample surveys, the research approach illustrates value of a quantile regressions approach in lieu of the commonly used but relatively arbitrary cutpoints for CRP values. Methods: The study population encompasses 20-59 year old participants from the National Health and Nutrition Examination Surveys, 2005-2010 (n = 1115 recently active cannabis smokers and 8041 nonsmokers, identified via confidential Audio Computer Assisted Self-Interviews). Age, sex, race, education, income-poverty ratio, alcohol consumption, and tobacco smoking also were measured, together with body mass index (BMI), which actually might be on a mediational path. Quantile regressions, with boot-strapping for variance estimation, made it possible to hold these covariates constant while estimating cannabis-CRP associations. Results: Evidence suggesting possible cannabis-attributable immunomodulation emerges at CRP levels below the median (p < 0.05). Whereas BMI might help explain a cannabis link with serum CRP, but BMI-stratified analyses disclosed no appreciable variation of the cannabis-CRP relationship across BMI subgroups. Conclusions: Extending pre-clinical research on cannabis-attributable immunomodulation, this study's CRP evidence points toward possible anti-inflammatory effects of cannabis smoking. More definitive evidence can be derived by combining pre-clinical research, studies of patients, and epidemiological research approaches. (C) 2014 Elsevier Ireland Ltd. All rights reserved.