BACKGROUND: A growing body of evidence suggests that crack cocaine misuse has widespread systemic and cognitive consequences, but little attention has been given to its systemic pathophysiology. We report here changes in inflammation markers, oxidative damage and brain derived neurotrophic factor in a sample of outpatients with crack cocaine use disorders. METHODS: Fifty-three outpatients were recruited for this cross-sectional study and matched with fifty control subjects. The focus of this report is in between group differences in cytokines, oxidative damage and brain-derived neurotrophic factor (BDNF). RESULTS: Crack cocaine use was associated with higher BDNF levels when compared to controls, present only in those who used crack cocaine in the last month. Patients also had higher circulating levels of IL-1β, TNF-α and IL-10 when compared to controls. There were no significant differences in oxidative damage between patients and controls. CONCLUSIONS: These results represent a first demonstration that crack cocaine use disorders entail an activation of the reward, immune and inflammatory systems.