Crack-cocaine abuse and dependence is a severe public health problem. Sometimes, the crack-cocaine smokers show behavioral changes and symptoms very similar to those observed for severe mental disorders, like schizophrenia. Although crackcocaine use can easily be detected in smokers by urine or blood tests, after some time, cocaine biomarkers become untraceable. In addition, schizophrenia diagnosis is limited to clinical interviews, while precise clinical tests for this mental disorder remain unknown. Employing metabolomics based on NMR spectroscopy, herein, we showed that blood serum metabolites might be used for discrimination between crackcocaine users and schizophrenia patients groups. These two groups showed the greatest differences in around eleven keymetabolites. Moreover, seven possible peripheral metabolites might be enough for differentiation of crack-cocaine users and healthy controls. These results may contribute to a better understanding of crack-cocaine biochemical effects, and enable more precise diagnosis when crack-cocaine biomarkers, methylecgonidine or ecgonidine, are absent from the urine or blood of crack-cocaine users.