BACKGROUND In recent years, codeine-containing cough syrups (CCS) have been reported as substances of abuse, especially in adolescents. Chronic CCS abuse can induce physical and psychological dependence. However, the potential brain impairment caused by chronic CCS abuse has not been reported previously. The present study was designed to determine if the striatal dopamine transporter (DAT) levels measured by (99m)Tc-TRODAT-1 single photon emission computed tomography (SPECT) brain scans were altered in CCS-dependent subjects and to explore the CCS-caused brain impairment. METHODS SPECT brain scans were acquired on 22 CCS-dependent subjects and 27 healthy age matched controls. The volume (V) and weight (W) of bilateral corpus striatum as well as the (99m)Tc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra) were calculated using mathematical models. RESULTS It was displayed that DAT availability of striatum was significantly decreased and the V, W and Ra were greatly reduced in the CCS-dependent group compared to controls (for each comparison p<0.01). CONCLUSIONS Taken together, these results suggest that chronic CCS abuse may cause serious damage to the brain and the neuroimaging findings further illustrate the mechanism of CCS dependence.