The finding of reduced medial orbital frontal cortex (OFC) gray matter (GM) in substance dependent individual (SDI) compared to controls is consistent with previous studies. Franklin et al. were the first to report lower GM in cocaine dependent subjects compared to controls using voxel-based morphometry (VBM) methods (10). They observed lower GM density in ventral medial OFC, anterior cingulate, and anterior insula. Lyoo et al. found lower GM in bilateral medial OFC in opiate dependent subjects compared to controls (11). Less GM was also found in superior and middle frontal and anterior temporal lobes. In both of these studies subjects were using drugs close to or at the time of MR scanning. In Franklin et al., the average number of days cocaine was last used prior to imaging was 15. In the second paper, opiate-dependent persons were on methadone maintenance. Thus, a potentially important difference of the current study is the relatively prolonged abstinence. In this cohort of SDI abstinence averaged 2.4 years for amphetamine and longer for other drugs. Reversible effects of drugs on brain structure have been well
