Gray Matter Abnormalities Associated with Long-term Opium Use: A Voxel-Based Morphometry Study

Background Chronic raw opium use can result in opioid use disorder (OUD). Although voxel-based morphometry (VBM) studies have demonstrated decreased gray matter volume (GMV) in heroin-induced OUD, the structural impacts of long-term raw opium consumption remain poorly understood. This study investigated GMV alterations in men with opium-induced OUD and their association with use duration. Methods High-resolution T1-weighted MRI scans were acquired from 28 men with opium-induced OUD (mean use duration 17.89 ± 5.85 years) receiving opium tincture maintenance and 25 age- and education-matched healthy male controls. Whole-brain VBM (CAT12/SPM12) was controlled for age, total intracranial volume, and nicotine use. Analysis used a voxel-level uncorrected threshold of p < 0.05 with cluster-level FDR correction (p < 0.05), along with stricter thresholds (uncorrected p < 0.001, TFCE with FWE), and small-volume correction (SVC). Partial correlation and multiple linear regression investigated clinical associations. Results Whole-brain analysis identified a left-hemisphere cluster of reduced GMV (cluster-level FDR-corrected p = 0.009). No clusters survived p < 0.001 or TFCE with FWE correction. Reductions in the left insula, inferior frontal gyrus, and parahippocampal gyrus remained significant after SVC. Left insula GMV was negatively associated with duration of opium use (partial r = −0.45, p = 0.027; β = −0.48, p = 0.027 in regression). Conclusion Prolonged raw opium use is associated with decreased GMV in areas involved in craving and impulse control. Given that the whole-brain findings were not confirmed by more stringent statistical approaches, the results should be considered exploratory and necessitate replication in larger samples.