Serum Zonulin Levels in Patients with Heroin Addiction

Opioid use has been associated with alterations in gut-brain axis signaling and intestinal barrier function. Zonulin, a key regulator of intestinal permeability, has been implicated in various neuropsychiatric and inflammatory conditions; however, its role in heroin addiction and remission remains poorly understood. This study aimed to investigate serum zonulin levels in patients with heroin addiction (HA) during active heroin use (AHU) and remission (R) and to compare these levels with those of healthy controls (C).

A total of 104 male participants were included: patients with AHU, patients in remission under buprenorphine/naloxone maintenance treatment, and C. Serum zonulin levels were measured using an enzyme-linked immunosorbent assay. Group comparisons and correlation analyses were performed, and receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory value of zonulin.

The scores of addiction diagnostic criteria, the severity of craving, and the total API score were significantly higher in the AHU group than in the R group. The difference between the groups was significant when the R, AHU, and C groups were compared for zonulin levels (p=0.02). This difference was due to zonulin levels being higher in the R group than in the C group. When the HA (R+AHU) and C groups were compared for zonulin levels, zonulin levels were significantly higher in the HA group than in the C group (p=0.00). In the ROC analysis, the highest area under the curve (AUC) values were obtained in the R-C group comparison and the HA-C group comparison (AUC=0.683 and AUC=0.650, respectively).

These findings suggest that increased intestinal permeability, as reflected by elevated serum zonulin levels, may persist during the remission phase of heroin addiction. However, given the cross-sectional design and the fact that remission was defined as a medication-stabilized state under buprenorphine treatment, these results should be interpreted cautiously. Longitudinal studies incorporating follow-up assessments and gut microbiota analyses are warranted to clarify the temporal dynamics and clinical significance of zonulin alterations in heroin addiction.