Early effects of oral naltrexone on craving, resting state and cue-induced brain activation in opioid use disorder: a prospective fMRI study.

BACKGROUND

Opioid use disorder (OUD) is characterized by intense cue-induced craving and high relapse risk. This longitudinal fMRI study investigated whether oral naltrexone (50mg/day) (oral-NTX) modulates neural and behavioral responses to opioid cues, as well as resting-state brain connectivity.

METHODS

Thirty male patients with moderate-severe OUD underwent fMRI during an opioid-versus-neutral image task at baseline and after 2 weeks of oral-NTX treatment. The DDQ and OCDUS were administered for craving assessment. Task fMRI data was analyzed with linear mixed-effects models (3dLME). Resting-state fMRI was analyzed for ROI-to-ROI functional connectivity changes in key craving-related regions.

RESULTS

Oral_NTX significantly reduced both DDQ and OCDUS scores (p<0.01). Task-based fMRI revealed significant reductions in cue-induced activation in the anterior cingulate cortex (ACC) and cerebellum (whole-brain p<0.05, cluster-corrected). ROI analyses confirmed pre-to-post decreases in ACC and cerebellar activation (t>3.5, p<0.05). Larger craving reductions correlated with greater left superior temporal deactivation (t≈1.97, p<0.05). Resting-state connectivity analysis showed significant attenuation of intrinsic functional coupling between ACC-insula, nucleus accumbens (NAc)-amygdala, and cerebellum-hippocampus (p<0.05). These decreases complement task findings, indicating widespread dampening of salience and reward network interactions following oral-NTX.

CONCLUSION

Oral-NTX reduces cue-driven activation in cortical and cerebellar regions while dampening resting-state connectivity within craving circuits.