Preclinical studies have shown effects of chronic exposure to addictive drugs on glutamatergic‐mediated neuroplasticity in frontostriatal circuitry. These initial findings have been paralleled by human functional magnetic resonance imaging (fMRI) research demonstrating weaker frontostriatal resting‐state functional connectivity (rsFC) among individuals with psychostimulant use disorders. We hypothesized that prescription opioid users with chronic pain, as compared with healthy control subjects, would evidence weaker frontostriatal rsFC coupled with less frontostriatal gray matter volume (GMV).