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Prefrontal cortex response to drug cues, craving, and current depressive symptoms are associated with treatment outcomes in methadone-maintained patients

Neuropsychopharmacologyvolume 44pages826833 (2019) | Download Citation


Methadone maintenance is an effective treatment for opioid use disorder, yet many methadone-maintained patients (MMPs) continue to struggle with chronic relapse. The current study evaluated whether functional near-infrared spectroscopy (fNIRS) could identify prefrontal cortex (PFC) markers of ongoing opioid use in MMPs, and whether clinical measures of depression and self-report measures of craving would also be associated with opioid use. MMPs (n = 29) underwent a drug cue reactivity paradigm during fNIRS measurements of PFC reactivity. Self-reported opioid craving (measured by a visual analog scale; 0–100) was collected before and after drug cue reactivity, and depressive symptoms were assessed via the 17-item Hamilton Depression Rating Scale (HAM-D). Hierarchical regression and partial correlations were used to evaluate associations between weekly urine drug screens over a 90-day follow-up period and fNIRS, craving, and HAM-D assessments. Neural response to drug cues in the left lateral PFC, controlling for age, sex, and days in treatment was significantly associated with percent opioid-negative urine screens during follow-up (∆F1, 24 = 13.19, p = 0.001, ∆R2 = 0.30), and correctly classified 86% of MMPs as either using opioids, or abstaining from opioids (χ2(4) = 16.28, p = 0.003). Baseline craving (p < 0.001) and HAM-D assessment (p < 0.01) were also associated with percent opioid-negative urine screens. Combining fNIRS results, baseline craving scores, and HAM-D scores created a robust predictive model (∆F3, 22 = 16.75, p < 0.001, ∆R2 = 0.59). These data provide preliminary evidence that the fNIRS technology may have value as an objective measure of treatment outcomes within outpatient methadone clinics. Depressive symptoms and drug craving were also correlated with opioid use in MMPs.

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We thank Kori Kindbom and her clinical research support team for their help in conducting this study, and the Addiction Treatment Services program patients whose participation made it possible.

Author information


  1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224, USA

    • Andrew S. Huhn
    • , Mary M. Sweeney
    • , Robert K. Brooner
    • , Michael S. Kidorf
    • , D. Andrew Tompkins
    •  & Kelly E. Dunn
  2. Department of Psychiatry, University of California San Francisco School of Medicine, San Francisco, CA, USA

    • D. Andrew Tompkins
  3. School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA

    • Hasan Ayaz
  4. Department of Family and Community Health, University of Pennsylvania, Philadelphia, PA, USA

    • Hasan Ayaz
  5. Division of General Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    • Hasan Ayaz


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Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The remaining authors declare no competing interests.

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Correspondence to Andrew S. Huhn.

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