Minocycline does not affect experimental pain or addiction-related outcomes in opioid maintained patients

  • Caroline A. Arout
  • Andrew J. Waters
  • R. Ross MacLean
  • Peggy Compton
  • Mehmet Sofuoglu
Original Investigation



Minocycline, a tetracycline antibiotic, inhibits activation of microglia. In preclinical studies, minocycline prevented development of opioid tolerance and opioid-induced hyperalgesia (OIH). The goal of this study was to determine if minocycline changes pain threshold and tolerance in individuals with opioid use disorder who are maintained on agonist treatment.


In this double-blind, randomized human laboratory study, 20 participants were randomized to either minocycline (200 mg/day) or placebo treatment for 15 days. The study had three test sessions (days 1, 8, and 15 of treatment) and one follow-up visit 1 week after the end of treatment. In each test session, participants were assessed on several subjective and cognitive measures, followed by assessment of pain sensitivity using the Cold Pressor Test (CPT). Daily surveys and cognitive measures using Ecological Momentary Assessment (EMA) were also collected four times a day on days 8 through 14 of treatment, and proinflammatory serum cytokines were assessed before and on the last day of treatment.


Minocycline treatment did not change pain threshold or tolerance on the CPT. Similarly, minocycline did not change severity of pain, opioid craving, withdrawal, or serum cytokines. Minocycline treatment increased accuracy on a Go/No-Go task.


While these findings do not support minocycline’s effects on OIH, minocycline may have a potential use as a cognitive enhancer for individuals with opioid use disorder, a finding that warrants further systematic studies.


Opioid Hyperalgesia EMA Microglia Minocycline 



This study was conducted during Dr. Arout’s postdoctoral fellowship at Yale University School of Medicine (NIDA T32 DA007238; Principal Investigator: I. L. Petrakis) and was supported by the VA New England Mental Illness Research, Education and Clinical Center (MIRECC). We would like to thank Dr. Lesley Devine of Yale University School of Medicine for executing the serum cytokine analysis.

Compliance with ethical standards

Conflicts of interest

The authors declare that there is no conflict of interest.

Supplementary material

213_2018_5146_MOESM1_ESM.docx (20 kb)
ESM 1 (DOCX 20 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PsychiatryYale University School of MedicineWest HavenUSA
  2. 2.Department of Psychiatry, New York State Psychiatric InstituteColumbia University Irving Medical CenterNew YorkUSA
  3. 3.Department of Medical and Clinical PsychologyUniformed Services University of the Health SciencesBethesdaUSA
  4. 4.Veterans Health Administration Mental Illness Research, Education, and Clinical Center (MIRECC)VA Connecticut Healthcare SystemWest HavenUSA
  5. 5.Department of Family and Community HealthUniversity of Pennsylvania School of NursingPhiladelphiaUSA

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