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

Abstract

Rationale

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

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.

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Correspondence to Caroline A. Arout.

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Arout, C.A., Waters, A.J., MacLean, R.R. et al. Minocycline does not affect experimental pain or addiction-related outcomes in opioid maintained patients. Psychopharmacology 236, 2857–2866 (2019). https://doi.org/10.1007/s00213-018-5146-7

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Keywords

  • Opioid
  • Hyperalgesia
  • EMA
  • Microglia
  • Minocycline