Targeting neuroinflammation with minocycline in heavy drinkers

Psychopharmacology (Berl). 2019 Oct;236(10):3013-3021. doi: 10.1007/s00213-019-05205-3. Epub 2019 Mar 27.

Abstract

Rationale: Alcohol has both acute and chronic effects on neuroimmune signaling, including triggering pro-inflammatory cytokine release by microglia. Minocycline, a second-generation tetracycline antibiotic, inhibits microglial activation and reduces neuroinflammation in preclinical studies. In mice, minocycline also reduces ethanol intake, attenuates ethanol-induced conditioned place preference, and inhibits ethanol-induced microglial activation and pro-inflammatory cytokine release.

Objective: Here, for the first time, we tested the effects of minocycline on subjective response to ethanol and acute ethanol-induced inflammation in humans.

Methods: Forty-eight heavy drinkers participated in a double-blind, placebo-controlled trial in which they were randomized to receive placebo, 100 mg, or 200 mg of minocycline for 10 days. Each subject then underwent two experimental sessions in which they were given a fixed dose of intravenous ethanol using a "clamp" procedure (100 mg%) or placebo (normal saline) on days 8 and 10 of treatment.

Results: Minocycline was well tolerated, but there was no effect of either dose of minocycline on subjective response to ethanol or ethanol-induced craving; minocycline effects on cognitive function seem to interact with age. Minocycline treatment did not alter serum cytokine levels at baseline or during ethanol-exposure, although certain baseline cytokine levels predict sedative response to ethanol.

Conclusion: These findings indicate that a short-term treatment with minocycline may not alter ethanol-related inflammation or subjective response to ethanol in humans. Further research is needed to identify pharmacological agents with robust effects on ethanol-induced inflammation to determine whether neuroimmune modulation represents a viable treatment strategy for alcohol use disorder.

Keywords: Alcoholism; Craving; Cytokines; Ethanol; Inflammation; Minocycline.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Alcoholic Intoxication / drug therapy*
  • Alcoholic Intoxication / immunology
  • Alcoholic Intoxication / metabolism
  • Alcoholism / drug therapy*
  • Alcoholism / immunology
  • Alcoholism / metabolism
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Double-Blind Method
  • Drug Delivery Systems / methods*
  • Ethanol / administration & dosage*
  • Humans
  • Infusions, Intravenous
  • Male
  • Mice
  • Microglia / drug effects
  • Microglia / immunology
  • Microglia / metabolism
  • Middle Aged
  • Minocycline / administration & dosage*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • Ethanol
  • Minocycline