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Engaging Gut-to-Brain Signalling to Treat Alcohol Use Disorder.

Paula L Hoffman1,2, Giordano de Guglielmo3, Valentina Vengeliene4

  • 1Lohocla Research Corporation, Aurora, Colorado, USA.

Addiction Biology
|March 25, 2026
PubMed
Summary
This summary is machine-generated.

A new drug, Nezavist, shows promise for treating alcohol use disorder (AUD). It reduces relapse in animal models by acting outside the central nervous system, potentially offering a novel therapeutic approach.

Keywords:
AUDNTS activationNezavistgut–brain signallinghippocampal inflammatory mediatorsperipheral inflammationvagal activation

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Gastroenterology

Background:

  • Alcohol use disorder (AUD) affects millions, with limited effective medication options.
  • Current AUD treatments have variable efficacy and low adoption rates.
  • Chronic alcohol use poses significant health and economic burdens.

Purpose of the Study:

  • To investigate Nezavist, a novel small molecule, as a potential medication for AUD.
  • To explore Nezavist's mechanism of action, particularly its peripheral effects.
  • To provide evidence supporting Nezavist's efficacy in reducing alcohol relapse.

Main Methods:

  • Studied Nezavist's effects on alcohol consumption in established animal models of alcohol dependence.
  • Conducted pharmacokinetic analysis to determine Nezavist's distribution.
  • Hypothesized and investigated a gut-brain axis mechanism involving the vagus nerve.

Main Results:

  • Nezavist significantly reduced relapse to chronic alcohol consumption in animal models.
  • Pharmacokinetic studies confirmed Nezavist does not enter the central nervous system (CNS).
  • Evidence suggests Nezavist stimulates vagal afferents from the intestine, potentially reducing brain inflammation and alcohol craving.

Conclusions:

  • Nezavist demonstrates potential as a novel therapeutic agent for AUD.
  • The drug's efficacy appears mediated by a peripheral gut-brain pathway, not direct CNS action.
  • Further research is warranted to confirm Nezavist's mechanism and clinical utility for addiction treatment.