Altered GABAB receptor sensitivity in heavy drinkers indexed using a TMS-based biomarker: a randomized controlled experimental medicine trial

Published October 23, 2026. A TMS measure of cortical inhibition responded differently to a higher baclofen dose in heavy and light drinkers, suggesting a possible biomarker of altered GABAB-receptor sensitivity. The study tested physiology in a small volunteer sample, not a treatment for alcohol use disorder.

Montemitro C, Donahue D, Costumati A, Maruottolo F, Terezza S, Sjoberg C, Perini I, Roman M, Kugelberg FC, Heilig M.
Translational Psychiatry · Publication date: 2026-10-23
Added to site: 2026-10-24
DOI: 10.1038/s41398-026-04530-4

Published October 23, 2026. Added to Neurofeedback.com October 24, 2026.

Modalities

TMS, Paired-pulse TMS, Biomarkers

Clinical focus

Heavy alcohol use, GABAB receptors, Cortical inhibition

Population

Healthy volunteers categorized as heavy or light drinkers

Sample

31 participants: 16 heavy drinkers and 15 light drinkers

Intervention / method

Participants received baclofen 30 mg, baclofen 60 mg and placebo across three sessions; paired-pulse TMS measured cortical inhibition and facilitation before and about 60 minutes after dosing, alongside baclofen levels and growth hormone

Comparator

Within-participant baclofen doses versus placebo and between-group heavy- versus light-drinker response patterns

Clinician summary

Baclofen increased growth hormone in a dose-dependent manner. Long-interval intracortical inhibition was potentiated at 30 and 60 mg in light drinkers, while heavy drinkers showed potentiation at 30 mg but not 60 mg despite comparable pharmacokinetics. Short-interval intracortical inhibition and corticospinal excitability showed no consistent modulation.

How to interpret the findings

The study included only 31 volunteers and compared heavy with light drinkers rather than enrolling a treatment-seeking alcohol-use-disorder cohort. The physiological endpoint is a candidate biomarker, not a validated clinical test, predictor of treatment response or demonstration of benefit. The abstract does not provide complete effect sizes, confidence intervals, adverse-event detail or long-term follow-up.

Equipment and disclosures

Paired-pulse TMS was used to measure long- and short-interval intracortical inhibition and facilitation. The checked abstract does not identify a device manufacturer, and no equipment is attributed to BrainMaster.

Supported by the Knut and Alice Wallenberg Foundation and the Swedish Research Council. One author reported consulting fees, research support or other compensation from Indivior, Nordic Drugs, Camurus, BrainsWay, Aelis Farma and Janssen Pharmaceuticals; the other authors reported no biomedical financial interests or potential conflicts. No indexed correction, retraction or expression-of-concern relation appeared in the retained PubMed or Crossref records; this is a bounded check. AI-assisted source review.

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