Alcohol: brain response to baclofen differs in heavy drinkers

A trial designed to measure a biological response

The researchers included 16 heavy drinkers and 15 light drinkers, described as healthy volunteers. Each participant received 30 mg of baclofen, 60 mg of baclofen or a placebo across three sessions. The trial was randomized, double-blind and crossover: each person took part in the different conditions.

Before administration and then approximately 60 minutes afterwards, the researchers used transcranial magnetic stimulation to measure several cortical responses. Their main indicator was long-interval intracortical inhibition, or LICI, used here as a marker of GABA-B receptor function. They also measured blood concentrations of baclofen and growth hormone.

A difference at the highest experimental dose

In light drinkers, baclofen increased LICI at 30 mg, with a similar response at 60 mg. The authors suggest this may indicate a plateau. In heavy drinkers, the increase was comparable at 30 mg but was no longer observed at 60 mg, despite comparable pharmacokinetics between the groups.

This difference suggests an altered response to stronger stimulation of GABA-B receptors. It does not mean that all brain inhibition is reduced: the other measures showed no consistent modulation, notably for short-interval intracortical inhibition and corticospinal excitability.

Baclofen also increased growth hormone release in a dose-dependent manner. This neuroendocrine signal provides an additional measure of its biological action, not evidence of clinical benefit.

An avenue for research, not a basis for choosing treatment

The main value is methodological: these measures could help researchers study the action of treatments targeting GABA-B receptors. However, the trial demonstrates no reduction in alcohol consumption, desire to drink or risk of relapse.

Randomization concerned the administration of baclofen and placebo, not habitual alcohol consumption. It therefore does not allow the difference between groups to be attributed to alcohol. The abstract also does not specify the thresholds defining heavy and light drinkers. These experimental doses are not recommendations for use.

What we can take away

This small trial identifies a difference in biological response to baclofen depending on alcohol consumption. It opens up an avenue for measurement, without providing a basis for choosing a treatment or dose.