Key Takeaways
- A randomized study involving 31 adults found that heavy drinkers responded differently to a higher dose of baclofen, an inexpensive generic muscle relaxant used for decades.
- At 30 milligrams, baclofen significantly increased a measure of brain inhibition in both heavy and light drinkers. At 60 milligrams, the increase remained statistically significant in light drinkers but not in heavy drinkers.
- Researchers did not detect a significant difference in blood baclofen concentrations between the groups, although this does not establish identical drug exposure.
- Baclofen has established medical uses and has previously been investigated for alcohol use disorder. This study did not test whether it reduces drinking, cravings, or relapse.
- The findings may help researchers investigate differences in brain signaling associated with heavy alcohol consumption. They do not establish that alcohol caused those differences.
Introduction
Researchers found differences in how heavy and light drinkers responded to baclofen, a decades-old muscle relaxant, in a small randomized study measuring brain inhibition.
A cheap muscle relaxant that has been prescribed for decades has revealed an unexpected difference in how heavy and light drinkers respond to a medication that affects brain signaling.
The drug, baclofen, is commonly used to relieve muscle spasticity associated with neurological conditions. Scientists have also investigated whether it could help people with alcohol use disorder, although clinical results have been mixed.
Now, a randomized experiment published October 23, 2026, in Translational Psychiatry has used baclofen for a different purpose: to investigate how alcohol consumption patterns are associated with the brain’s response to inhibitory signaling.
Researchers studied 31 adults and found that both heavy and light drinkers showed a measurable increase in cortical inhibition after a lower dose of baclofen. At a higher dose, the response differed between groups.
The difference remained after researchers accounted for measured blood concentrations of the medication.
The discovery does not mean baclofen improved brain health or treated alcohol dependence. Instead, it offers a potential method for investigating biological differences that may be relevant to the development of alcohol use disorder.
What Is Baclofen, and Why Are Scientists Studying It?
Baclofen is an established prescription medication that has been used since the 1970s. It is available in generic formulations and is generally inexpensive.
Its main medical use is treating muscle spasticity, including spasticity associated with multiple sclerosis and spinal cord injuries.
The medication works by activating gamma-aminobutyric acid type B receptors, commonly called GABA-B receptors.
These receptors help regulate nerve-cell activity by reducing certain types of neuronal signaling.
Because GABA signaling is involved in brain circuits associated with alcohol use, researchers have investigated whether medications acting on these receptors might help treat alcohol use disorder.
Some clinical trials of baclofen have reported improvements in alcohol-related outcomes, while others have found limited or inconsistent benefits.
Baclofen is not approved by the US Food and Drug Administration to treat alcohol use disorder.
The new study was not designed to resolve whether baclofen works as an addiction treatment. Instead, the researchers used it as a pharmacological tool to investigate how the brain responds when GABA-B receptors are activated.
That distinction is central to understanding the findings.
What the Study Examined
Researchers from Linköping University in Sweden and collaborating institutions conducted a randomized, double-blind, placebo-controlled crossover experiment.
The final analysis included 31 adults:
- 16 heavy drinkers
- 15 light drinkers
The participants were generally young and healthy. The average age was approximately 24 years among heavy drinkers and 28 years among light drinkers.
Heavy drinkers reported consuming an average of 14.91 standard drinks per week, compared with 4.39 among light drinkers.
The researchers classified drinking patterns using sex-specific Swedish thresholds and other indicators of risky drinking.
Importantly, participants with moderate or severe alcohol use disorder were excluded. The experiment therefore did not directly examine patients receiving treatment for alcohol dependence.
Each participant attended three experimental sessions, separated by at least seven days.
During those sessions, participants received a single dose of 30 milligrams of baclofen, 60 milligrams of baclofen, or a matching placebo.
The order was randomized, and both participants and outcome assessors were blinded to the treatment administered.
Researchers then used transcranial magnetic stimulation, or TMS, to measure activity in the motor cortex.
Their main measurement was long-interval intracortical inhibition, abbreviated LICI.
LICI provides an indirect measure of inhibitory signaling associated with GABA-B receptor activity. In simple terms, it helps researchers assess how strongly certain brain circuits suppress nerve signals in response to stimulation. It is a laboratory measurement of motor-cortex activity, not a test of intelligence, memory, or overall brain health.
The researchers also measured blood concentrations of baclofen and growth hormone release to investigate whether differences in drug exposure or other biological responses could explain the results (Montemitro et al., 2026).
What Researchers Found
The Lower Dose Increased Brain Inhibition in Both Groups
At 30 milligrams, baclofen significantly increased the measured inhibitory response in both heavy and light drinkers.
The researchers reported statistically significant changes among light drinkers (p = 0.005) and heavy drinkers (p = 0.043).
This indicated that the lower dose activated the relevant inhibitory pathway in both groups.
However, the results changed when researchers examined the higher dose.
Heavy Drinkers Showed a Different Response at 60 Milligrams
At 60 milligrams, light drinkers showed a statistically significant increase in the measured cortical inhibition (p = 0.014).
Among heavy drinkers, the researchers did not detect a statistically significant increase (p = 0.73).
The difference between groups at this dose was statistically significant (p = 0.003).
The researchers also reported a significant interaction between drinking group, treatment, and measurement time in their prespecified analysis (p = 0.042).
These findings indicate that the measured response to baclofen differed according to participants’ drinking patterns.
Importantly, the lack of a statistically significant increase among heavy drinkers does not prove that the medication had no physiological effect.
The study involved a small sample and assessed a specific measure of motor-cortex inhibition rather than overall brain function.
The results therefore support a difference in measured responsiveness, not a conclusion that heavy drinkers’ brains stopped responding to baclofen.
Blood Drug Levels Did Not Explain the Observed Difference
Researchers measured blood concentrations of baclofen to investigate whether differences in drug exposure might account for the results.
Baclofen concentrations generally increased with dose, as expected.
The researchers did not detect a statistically significant overall difference in blood drug concentrations between heavy and light drinkers.
Additional analyses accounting for measured blood concentrations did not eliminate the observed difference in cortical inhibition.
These findings suggest that differences in physiological responsiveness may be more relevant than differences in systemic drug exposure.
However, a nonsignificant comparison does not establish that drug exposure was identical between groups.
Blood concentrations also cannot directly determine how much baclofen reached specific brain regions or how individual receptors responded.
The results therefore support, but do not conclusively establish, the interpretation that the groups differed in their sensitivity to GABA-B receptor activation.
The Higher Dose Produced Different Changes in Cortical Inhibition
An additional analysis accounted for differences in participants’ baseline inhibitory measurements.
At 60 milligrams, the estimated change in LICI was:
| Group | Estimated change |
|---|---|
| Light drinkers | −10.69 percentage points |
| Heavy drinkers | +3.39 percentage points |
In this measurement, a negative change indicated stronger inhibition because researchers expressed LICI as the remaining muscle response after a conditioning magnetic pulse.
The values describe changes in a laboratory measure, not the percentage of brain function lost or gained.
They also do not establish that one group’s brain function was healthier than the other’s.
Hormonal Responses Were Largely Preserved
Researchers also measured growth hormone release, another biological response associated with GABA-B receptor activation.
Both groups showed hormonal responses to baclofen, although their timing differed somewhat.
Unlike the motor-cortex measurement, growth hormone responses did not show the same clear separation between heavy and light drinkers.
This matters because the two measurements reflect different biological processes.
Growth hormone release provides information about neuroendocrine signaling, while LICI measures inhibitory activity in the motor cortex.
The findings indicate that these responses are not interchangeable.
Has Baclofen Helped People With Alcohol Dependence Before?
Baclofen has been investigated as a possible treatment for alcohol use disorder for years.
The idea is that activating GABA-B receptors might influence brain pathways involved in alcohol reinforcement and related behaviors.
Some clinical trials have reported benefits, including improvements in certain abstinence-related outcomes. Other studies have not found consistent improvements.
As a result, baclofen remains a debated treatment option rather than an established, universally effective therapy for alcohol use disorder.
The new study adds information about how people with different drinking patterns respond biologically to the drug, but it does not provide evidence of clinical benefit.
Participants were not followed to determine whether baclofen reduced their alcohol consumption.
Researchers also did not establish whether the medication reduced cravings, prevented relapse, or improved psychological functioning.
The study’s results therefore cannot be used to recommend baclofen as a treatment for heavy drinking.
How the Findings Compare With Earlier Research
Previous Research Also Identified Altered Baclofen Responses
A 2018 study investigated responses to baclofen in 12 healthy male volunteers and eight men with alcohol dependence who had been abstinent for at least four weeks.
Researchers measured blood concentrations of baclofen, growth hormone release, and participants’ subjective responses to the medication.
At a 60-milligram dose, men with alcohol dependence showed weaker growth hormone and subjective responses than healthy controls, despite no statistically significant differences in measured pharmacokinetic parameters (Durant et al., 2018).
However, the groups differed in characteristics such as age and drinking history, and the study used different dosing schedules and blinding procedures across groups.
The results therefore require cautious interpretation.
The 2026 experiment examined a different population: heavy drinkers who did not have moderate or severe alcohol use disorder.
It also used transcranial magnetic stimulation to investigate a specific measure of motor-cortex inhibition.
Both studies identified differences in baclofen-related responses that were not readily explained by measured blood drug concentrations.
However, the hormonal findings differed.
The 2018 study reported markedly reduced growth hormone responses among men with alcohol dependence. The 2026 study reported largely preserved hormonal responses among heavy drinkers.
These differences may reflect participant characteristics, alcohol exposure, or other factors.
Neither study establishes that alcohol consumption caused the observed physiological differences.
What the Findings May Mean
A Potential Way to Investigate Early Brain Changes
One possibility raised by the study is that differences in GABA-B receptor-related signaling may be detectable before someone develops severe alcohol-related problems.
That would be scientifically important because researchers are interested in identifying biological changes associated with the progression from heavy drinking to alcohol use disorder.
However, the study cannot determine whether the observed differences developed because of alcohol consumption.
People who drink heavily may differ from light drinkers in biological characteristics that existed before their drinking patterns developed.
The experiment also did not establish whether the altered response would improve if participants reduced their alcohol consumption or stopped drinking.
Longitudinal studies following people over time would be needed to answer those questions.
Could an Old Drug Help Develop Better Treatments?
The potential value of baclofen in this research lies partly in its ability to activate a well-defined biological target.
Scientists developing medications for alcohol use disorder need ways to determine whether a drug reaches its intended target and produces the expected physiological response.
The study indicates that LICI measurements obtained through transcranial magnetic stimulation could help investigate such responses.
This might eventually support research into medications targeting GABA-B signaling.
However, a laboratory biomarker is not the same as a demonstrated treatment benefit.
Before such measurements could guide clinical care, researchers would need to establish whether they reliably predict meaningful outcomes, such as reduced drinking or sustained recovery.
A Higher Dose Is Not Necessarily Better
The findings demonstrate why increasing a medication dose does not always produce a straightforward increase in a measured biological effect.
In this experiment, heavy drinkers showed increased cortical inhibition after 30 milligrams of baclofen, but researchers did not detect the same statistically significant response after 60 milligrams.
This does not establish that a lower dose is clinically preferable or that a higher dose would be ineffective for treating alcohol use disorder.
The study was not designed to compare treatment strategies or evaluate clinical benefits.
Baclofen can cause drowsiness, dizziness, weakness, and impaired coordination. Alcohol may intensify some of these effects, increasing safety concerns.
Abruptly stopping baclofen after ongoing use can also cause serious withdrawal symptoms, including confusion, hallucinations, and seizures.
People should not use baclofen to self-treat heavy drinking or alcohol dependence, and anyone already taking the medication should consult their prescribing clinician before changing the dose or stopping treatment.
Limitations
The study’s main limitation was its small sample size.
Only 31 participants were included in the final analysis. Although the researchers planned the sample size around the primary brain measurement, the experiment was not large enough to reliably investigate smaller effects or differences across many population subgroups.
Participants were also generally young and healthy.
The findings may not apply to older adults, people with significant medical conditions, or patients with diagnosed alcohol use disorder.
Another limitation was the measurement of alcohol exposure.
The researchers classified participants using recent drinking patterns and indicators of risky drinking, but lifetime alcohol exposure was not systematically measured.
Consequently, the study could not determine whether the duration of heavy drinking influenced the observed response.
There was also considerable individual variability in baseline brain measurements.
Factors such as sleep, stress, mood, recent substance exposure, and ordinary measurement variability can influence TMS results.
Although the researchers standardized several testing conditions and conducted additional statistical adjustments, residual variability remained possible.
Most importantly, drinking history was not randomized.
Participants were randomly assigned to receive baclofen or placebo in different sessions, but they were not randomly assigned to become heavy or light drinkers.
Therefore, the experiment can support conclusions about short-term responses to the administered drug, but it cannot establish that heavy alcohol consumption caused the differences between groups.
Finally, the study measured biological responses over a short period following single doses.
It did not investigate long-term brain changes, drinking behavior, addiction treatment outcomes, or whether the observed differences persist during abstinence.
Final Thoughts
Baclofen is neither new nor expensive. It is a long-established generic medication used to treat muscle spasticity.
What makes the latest study interesting is not a newly discovered treatment benefit, but the different way heavy drinkers responded to the medication.
In a randomized experiment involving 31 adults, both heavy and light drinkers showed increased cortical inhibition after a 30-milligram dose.
At 60 milligrams, the increase remained statistically significant among light drinkers, while researchers did not detect a significant increase among heavy drinkers.
The difference between groups remained evident after accounting for measured blood drug concentrations.
The results provide evidence of a difference in short-term physiological responsiveness associated with drinking patterns.
They do not prove that alcohol caused the difference, that it represents permanent brain damage, or that baclofen can treat alcohol dependence.
The research may ultimately be useful in developing better ways to investigate brain signaling and evaluate medications targeting GABA-B receptors.
For now, its significance is in what an old drug may reveal about the brain, rather than what it has been shown to treat.
Funding and Disclosures
The study was supported by a contract with Indivior, a pharmaceutical company, and grants from the Swedish Research Council and the Wallenberg Foundation awarded to Markus Heilig.
The authors stated that the funding sources had no role in study design, data collection, analysis, interpretation, manuscript preparation, or the decision to submit the research for publication.
Open-access publication funding was provided by Linköping University.
Markus Heilig disclosed 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 of interest.
References
Durant, C. F., Paterson, L. M., Turton, S., Wilson, S. J., Myers, J. F. M., Muthukumaraswamy, S., Venkataraman, A., Mick, I., Paterson, S., Jones, T., Nahar, L. K., Cordero, R. E., Nutt, D. J., & Lingford-Hughes, A. (2018). Using baclofen to explore GABA-B receptor function in alcohol dependence: Insights from pharmacokinetic and pharmacodynamic measures. Frontiers in Psychiatry, 9, Article 664. https://doi.org/10.3389/fpsyt.2018.00664
Montemitro, C., Donahue, D., Costumati, A., Maruottolo, F., Terezza, S., Sjoberg, C., Perini, I., Roman, M., Kugelberg, F. C., & Heilig, M. (2026). Altered GABA-B receptor sensitivity in heavy drinkers indexed using a TMS-based biomarker: A randomized controlled experimental medicine trial. Translational Psychiatry, 16, Article 582. https://doi.org/10.1038/s41398-026-04530-4
