Every explanation of ADHD you have ever read talks about dopamine. A post going around this week says something different: ADHD may also be a problem of GABA, the signal that tells neurons to slow down. For once, the post is accurate. It summarises a 2024 review in Neuropharmacology by Anthony Ferranti, Deborah Luessen and Colleen Niswender at Vanderbilt University, and the review is worth reading carefully, including the parts the post leaves out.
Accelerator and Brake
Your cortex runs on two opposite signals. Glutamate excites neurons, GABA inhibits them. Neuroscientists call the ratio between the two the excitation/inhibition balance, and a great deal of what the brain does well, focusing on one thing, ignoring the rest, stopping an action already started, depends on the brake being applied at the right place and the right moment. Most ADHD research has looked at the accelerator side, dopamine and noradrenaline, which is what stimulant medication acts on. The review asks what happens when you look at the brake.
What Brain Imaging Found
GABA can be measured in a living brain with magnetic resonance spectroscopy, a variant of MRI that reads chemical concentrations in a small region. Several studies have used it in ADHD, and the picture is honest rather than tidy.
In children aged 8 to 12, GABA was lower in the somatosensory and motor cortex than in controls (Edden, 2012). In children aged 5 to 9, GABA was lower in the striatum, and the lower it was, the poorer the child's ability to stop a response (Puts, 2020). In adult women with ADHD, GABA was lower in the anterior cingulate cortex, a region central to attention and self-control, and the lower level went with more inattention (Ende, 2016).
But the same Puts study found no difference in the anterior cingulate, the dorsolateral prefrontal cortex or the premotor cortex. And one adult study found the opposite, higher GABA in adults with ADHD and no difference in children (Bollmann, 2015). The authors write it plainly: low GABA in ADHD "may be specific to subregions of the cortex", and the inconsistencies "warrant further investigation". The brake is involved. Where, and in whom, is not settled.
The Genes
Genetic studies point the same way. Variants in GAD1, the gene for the enzyme that makes GABA, are associated with ADHD, particularly the hyperactive-impulsive side. GAD1 and COMT together influence how much GABA the anterior cingulate contains. CDH13, one of the most replicated ADHD risk genes, is needed for the inhibitory interneurons to work properly. GRM5 and GRM7, which code for two glutamate receptors that sit on those interneurons, have "repeatedly been shown to be mutated" in ADHD cohorts. ELFN1, which anchors one of those receptors at the synapse, is linked to ADHD, epilepsy and Tourette syndrome at once, which fits how often these conditions travel together.
Two cautions. Each of these variants has a tiny effect, and none of them is a test for ADHD; we explain why in our article on ADHD DNA tests. And several of them are not "GABA genes" at all: they are glutamate receptors on GABA neurons, a reminder that accelerator and brake are the same circuit seen from two sides.
Why This Matters: The 30%
The review opens with a number that gets little attention: "approximately 30% of ADHD patients do not respond to stimulant treatments." Stimulants act on dopamine and noradrenaline. If the brake is part of the problem in some people, a drug that works only on the accelerator will not help them, and a different kind of medication might.
That is what the authors propose. Not GABA itself, which does not cross into the brain in useful amounts, but molecules that tune the receptors on the inhibitory neurons: positive modulators of the mGlu5 receptor (one, VU0409551, corrected stress-induced attention deficits in animals), of the mGlu1 receptor (VU6004909 restored working memory in a model of the disorder), and approaches that target specific families of interneurons. Chemogenetic activation of two of those families improved attention, impulsivity and hyperactivity in mice. All of this is preclinical. None of it is in a pharmacy, and the honest timeline is years.
What It Does Not Mean
It does not mean you should buy GABA capsules. Oral GABA barely reaches the brain, and the supplement claims built on the GAD1 gene are examined in our GABA and glutamate fact-check. It does not replace dopamine: the authors themselves say it is unclear whether GABA changes come before or after the dopamine changes in development, and that the balance "may shift over the course of development, as well as day-to-day". And it does not make ADHD a "chemical imbalance" you can measure in a blood test. It makes it what the evidence has said for a while: a difference in how whole circuits regulate themselves, with several entry points for treatment rather than one. Our article on the "low dopamine" myth and the one on serotonin in ADHD tell the other two parts of that story.
What You Can Do Today
If attention, impulsivity or restlessness have been a question for you, start with a validated screening: our free ADHD test (ASRS v1.1) takes ten minutes and gives you a score you can bring to a clinician. If stimulants have not worked for you or for your child, that is not a dead end; it is precisely the group this research is trying to reach, and non-stimulant options already exist that a psychiatrist can discuss. And because the brake also depends on sleep, our article on local sleep in ADHD is the natural next read.
Sources: Ferranti AS, Luessen DJ, Niswender CM (2024). Novel pharmacological targets for GABAergic dysfunction in ADHD. Neuropharmacology 249:109897 (open access on PubMed Central); Edden RA et al. (2012), Archives of General Psychiatry; Bollmann S et al. (2015), Translational Psychiatry; Ende G et al. (2016), Neuropsychopharmacology; Puts NA et al. (2020), Journal of Neurodevelopmental Disorders; Faraone SV et al. (2015), Nature Reviews Disease Primers.