Overview
A new 2026 study measured cortisol, thyroid hormones, and seven inflammatory markers in 40 medication-naive adolescents with ADHD compared to 41 healthy controls, then re-measured the ADHD group after four months of methylphenidate.
Adolescents with ADHD had significantly lower morning cortisol and significantly higher levels of multiple inflammatory markers, both pro- and anti-inflammatory. Medication improved ADHD symptoms in ~75% of participants but didn’t affect inflammation markers or cortisol levels.
This non-causal research suggests that while stimulant medication helps behavior, it may not help with underlying metabolic issues. Coupling medication with behavioral interventions like nervous system regulation and nutrition may be key in improving those measures.
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Study Design
Aguado-Rivas, Checa-Ros, Fernández-López et al. (2026) recruited 80 adolescents from a primary health center in Granada, Spain — all medication-naive at the start. The ADHD group (n = 40) was assessed at baseline and again after approximately four months of methylphenidate (MPH) treatment. The control group (n = 41) was assessed once.
Morning fasting blood samples were taken for cortisol, TSH (thyroid-stimulating hormone), DHEAS (dehydroepiandrosterone sulphate — an adrenal hormone that tends to have anti-stress effects), S100B protein (a marker linked to neuroinflammation), and seven cytokines: IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, and TNF-α.
Cortisol Levels Were Lower in ADHD
Cortisol levels were significantly lower in adolescents with ADHD compared to controls (9.5 vs. 15.81 mg/mL).
Both groups fell within the normal clinical reference range — so this isn’t a cortisol deficiency in a medical sense, but it is significantly lower than “normal”. To learn more about the other research on ADHD and cortisol, read The Complex Relationship Between Cortisol and ADHD.
Importantly, four months of MPH didn’t meaningfully change cortisol levels. This tracks with other research we have on ADHD, cortisol, and stimulant medication (How ADHD Medication Affects Cortisol).
TSH Levels Were Higher in ADHD kids with ODD
TSH was slightly higher in the ADHD group, but only reached significance in those who also had ODD (oppositional defiant disorder) symptoms.
DHEAS and S100B showed no significant differences between groups.
Overall, ADHD symptoms improved significantly for most participants (~75%), but the neuroendocrine profile stayed essentially unchanged.
Inflammatory Markers Were Higher In ADHD
Adolescents with ADHD showed significantly higher concentrations of multiple cytokines: both pro-inflammatory and anti-inflammatory.
- IL-1β (pro-inflammatory): significantly higher in ADHD, especially in males (p < 0.009)
- IL-5: significantly higher in ADHD males (p < 0.002)
- IL-6 (pro-inflammatory): significantly higher across the group (p < 0.0002)
- IL-4 (anti-inflammatory): significantly higher, particularly in males (p < 0.0009)
- IL-10 (anti-inflammatory): significantly higher (p < 0.0000)
- IL-13: significantly higher (p < 0.022)
- TNF-α: no significant difference
Since both pro- and anti-inflammatory markers are elevated, this doesn’t look like simple inflammation. It looks like an immune system that’s more active overall, with the anti-inflammatory response also ramping up in response. The researchers described this as altered immune regulation rather than straightforward neuroinflammation.
As with cortisol, the inflammatory cytokine profiles were not meaningfully altered by methylphenidate treatment. Four months of medication moved the behavioral needle without affecting the immune one.
Limitations
This is an open-label, quasi-experimental study with no placebo. The sample is small — 80 adolescents total, ~40 with ADHD — and several findings were significant in males only. Adolescent-specific findings may also not extrapolate directly to children or adults with ADHD.
That said, the associations held up through rigorous multivariable adjustment, and many of the findings are similar to older research on cortisol. We also need significantly more research on the inflammation markers with ADHD, as there isn’t much out there yet.
What to take away
Medication helps ADHD symptoms, but it appears to leave the underlying immune-hormonal profile largely untouched—at least in this sample.
Supporting ADHD-connected inflammation through nutrition and lifestyle might be the difference between you feeling unfocused or present. For 12 practical steps, read through this next article here.
If you want to go beyond symptom management and actually support your ADHD body at the biological level, my ADHD Nutrition Manual is where to start. You start by teaching your body to improve its cortisol responsiveness and connecting the pathways from your body to your brain. Then, you learn how to eat to best help your ADHD according to science – with practical resources to make it easy.
This article summarizes the research from the aforementioned studies and the author’s knowledge. It is for educational purposes only. Nothing in this article constitutes medical advice.
