21/03/2026
Neurons communicate via neurotransmitters both classical (dopamine, serotonin, acetylcholine, glutamate, GABA, etc.) or peptides (norepinephrine, epinephrine, substance P, etc.) released at the synaptic cleft or neuro-hormonally. Reduced levels of dopamine (DA) and norepinephrine (NE) have historically been hypothesized to be a major cause of ADHD. Evidence supporting this hypothesis stems from the fact that psychostimulants, which are the first-line treatment for ADHD, increase levels of DA and NE, and as such are deemed effective treatment of ADHD symptoms. These ADHD medications are classified as either stimulants, which include amphetamine (AMPH), or methylphenidate (MPH)-based pharmacotherapies, or non-stimulants (i.e., atomoxetine (ATX)) which do not directly increase DA release. Stimulant medications have common side effects, including decreased appetite, insomnia, irritability, and increased blood pressure resulting from DA and NE release. However, stimulant medications like Adderall and Ritalin are often abused as cognitive enhancers in academic settings. Additionally, the long-term effects of these medications on cognitive processes are not fully determined, and their long-term effects on the fetal brain during pregnancy are also not fully understood. Here, we review the monoamine networks thought to be involved in the symptoms presented in ADHD.
Both stimulant and non-stimulant ADHD medications modulate the levels of monoamines that are available within the brain. This includes DA, NE, and serotonin (5-HT), which all form distinct pathways in the central nervous system (CNS). Monoamines have a fundamental role in modulating mood, cognition, and behavior, and perturbations in their transmission have been implicated in ADHD and the above-mentioned symptoms. Despite the historical focus on these transmitters in ADHD pathophysiology, the variation in ADHD phenotypes alongside case-by-case differences in brain region-specific transmitters has made it difficult to deduce whether it is a reduction or an augmentation of monoaminergic transmission in the brain that causes ADHD symptoms.
Reference: Yacoub, M. (2025)
