Long-term use of stimulants for attention-deficit/hyperactivity disorder (ADHD) does not appear to cause lasting changes in brain development, according to a study published in . Advances in neuropsychopharmacology and biological psychiatry.
Medications such as methylphenidate, commonly known as Ritalin, are widely prescribed to treat ADHD. This condition is characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. Stimulants work by increasing levels of brain chemicals, particularly dopamine and noradrenaline, which help regulate attention and behavior.
Although these drugs are considered highly effective in the short term, scientists have long debated whether taking these drugs during childhood, when the brain is still developing, can cause permanent biological changes. Animal studies suggest that exposure during sensitive developmental periods may alter the way the brain’s dopamine system matures, raising questions about possible long-term effects.
Dutch researchers led by Zahler van der Pal of the University of Amsterdam followed participants who had previously taken part in a randomized controlled trial for 16 weeks for four years.
The first trial included boys and adult men with ADHD who were given either methylphenidate or a placebo for four months. Previous studies have demonstrated changes in the brain’s response to drugs in children, but not adults, even after treatment has stopped.
The new study followed 56 men with ADHD. The participants included 32 adolescents with an average age of 11 years at the start of the original study and 24 adults with an average age of 30 years. Over the next four years, some participants continued to take stimulants in their daily practice, while others did not.
Both at the beginning of the study and four years later, participants underwent brain scans (pharmacological magnetic resonance imaging) before and after a single dose of methylphenidate. The researchers measured blood flow in specific brain regions involved in attention and decision-making, including the anterior cingulate cortex, medial prefrontal cortex, striatum, and thalamus. Changes in blood flow serve as indirect markers of how active certain brain systems are.
The main findings were encouraging. Researchers found no evidence that long-term stimulant use causes permanent age-specific changes in brain development. The short-term differences seen in children during the first trial were still undetectable 4 years later.
“The previously identified short-term effects may be due to neuroplasticity, the brain’s ability to adapt and reorganize in response to internal and external stimuli,” the research team hypothesized.
However, the researchers identified some age-related patterns. In adults, those who took more stimulants over a four-year period tended to have lower resting blood flow in a deep brain region called the thalamus. In adolescents, higher drug exposure was associated with smaller brain responses in the medial prefrontal cortex when methylphenidate was administered.
Importantly, these patterns were already present at the start of the study, before treatment began, suggesting they may reflect pre-existing brain differences rather than drug effects. The researchers also found that, only during adolescence, the brain’s response patterns matched the distribution of a particular type of dopamine receptor, known as the D1 receptor.
Importantly, none of the brain measurements were directly related to the severity of a person’s ADHD symptoms. This further suggests that the observed brain differences do not directly explain symptom levels.
Research has limitations. The sample size was modest, some participants dropped out over time, and drug use during follow-up was not tightly controlled. Also, because only men were included, the findings may not apply to women.
The study, “Association between long-term stimulant treatment and functional brain response to methylphenidate in adolescents and adults with attention-deficit/hyperactivity disorder,” was authored by Zarah van der Pal, Liesbeth Reneman, Henk JMM Mutsaerts, Antonia Kaiser, Marco A. Bottelier, Hilde M. Geurts, and Anouk Schrantee.
