With the expanded and extended use of stimulants comes mounting concern that the drugs might take a toll on the brain over the long run. Indeed, a smattering of recent studies, most of them involving animals, hint that stimulants could alter the structure and function of the brain in ways that may depress mood, boost anxiety and, contrary to their short-term effects, lead to cognitive deficits. Human studies already indicate the medications can adversely affect areas of the brain that govern growth in children, and some researchers worry that additional harms have yet to be unearthed.
Medicine for the Mind
To appreciate why stimulants could have negative effects over time, it helps to first understand what they do in the brain. One hallmark of ADHD is an underactive frontal cortex, a brain region that lies just behind the forehead and controls such “executive” functions as decision making, predicting future events, and suppressing emotions and urges. This area may, in some cases, be smaller than average in ADHD patients, compromising their executive abilities. Frontal cortex function depends greatly on a signaling chemical, or neurotransmitter, called dopamine, which is released in this structure by neurons that originate in deeper brain structures. Less dopamine in the prefrontal cortex is linked, for example, with cognitive difficulty in old age. Another set of dopamine-releasing neurons extends to the nucleus accumbens, a critical mediator of motivation, pleasure and reward whose function may also be impaired in ADHD.
Stimulants enhance communication in these dopamine-controlled brain circuits by binding to so-called dopamine transporters—the proteins on nerve endings that suck up excess dopamine—thereby deactivating them. As a result, dopamine accumulates outside the neurons, and the additional neurotransmitter is thought to improve the operation of neuronal circuits critical for motivation and impulse control.