Stimulant medications (methylphenidate (MPH) and amphetamine (AMP)) have been used for the treatment of ADHD for >50 years. At the time of their approval, the regulatory processes were much less stringent with respect to safety information than those of today. Currently, around 4 million children are treated with stimulants each day in the USA (Zuvekas and Vitiello, 2012), which has led to valid concerns over their possible developmental effects, particularly as children and adolescents are being treated with stimulant medications at the time of profound neural, hormonal, and physical changes and usually over relatively long time periods—several years. A chief concern has been the potential adverse effects of stimulant medications to the developing brain, specifically as they relate to dopamine (DA) brain function and the risk for substance use disorder (Volkow and Swanson, 2008). This is because stimulant medications increase DA in the nucleus accumbens, which is the pharmacological effect that underlies drug reward and that with repeated use triggers the neuroadaptations in dopaminergic and glutamatergic signaling associated with addiction (Kalivas and Volkow, 2005). Indeed, MPH and AMP are abused and can result in addiction (Volkow and Swanson, 2003). Another clinical concern has been the potential adverse effects of stimulant medications on physical growth (Swanson et al, 2007). However, resolution of these critical clinical issues about stimulant medications has been difficult to address directly in humans because of ethical and practical considerations.

Preclinical studies have aimed to resolve this issue, and over the past 10 years several studies have assessed the effects of chronic exposure to stimulants during early development (corresponding to childhood and adolescence) in the sensitivity to drug rewards and to its effects on brain DA signaling. The findings have been inconclusive, with some studies showing enhanced sensitivity to drug rewards and changes in DA signaling whereas others reporting no changes or decreased drug responses (Volkow and Insel, 2003). The reasons for discrepancies are many, and include among others the time at which medications are initiated as well as the doses and route of administration used (Volkow and Insel, 2003). On the other hand, there have been no reported preclinical studies on the effects of stimulant medications on physical growth.

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