Attention deficit hyperactivity disorder (ADHD) is a common and disabling neutopsychiatric disorder that afflicts 3-7% of children and 1-5% of adults. Stimulant drugs are the mainstay of treatment for ADHD. Of the various stimulant drugs used to treat ADHD, amphetamine is among the most often prescribed, both to children and adults. A significant body of data indicates that amphetamine has the potential to destroy brain dopamine (DA) axons and axon terminals in animals. The possibility that humans receiving amphetamine for the treatment of ADHD might incur similar amphetamine-induced DA ncurotoxicity has not been investigated, largely because the doses that produce DA neurotoxic effects in animals are higher, on a ing/kg basis, than the doses used in the treatment of ADHD. However, recent preliminary findings in our laboratory indicate that baboons treated with an oral dosing regimen of amphetamine similar to that used commonly to treat ADHD sustain DA neurotoxic changes in the striatum. Pilot data also indicate that plasma levels of .amphetamine associated with brain DA ncurotoxicity in baboons are on the order of those reported in humans treated with amphetamine for ADHD.
The aims of the proposed studies are: 1) To confirm our preliminary observations in a larger number of adult baboons, and to see if they can be extended to adolescent animals; 2) To determine if findings in baboons can be extended to another non-human primate species (squirrel monkeys, adult and adolescent) known to metabolize amphetamine in a manner similar to humans ; and 3) To measure plasma concentrations of amphetamine engendered by dosing regimens of amphetamine in non-human primates, in order to compare the levels and pharmacokinctic profiles of amphetamine associated with DA ncurotoxicity in 2 non-human primate species with those previously documented in humans. Together, results of the proposed studies will help determine whether concern over possible amphetamineinduced DA neurotoxicity in humans receiving amphetamine for the treatment of ADHD is warranted, and if controlled studies of possible amphetamine-induced DA neurotoxicity in human ADHD cohorts are indicated.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Mattison, Donald R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Slezak, Jonathan M; Mueller, Melanie; Ricaurte, George A et al. (2018) Pharmacokinetic and pharmacodynamic analysis of d-amphetamine in an attention task in rodents. Behav Pharmacol 29:551-556
Ricaurte, George A; Mechan, Annis O; Yuan, Jie et al. (2005) Amphetamine treatment similar to that used in the treatment of adult attention-deficit/hyperactivity disorder damages dopaminergic nerve endings in the striatum of adult nonhuman primates. J Pharmacol Exp Ther 315:91-8