Methylphenidate (MPH) is the most commonly prescribed medication for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The use and production of MPH have grown substantially in the past decade and so too have concerns over the drug's potential for abuse. Pre-clinical studies and human studies with healthy volunteers suggest that the abuse potential of MPH is comparable to other commonly abused stimulants, such as d-amphetamine and cocaine. There is also concern as to whether clinical use of MPH is associated with substance abuse in individuals with ADHD. To date, however, no studies have examined the abuse potential of MPH in the population to whom it is most frequently prescribed. The primary goal of the proposed research is to rigorously characterize the behavioral pharmacological profile of MPH in a sample of adults with ADHD compared to a sample of healthy adults. To accomplish this goal, two experiments are proposed over the three-year funding period for this application. The first experiment will assess the discriminative stimulus and subjective effects of methylphenidate in samples of adults with and without ADHD. It is hypothesized that, compared to the non-diagnosed control group, the individuals with ADHD will be less accurate in discriminating methylphenidate from placebo and will report subjective effects that are lower in magnitude. The second experiment will assess the reinforcing effects of methylphenidate in a group of individuals with ADHD versus a non-diagnosed group. It is hypothesized that the reinforcing effects of MPH will be lower in the group diagnosed with ADHD. This research is important for at least three reasons. First, it will address a significant public health concern by explicitly evaluating whether MPH, in its typical formulation, possesses significant abuse liability in individuals with ADHD who are likely to receive the drug for clinical purposes. Second, the proposed research will systematically investigate the behavioral pharmacological profile of MPH in healthy, control participants thus extending the limited previous work on the potential for the drug's misuse in non-clinical populations. Third, the proposed research will extend understanding about the neuropharmacological mechanisms underlying the clinical effects of this drug and potential differences in these mechanisms across the two groups. This will be accomplished by directly comparing the behavioral pharmacological profile of MPH in individuals with ADHD and control subjects and by examining these effects in relation to the pharmacokinetic profile of the drug in both groups. [unreadable] [unreadable]
NIH ExPorter
NIH ExPorter