Methylphenidate (RITALIN), a piperidine derivative, is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Alarmingly, recent data from the Drug Enforcement Agency (DEA) indicate that methylphenidate (METH) abuse is widespread and represents a significant public-health concern. For example, between 1989 and 1993 emergency-room admissions involving METH increased by as much as 715%. There is accumulating evidence that the symptoms of childhood ADHD persist into adulthood in a significant number of cases, and adulthood ADHD is associated with high rates of psychiatric comorbidity, including cocaine (COC) abuse. Whether COC abusers with ADHD are at risk to abuse METH is unclear, and many clinicians are reluctant to prescribe stimulants to these patients because of their histories of COC abuse.
The specific aim of this project is to rigorously characterize the abuse potential of METH, the most commonly prescribed medication for the treatment of childhood and adulthood ADHD. To accomplish this aim, 3 inpatient, laboratory experiments will be conducted with volunteers with histories of COC abuse. Exp. 1 will replicate and extend findings from a previous study conducted in our laboratory that showed the discriminative-stimulus and subjective effects of METH are indistinguishable from those of COC. Exp. 2 will determine the relative reinforcing effects of METH and COC. Exp. 3 will determine the influence of rate of onset on the reinforcing, subjective and physiological effects of drugs by examining the effects of sustained- and immediate- release METH. We have two primary hypotheses. First, METH and COC will produce positive subjective effects and function as reinforcers. METH and COC will differ in terms of potency, but not efficacy. Second, sustained- release METH will have less abuse potential than immediate-release METH. The experiments proposed in the present application have at least 3 basic science and clinical implications. First these experiments will determine the abuse potential of METH in individuals with histories of COC abuse. Second, these experiments will determine whether decreasing the rate of onset of METH's effect reduces its abuse potential. Rate of onset is thought to be an important determinant of a drug's abuse potential. Third, these experiments may identify compounds that have reduced abuse potential (e.g., sustained-release METH) and may guide the pharmacological treatment of COC abusers with ADHD. The proposed experiments will also allow us to assess the effects of participating in non-treatment, inpatient, drug-abuse studies and to conduct retrospective analysis to determine the influence of individual differences (e.g., amount of cocaine use, amount and kind of other drug use, gender, ethnicity, socioeconomic status, as well as scores on a structured mental status exam, the Wender-Utah Rating Scale, the Beck Depression Inventory and several measures of personality function) on the behavioral and physiological responses to stimulants.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BBBP-1 (01))
Program Officer
Lynch, Minda
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kentucky
Schools of Medicine
United States
Zip Code
Reynolds, Anna R; Bolin, B Levi; Stoops, William W et al. (2013) Relationship between drug discrimination and ratings of subjective effects: implications for assessing and understanding the abuse potential of D-amphetamine in humans. Behav Pharmacol 24:523-32
Bolin, B Levi; Reynolds, Anna R; Stoops, William W et al. (2013) Relationship between oral D-amphetamine self-administration and ratings of subjective effects: do subjective-effects ratings correspond with a progressive-ratio measure of drug-taking behavior? Behav Pharmacol 24:533-42
Stanley, Matthew D; Poole, M├ęgan M; Stoops, William W et al. (2011) Amphetamine self-administration in light and moderate drinkers. Alcohol Clin Exp Res 35:443-53
Stoops, William W; Poole, Megan M; Vansickel, Andrea R et al. (2011) Methylphenidate increases choice of cigarettes over money. Nicotine Tob Res 13:29-33
Vansickel, Andrea R; Stoops, William W; Glaser, Paul E A et al. (2011) Methylphenidate increases cigarette smoking in participants with ADHD. Psychopharmacology (Berl) 218:381-90
Vansickel, Andrea R; Stoops, William W; Rush, Craig R (2010) Human sex differences in d-amphetamine self-administration. Addiction 105:727-31
Vansickel, Andrea R; Fillmorex, Mark T; Hays, Lon R et al. (2008) Effects of potential agonist-replacement therapies for stimulant dependence on inhibitory control in cocaine abusers. Am J Drug Alcohol Abuse 34:293-305
Vansickel, Andrea R; Stoops, William W; Glaser, Paul E A et al. (2007) A pharmacological analysis of stimulant-induced increases in smoking. Psychopharmacology (Berl) 193:305-13
Lile, Joshua A; Stoops, William W; Durell, Todd M et al. (2006) Discriminative-stimulus, self-reported, performance, and cardiovascular effects of atomoxetine in methylphenidate-trained humans. Exp Clin Psychopharmacol 14:136-47
Lile, Joshua A (2006) Pharmacological determinants of the reinforcing effects of psychostimulants: relation to agonist substitution treatment. Exp Clin Psychopharmacol 14:20-33

Showing the most recent 10 out of 17 publications