Our promising research in healthy human volunteers has provided preliminary evidence that isradipine, a dihydropyridine-class calcium channel antagonist (DCCCA), significantly reduces the rewarding (including euphoric) effects of methamphetamine mediating its abuse potential. This proposal aims to determine if these anti-rewarding effects of isradipine will generalize to methamphetamine dependent individuals during drug-taking, thereby laying the foundation for the programmatic development of DCCCA in future clinical trials as treatment agents for methamphetamine dependence. Using state-of-the-art measures of human liability assessment, we plan to conduct two placebo-controlled, double-blind studies using a counter-balanced (for sequence and ordinal position) cross-over design in which we will examine the behavioral and physiological effects of d-methamphetamine both alone and in combination with isradipine. Subjects will be forty-two non treatment-seeking methamphetamine dependent men and women. Experiment #1, a proof-of-concept analysis, will test the hypothesis that acute isradipine pretreatment reduces methamphetamine-induced changes in subjective mood and other measures of human abuse liability. Secondarily, we will determine, if and by how much, d-methamphetamine-induced changes in cognitive, psychomotor, and physiological function, are altered by isradipine in non-fatigued subjects during drug-taking. Experiment #2 addresses issues of potential clinical effectiveness and utility by testing the hypothesis that repeated isradipine administration will: a) antagonize d-methamphetamine's rewarding effects, and b) prove to be clinically tolerable by decreasing d-methamphetamine's pressor effects while producing no cognitive or psychomotor deterioration. Establishing isradipine's effectiveness and tolerability in the human laboratory lays a solid foundation for its use in future clinical trials for the treatment of methamphetamine dependence. This study supports NIDA's mission to develop effective medications for the treatment of methamphetamine dependence, and to understand the pharmaco-behavioral processes associated with psychostimulant use.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA012969-01A1
Application #
6197383
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Oversby, Steven
Project Start
2000-09-30
Project End
2004-05-31
Budget Start
2000-09-30
Budget End
2001-05-31
Support Year
1
Fiscal Year
2000
Total Cost
$293,066
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Johnson, Bankole A; Messing, Robert O; Charness, Michael E et al. (2011) Should the reorganization of addiction-related research across all the National Institutes of Health be structural?--The devil is truly in the details. Alcohol Clin Exp Res 35:572-80
Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima et al. (2007) Effects of topiramate on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition in recently abstinent methamphetamine-dependent individuals. Prog Neuropsychopharmacol Biol Psychiatry 31:123-30
Johnson, Bankole A; Wells, Lynda T; Roache, John D et al. (2007) Kinetic and cardiovascular effects of acute topiramate dosing among non-treatment-seeking, methamphetamine-dependent individuals. Prog Neuropsychopharmacol Biol Psychiatry 31:455-61
Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima et al. (2007) Effects of acute topiramate dosing on methamphetamine-induced subjective mood. Int J Neuropsychopharmacol 10:85-98
Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima et al. (2005) Effects of isradipine on cocaine-induced changes in cognitive performance in recently abstinent cocaine-dependent individuals. Int J Neuropsychopharmacol 8:549-56
Roache, John D; Johnson, Bankole A; Ait-Daoud, Nassima et al. (2005) Effects of repeated-dose isradipine on the abuse liability of cocaine. Exp Clin Psychopharmacol 13:319-26
Johnson, Bankole A; Wells, Lynda T; Roache, John D et al. (2005) Isradipine decreases the hemodynamic response of cocaine and methamphetamine results from two human laboratory studies: results from two human laboratory studies. Am J Hypertens 18:813-22
Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima et al. (2005) Effects of isradipine on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition. Psychopharmacology (Berl) 178:296-302
Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima et al. (2005) Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects. Int J Neuropsychopharmacol 8:203-13