This Research scientist Development Award has a short term goal to improve clinical trials methodology for pharmacotherapy of cocaine abuse and a long term goal to develop several neurobiologic methods to select more homogeneous groups of cocaine abusing opioid addicts for these pharmacotherapies. The first Specific Aim is to examine the combination of desipramine (DMI) with buprenorphine (BUP) in a randomized, placebo controlled clinical trial of 160 patients. A second Specific Aim under Dr. Rounsaville's mentoring is to examine two prognostic factors: depression and gender. These two Specific Aims are related to the Aim of my Career award to develop clinical trials methodology for the pharmacotherapy of diagnostically and prognostically homogeneous substance abusers, and they build on my clinical trials over the last five years with BUP and DMI. For my long term goal, I will work with Dr. Heninger and the Ribicoff Research faculty to become educated about and to develop, evaluate and apply neurobiologic tests (e.g. pharmacologic challenges, receptor and second messenger assessments, diagnostic imaging of brain neuroreceptors, new methods from molecular neurobiology) in order to identify more homogeneous patient groups. My career plans in clinical trials methodology under Dr. Feinstein include developing craving assessments, testing clinical strategies for analyzing quantitative urine toxicologies, and adapting cross-over and discontinuation research designs for drug dependence. The Yale Treatment Research Unit and Substance Abuse Research Center also have provided me with outstanding collaborators for clinical trials of mazindol, bupropion, and theophylline. Because of this strong and expanding group of mentors and collaborators, the proposed research program will be capable of maintaining the high productivity of its last five years.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA000112-07
Application #
3069467
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1987-09-01
Project End
1997-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Lukas, Scott E (2014) New perspectives on using brain imaging to study CNS stimulants. Neuropharmacology 87:104-14
Feingold, Alan; Oliveto, Alison; Schottenfeld, Richard et al. (2002) Utility of crossover designs in clinical trials: efficacy of desipramine vs. placebo in opioid-dependent cocaine abusers. Am J Addict 11:111-23
Winther, L C; Saleem, R; McCance-Katz, E F et al. (2000) Effects of lamotrigine on behavioral and cardiovascular responses to cocaine in human subjects. Am J Drug Alcohol Abuse 26:47-59
Farren, C K; Hameedi, F A; Rosen, M A et al. (2000) Significant interaction between clozapine and cocaine in cocaine addicts. Drug Alcohol Depend 59:153-63
Oliveto, A H; Feingold, A; Schottenfeld, R et al. (1999) Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. Arch Gen Psychiatry 56:812-20
Kosten, T R (1998) Pharmacotherapy of cerebral ischemia in cocaine dependence. Drug Alcohol Depend 49:133-44
McCance-Katz, E F; Kosten, T R; Jatlow, P (1998) Chronic disulfiram treatment effects on intranasal cocaine administration: initial results. Biol Psychiatry 43:540-3
Oliveto, A H; Farren, C; Kosten, T R (1998) Effect of LAAM dose on opiate use in opioid-dependent patients. A pilot study. Am J Addict 7:272-82
Kosten, T R; Cheeves, C; Palumbo, J et al. (1998) Regional cerebral blood flow during acute and chronic abstinence from combined cocaine-alcohol abuse. Drug Alcohol Depend 50:187-95
McCance-Katz, E F; Kosten, T R; Jatlow, P (1998) Concurrent use of cocaine and alcohol is more potent and potentially more toxic than use of either alone--a multiple-dose study. Biol Psychiatry 44:250-9

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