This project proposes to use an efficient human laboratory screening methodology to examine the effects of various pharmacological treatments that may modulate the effects of cocaine relevant to its abuse.
The aim i s to contribute to the identification and development of medications that may be useful in the treatment of cocaine abuse. This is an ongoing and productive project, and this is an application for its continuation. The efficient human laboratory screening methodology proposed is one that has been developed during the first years of this project's operation. A methodological refinement to be added during this renewal period is the assessment of pharmacological effects on elicitation of cocaine-related conditioned craving. Pharmacological effects on cocaine's direct effects and on cocaine-elicited craving for cocaine will continue to be assessed. In addition, effects of the pharmacological pretreatments that may be relevant to their safety and/or acceptability will be assessed. Assessment of both cocaine effects and pharmacological pretreatment effects is multi-dimensional, including subjective, behavioral, and physiological effects. The primary general method to be used in these studies is that of double-blind, controlled human laboratory cocaine challenges under various conditions of pharmacological pretreatment. To maximize the practical efficiency of these studies, each cocaine challenge session will involve multiple injections and will produce a cocaine dose-effect function, and the pharmacological pretreatments will be provided on a chronic basis with the dose progressively increasing across days, so that relatively high doses can be assessed and so that effects of chronic treatment can be assessed. While the specific pretreatment drugs most appropriate for testing will be continually reassessed during the course of the project, those judged most promising, appropriate, and/or informative and, therefore, planned at the present time include: naltrexone, cocaine itself (orally), carbamezepine, flupenthixol, bromocriptine, bupropion, fluoxetine, haloperidol, desipramine, ondansetron. These studies are relevant to the treatment of intravenous drug abuse and to efforts to reduce the spread of AIDS and HIV infection by reducing HIV-associated risk behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA005196-08
Application #
2117504
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1987-09-30
Project End
1997-07-31
Budget Start
1994-09-01
Budget End
1995-07-31
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Donny, Eric C; Bigelow, George E; Walsh, Sharon L (2006) Comparing the physiological and subjective effects of self-administered vs yoked cocaine in humans. Psychopharmacology (Berl) 186:544-52
Houtsmuller, Elisabeth J; Notes, Lisa D; Newton, Thomas et al. (2004) Transdermal selegiline and intravenous cocaine: safety and interactions. Psychopharmacology (Berl) 172:31-40
Donny, Eric C; Bigelow, George E; Walsh, Sharon L (2004) Assessing the initiation of cocaine self-administration in humans during abstinence: effects of dose, alternative reinforcement, and priming. Psychopharmacology (Berl) 172:316-23
Donny, Eric C; Bigelow, George E; Walsh, Sharon L (2003) Choosing to take cocaine in the human laboratory: effects of cocaine dose, inter-choice interval, and magnitude of alternative reinforcement. Drug Alcohol Depend 69:289-301
Lin, S N; Moody, D E; Bigelow, G E et al. (2001) A validated liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method for quantitation of cocaine and benzoylecgonine in human plasma. J Anal Toxicol 25:497-503
Nann-Vernotica, E; Donny, E C; Bigelow, G E et al. (2001) Repeated administration of the D1/5 antagonist ecopipam fails to attenuate the subjective effects of cocaine. Psychopharmacology (Berl) 155:338-47
Spanbauer, A C; Moody, D E; Foltz, R L et al. (2000) A gas chromatographic-positive ion chemical ionization-mass spectrometric method for determination of cocaine, benzoylecgonine, ecgonine methyl ester, and norcocaine in plasma: detection of norcocaine in plasma after oral administration of cocaine. J Anal Toxicol 24:453-5
Walsh, S L; Haberny, K A; Bigelow, G E (2000) Modulation of intravenous cocaine effects by chronic oral cocaine in humans. Psychopharmacology (Berl) 150:361-73
Stitzer, M L; Walsh, S L (1997) Psychostimulant abuse: the case for combined behavioral and pharmacological treatments. Pharmacol Biochem Behav 57:457-70
Preston, K L; Sullivan, J T; Strain, E C et al. (1996) Enhancement of cocaine's abuse liability in methadone maintenance patients. Psychopharmacology (Berl) 123:15-25

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