This project will examine in human cocaine users the interactions of cocaine with drugs currently used or proposed for use in the treatment of cocaine abuse. In addition, the project will examine the effects of cocaine in methadone maintenance patients, a population at high risk for cocaine abuse. The project aims to identify potentially beneficial (e.g., efficacy in blockade of cocaine effects) and potentially harmful (e.g., changes in cardiovascular function or increases in cocaine-induced euphoria) effects produced when cocaine is self-administered during treatment with pharmacological agents. In a residential human experimental laboratory the physiological, subjective, and behavioral effects of cocaine challenge alone and in combination with a test drug will be intensively studied under controlled double-blind conditions. In the first study the effects of cocaine alone will be compared in methadone-dependent cocaine abusers and in non-opioid using cocaine abusers. Studies to examine the effect of repeated administration of two antidepressants, desipramine and trazodone, on response to cocaine challenge will then be conducted in methadone maintenance patients who abuse cocaine. A second group of studies will examine the interaction between cocaine and drugs proposed for use in cocaine abuse treatment (haloperidol, bromocriptine, amantadine, and 1-dopa) in non-opioid dependent cocaine abusers. These experiments will provide multifaceted data concerning the safety and efficacy of various pharmacological agents in a population at high risk for self-administration of cocaine and may provide information on which to base decisions about the treatment of cocaine abusers.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA005196-01
Application #
3211369
Study Section
(SRCD)
Project Start
1987-09-30
Project End
1992-08-31
Budget Start
1987-09-30
Budget End
1988-08-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
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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