Three projects related to the treatment of intravenous drug abusers are included in this five year proposal; 1), pharmacotherapy for IV cocaine and opioid abuse, (inpatient (IP) n=100; outpatient (OP) n=440) 2. relapse prevention for pregnant cocaine abusers(n=60, 3. pharmacotherapy of HIV related cognitive impairment (IP n=50). These studies will occur within a 6 bed inpatient unit (1 month protocols) and 59 slot outpatient methadone and buprenorphine program (6 month protocols). Project 1 will examine dopamine agonists (amantadine, bromocriptine, mazindol) and antagonists (flupenthixol) and serotonergic augmentation of treatment (sertraline), as well as buprenorphine alone and in combination with these agents to treat cocaine abusing opioid addicts. Outpatient randomized clinical trials will use these medications within methadone or buprenorphine maintenance and include 6 month discontinuation studies (using 3 month placebo substitution at month 3 in half the group) to assess optimum duration of treatment. Neurobiological assessments including SPECT imaging of dopamine receptors, L-dopa and tryptophan challenges will be used to develop new medications for cocaine abuse treatment. Assessment of craving response to cocaine cue exposure will also provide information about treatment effects. Project 2 will use 3 weeks of intensive relapse prevention therapy to compare inpatient to 5 days per week outpatient treatment for 8 weeks will follow and outcome will be assessed at 6 months. Project 3 will compare pharmacotherapy with AZT, peptide T and/or cholinergic agents for HIV related cognitive impairment. Four week inpatient randomized clinical trials of detoxified opioid addicts and patients on methadone maintenance will be conducted. Outcome will focus on neuropsychological testing and SPECT blood flow scans. Overall, the Treatment Research Unit will provide innovative services to over 700 drug abusers at high risk for AIDS and its complications.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Demonstration and Dissemination Projects (R18)
Project #
5R18DA006190-02
Application #
3441731
Study Section
Special Emphasis Panel (SRCD (01))
Project Start
1989-09-30
Project End
1994-08-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
2
Fiscal Year
1991
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
Oliveto, A H; Rosen, M I; Kosten, T A et al. (1998) Hydromorphone-naloxone combinations in opioid-dependent humans under a naloxone novel-response discrimination procedure. Exp Clin Psychopharmacol 6:169-78
Kosten, T R (1998) Pharmacotherapy of cerebral ischemia in cocaine dependence. Drug Alcohol Depend 49:133-44
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
Schottenfeld, R S; Pakes, J R; Kosten, T R (1998) Prognostic factors in Buprenorphine- versus methadone-maintained patients. J Nerv Ment Dis 186:35-43
van Dyck, C H; McMahon, T J; Rosen, M I et al. (1997) Sustained-release methylphenidate for cognitive impairment in HIV-1-infected drug abusers: a pilot study. J Neuropsychiatry Clin Neurosci 9:29-36
Hameedi, F A; Woods, S W; Rosen, M I et al. (1997) Dose dependent effects of yohimbine on methadone maintained patients. Am J Drug Alcohol Abuse 23:327-33
Schottenfeld, R S; Pakes, J R; Oliveto, A et al. (1997) Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Arch Gen Psychiatry 54:713-20
Mayes, L C; Carroll, K M (1996) Neonatal withdrawal syndrome in infants exposed to cocaine and methadone. Subst Use Misuse 31:241-53
Wallace, E A; Wisniewski, G; Zubal, G et al. (1996) Acute cocaine effects on absolute cerebral blood flow. Psychopharmacology (Berl) 128:17-20
Kosten, T R; Malison, R; Wallace, E (1996) Neuropsychological abnormalities in cocaine abusers: possible correlates in SPECT neuroimaging. NIDA Res Monogr 163:175-92

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