Name of Project: An Assessment of the Interaction
of Cocaine with Amantadine and Baclofen, Alone and in Combination:
Cardiovascular Responses, Subjective Responses, Reinforcing Efficacy,
and Cue Reactivity
Principal Investigator: Thomas Newton, M.D.
Co-Principal Investigator: Steven Shoptaw, Ph.D.
Project Director: Nicolette van Sluis, M.A.
Funding Agency: National Institute on Drug Abuse
(NIDA)
Funding Period: September 1999-August 2004
Scope of Project: This is a human clinical pharmacology
study to assess potential interactions between cocaine and combined
amantadine and baclofen treatment. The main purpose of this study
is to assess the safety of combined amantadine and baclofen treatment
while experienced volunteer cocaine-dependent users (N = up to
8
completers) undergo experimental intravenous cocaine challenges
(0, 20, or 40 mg). In doing this, valuable information is gained
concerning any possible interactions between such treatment and
cocaine use
prior to a NIDA clinical trial involving these medications. Craving
for drugs is a critical component of addictive disorders, with
the existing premise that neuroadaptations in the mesolimbic dopamine
(DA)
system are imperative in drug use and relapse. Therefore, the
second purpose of this study is to assess the ability of combined
amantadine and baclofen pretreatment to alter the reinforcing
efficacy, ameliorate
the euphorogenic properties, and diminish cue-induced craving
for cocaine. A reduced startle amplitude and enhanced prepulse
inhibition (PPI) in abstinent cocaine users has been reported
and attributed to a state of decreased DA activity in this population.
The third purpose of this study, therefore, will be to examine
the effects of cocaine on startle amplitude and PPI during cocaine
challenges prior to and subsequent to a pretreatment combination
with amantadine and baclofen. Pharmacokinetics parameters for
cocaine and study medications also will be assessed.
For more information, contact Thomas
Newton.
Last updated - 07/29/2003
Last reviewed - 07/28/3003