This application will be one of the first investigations to test a sequential treatment strategy in which a behavioral intervention will be augmented with a medication targeting dopamine release in order to boost treatment response among individuals not responding to the behavioral treatment alone. Further, analyses will be conducted to identify important cognitive and verbal processes associated with response to the behavioral intervention as well as the sequential treatment strategy. Psychosocial and Behavioral interventions are the cornerstone of addiction treatment. Our research group has demonstrated that deficient dopamine transmission, measured with the PET 11C-raclopride displacement paradigm, predicts poor response to a behavioral treatment program that included contingency management (CM). Other studies suggest that augmenting CM-based behavioral therapies with medications that boost mono-amine functioning can yield better outcomes than either treatment alone. These findings suggest that identifying individuals who do not respond to traditional behavioral therapies and enhancing these treatments with interventions tailored to boost dopamine transmission may be particularly effective for improving their overall efficacy. Among available medications, stimulants produce the most direct and potent augmentation of dopamine release and can significantly improve cognitive and behavioral functioning. A pilot study conducted by our group that included mixed amphetamine salts-extended release (MAS-ER) demonstrated that a regiment that included an agonist replacement strategy with stimulants maybe effective for promoting abstinence in severe cocaine dependent patients. Thus, we propose a Stage 2 treatment development trial in which 155 treatment- seeking cocaine dependent participants will receive a computer-assisted behavioral intervention based on the community reinforcement approach with contingency management (CRA + CM). Those who fail to achieve abstinence after the first 4 weeks will continue the behavioral treatment (CRA + CM) and be randomly assigned to a behavioral therapy enhancement strategy that will include either MAS-ER or placebo, over a 10- week double-blind trial. The Primary Aim is to test the hypothesis that among cocaine dependent patients who have failed to respond to an initial trial of behavioral therapy (CRA +CM), a greater proportion in the enhanced behavioral treatment arm CRA+CM/MAS-ER will achieve 3-weeks or more of continued abstinence compared to patients in the comparison group CRA+CM/PLACEBO. Secondary aims will characterize the cognitive and verbal processes associated with response to the computer-assisted behavioral treatment and test the combined treatment strategy on weekly cocaine use and craving, treatment retention, and quality of life. We will also explore potential moderators and mediators of treatment response across participants receiving the behavioral treatment alone and those receiving the combined treatment. These variables will include cognitive functioning, the use of relapse prevention skills, and changes in patient commitment language.
Cocaine Dependence is associated with substantial social, physical, and neurobiological problems that significantly impact the U.S. public health system. Psychosocial treatments can be helpful for many individuals. However, a significant proportion of individuals do not benefit from counseling alone, thus alternative treatment strategies are critically needed. Evidence suggests treatment failure is associated with neurobiological deficits. Thus, developing strategies that can significantly enhance the efficacy of behavioral interventions by targeting the neurobiological functioning of cocaine-dependent adults with medication has the potential to significantly impact the public health by addressing the needs of a sizeable treatment population.