There is growing consensus that optimizing treatment outcomes for substance use disorders may beachieved through careful integration of pharmacologic and psychosocial interventions. Working closely withProject 3 for the identification of compounds, the proposed project will assess the ability of selectpharmacotherapeutic agents to augment the therapeutic effects of a cue exposure intervention formethamphetamine (METH) dependence and to preliminarily assess impact on measures of cognitivefunctioning. D-cycloserine (DCS), a partial glutamate agonist facilitates associative learning, is one agentlikely to be explored and has been chosen as the prototype for this application.
The specific aims are: 1. To develop a set of environmental cues specific to METH use; 2. To investigatethe ability of the METH-specific cues to elicit craving and physiological reactivity in METH-dependentindividuals; 3. To explore the impact of DCS on response to METH-related cues; and 4. To preliminarilyexplore the relationship of cognitive function to DCS response in METH dependent individuals.We will initially develop methamphetamine cues through conducting interviews with METH dependentindividuals and pilot testing to assess the ability of the cues developed to provoke craving and physiologicresponse. In vivo, picture and video cues will be developed within the first six months. In parallel, a VirtualReality METH cue environment will be developed to be used in future studies. After a satisfactory set of cueshas been developed, METH-dependent individuals will be recruited to receive either DCS or a placebo priorto each of two, one-hour exposure sessions in which drug use and other drug-related stimuli will bepresented using in vivo and video cue presentation. Multiple assessments of craving and physiologicreactivity will be obtained during and after the cue exposure sessions and during an unmedicated testsession one-month after the second cue exposure session. The primary outcome measures will besubjective (craving, desire to use) and physiologic (heart rate, skin conductance) responses to METH cues.In summary, this pilot project will begin with the development of METH-related environmental cues to beused both in this project and Project 2. Guided by the findings of Project 3, the use of innovativepharmacologic approaches to the treatment of METH dependence through the facilitation of extinction ofresponses to METH conditioned cues will be explored. The impact of pharmacologic agents on cognitivefunction in METH dependent individuals will also be preliminarily explored. Through working closely with theother center studies, methodology will be developed and pilot data generated to guide a P50 application.
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