Project 6D: Risky Decision Making in Methamphetamine Users: The Role of Opioid Blockade

Todd Korthuis, M.D., Principal Investigator

The primary goal of this MARC pilot proposal is to probe the neural mechanism of the effect of endogenous opioid blockade on impulsive choice in HIV-infected methamphetamine (MA) users. The proposal extends the scope of a recently funded NIDA award (R21DA033182) assessing neural mechanisms of endogenous opioid blockade on impulsive choice in non-HIV-infected MA users, to include HIV-infected subjects. The parent study is a randomized, placebo-controlled study of the effect of extended-release naltrexone (XR-NTX) on delay discounting and its neural substrate in 40 non-HIV-infected subjects. In the pilot study, 12 recently abstinent, HIV-infected MA users recruited from HIV clinics and addiction treatment centers in Portland, Oregon will be assessed with fMRI and delay discounting task at baseline and 28-days following XR-NTX vs. placebo injection.

In Aim 1, we determine the neural basis of impulsive choice in HIV-infected MA users. We hypothesize that activity (a) in ventral striatum (VS) and ventrolateral prefrontal cortex (VLPFC) will scale with magnitude of reward, (b) in anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) with length of delay and (c) in anterior insula and the inferior parietal lobule (IPL) with the process of making a decision. In Aim 2, we assess the effect of endogenous opioid blockade on impulsivity and its neural substrate.

We hypothesize that subjects randomized to NTX will show decreased impulsivity (preference for immediate rewards) from baseline compared to those randomized to placebo (hypothesis 2.1), and that subjects with the greatest decrements in impulsivity will exhibit decreased cerebral response to reward magnitude in VS and VLPFC and decreased response to length of delay in ACC and DLPFC. These effects will be more pronounced in the NTX group (hypothesis 2.2). The proposed work will provide the first evidence for the effect of endogenous opioid blockade on risky decision-making and provide crucial preliminary data for an R01 study in HIV-infected MA users. Such treatments have the potential to advance the National HIV/AIDS Strategy goal of reducing HIV transmission.