This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Twenty participants will complete procedures during treatment with placebo, NAC 1800mg, and NAC 3600mg, using within-subject, double-blind, placebo-controlled design. After 2 days of treatment with study medication, cue-induced craving will be assessed using visual analogue rating scales prior to and after exposing participants to MA and neutral cues using our newly developed virtual reality (VR) apparatus. Participants will then complete sessions in which they receive a non-contingent dose of 10mg smoked MA (equivalent to 5mg IV MA) or placebo followed by 5 choices between receiving identical doses or receiving nothing. One session will be conducted at 10am and the other at 1pm. The order of availability of MA and placebo will be counterbalanced within each participant. They will smoke the MA, and given the bioavailability of smoked MA is about 50% (Harris and colleagues reported absolute bioavailability of 37.4 14.2% (Harris, Boxenbaum et al. 2003)) we will load the pipe 10mg MA to approximate the effects of 5mg IV MA. Any alterations in the reinforcing effects of MA associated with NAC treatment will be evident as changes in the number of choices made for MA. After discontinuation of study medication participants will be discharged.
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