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  • Title: The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.
    Author: Froeliger B, McConnell PA, Stankeviciute N, McClure EA, Kalivas PW, Gray KM.
    Journal: Drug Alcohol Depend; 2015 Nov 01; 156():234-242. PubMed ID: 26454838.
    Abstract:
    BACKGROUND: Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. METHODS: The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. RESULTS: As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]). CONCLUSIONS: Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.
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