The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study

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 2400 mg N -Acetylcysteine (1200 mg 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  p 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.