The objective of this research is to identify the functional neural mechanisms (as assessed using fMRI) of short-term N-acetylcysteine (NAC) administration among methadone-maintained individuals with cocaine dependence.

The objective of this research is to identify the functional neural mechanisms (as assessed using fMRI) of short-term N-acetylcysteine (NAC) administration among methadone-maintained individuals with cocaine dependence. Specifically, this application proposes to conduct a randomized, double-blind, placebo-controlled, cross-over pilot study to examine the effects of 7-day NAC administration (2400mg/day) on the neural networks engaged during response inhibition (Go/No-Go task) and affective (emotion-regulation task) processes among cocaine-dependent, methadone-maintained individuals (n=40; 20 per treatment-order condition).

Inclusion Criteria:

1. enrollment in the APT methadone program and maintained on a stable dose of methadone for ≥ 2 weeks
2. males or females, aged 18-65
3. confirmed DSM-IV diagnosis of current cocaine use disorder as assessed at the screening assessment
4. for women of a child-bearing age, acceptable birth control method
5. ability to commit to 4 weeks of study participation plus 1-month follow-up
6. willingness to be randomized to NAC or placebo
7. eligibility for MRI scanning and willingness to participate in MRI scanning.

Exclusion Criteria:

1. Do not meet DSM-IV criteria for cocaine-use disorder.
2. Meet DSM-IV psychiatric classifications for lifetime schizophrenia or bipolar disorder, or exhibit significant current suicidal or homicidal plans and intent such that hospitalization is required.
3. Meet DSM-IV criteria for current alcohol or other substance-use disorder dependence (with the exceptions of nicotine, cocaine and opioids).
4. Have previously taken or currently take NAC.
5. Have asthma (due to possible complications with NAC).
6. Cannot commit to 4-weeks of study participation or are unwilling to accept randomization.
7. Have any contraindications for MRI scanning (e.g., pregnancy, color-blindness, claustrophobia, metal implants that could interfere with MRI, any other contraindication to scanning).
8. Have lab work (complete blood count, urinalysis, liver function tests, thyroid function tests) suggesting the presence of any abnormalities or have a significant or unstable medical illness.
9. Are women who are pregnant or of a child-bearing age who do not agree to adequate contraception to prevent pregnancy during the study period.
10. Are not fluent in English.
11. Do not have at least a 6th grade reading level.
12. Cannot provide written, informed consent.