Functional Magnetic Resonance Imaging of N-acetylcysteine in 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

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

Exclusion criteria

• Do not meet DSM-IV criteria for cocaine-use disorder.
• 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.
• Meet DSM-IV criteria for current alcohol or other substance-use disorder dependence (with the exceptions of nicotine, cocaine and opioids).
• Have previously taken or currently take NAC.
• Have asthma (due to possible complications with NAC).
• Cannot commit to 4-weeks of study participation or are unwilling to accept randomization.
• Have any contraindications for MRI scanning (e.g., pregnancy, color-blindness, claustrophobia, metal implants that could interfere with MRI, any other contraindication to scanning).
• 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.
• 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.
• Are not fluent in English.
• Do not have at least a 6th grade reading level.
• Cannot provide written, informed consent.