This phase two, single-site study will utilize a double-blind, placebo-controlled, randomized, pre-/post-treatment design to investigate the effect of NAC dosing on brain GSH levels and measure temporally concordant plasma levels of several established circulating markers of oxidative stress. Three study groups, of 20 subjects each (for a total of 60 who completed all components of the study), will each be administered a different dose (0 mg/day, 900mg/day, 3600mg/day) of the study intervention over a four week period; N-acetylcysteine (NAC) treatment. Subjects receiving 0 mg/day dose will be administered a placebo. Baseline visit assessments will include blood collection, survey questionnaires, MRI and MRS imaging. Subjects whose initial screening confirms low GSH level at baseline will be provided with a 4-week supplement of anonymized NAC or placebo caplets. After 4 weeks, subjects will then undergo a follow-up visit to repeat the baseline assessments.
Inclusion Criteria: - Males or females, ages 21 to 60 years (inclusive). - Baseline GSH levels at or less than a predefined cutoff value. - Primary diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). - Willing and capable of providing informed consent. Exclusion Criteria: - Significant and/or comorbid axis I (especially mood and anxiety) and axis II disorders. - Any significant neurological illness or impairment. - Other unstable medical conditions (asthma, hypertension, endocrine or metabolic disease, etc). - History alcohol abuse. - Positive urine toxicology at screening and on days of assessments. - Positive pregnancy test at screening or on days of assessments. - Contra-indication for clinical MRI scan (e.g., pacemaker, metallic prosthesis). - Baseline GSH levels higher than a predefined cutoff value.