This research study evaluates the effects of anFDA-approved medication NAC in individuals with Bipolar Disorder. Participants in the study will will be assigned to two medication conditions and will take both NAC and a matched placebo. The order in which they take each medication will be random. Study medication will be taken for 14 days. There will be 5 study visits, with 2 MRI brain imaging scans completed. Questionnaires and clinical interview measures will be completed at study visits along with consistent assessment of potential side effects from study medication.

Inclusion Criteria:

1. Ages 18-60 years
2. Meet DSM-5 criteria for bipolar I or II disorder
3. Able to provide informed consent and read, understand, and accurately complete assessment instruments
4. Willing to commit to medication treatment and follow-up assessments
5. Meets DSM-5 criteria for any mood episode (i.e., Major Depressive, Hypomanic, Manic), Current or In Partial Remission
6. Prescribed daily use of at least one FDA-approved mood stabilizing medication (i.e., lithium, divalproex sodium, lamotrigine, 2nd generation antipsychotic)
7. Willing to abstain from antioxidant supplements (e.g., coenzyme Q-10, vitamin E) for the duration of the study.

Exclusion Criteria:

1. A primary psychiatric diagnosis other than BD (e.g., Schizophrenia)
2. Meet DSM-5 criteria for substance use disorder (other than Tobacco Use Disorder) within the past 6 months.
3. Any uncontrolled neurological condition (e.g., epilepsy) that could confound the results of the study
4. Any history of brain injury with loss of consciousness greater than 5 minutes
5. Any history of mental retardation, dementia, or recent electroconvulsive therapy (in the past 3 months)
6. Any uncontrolled medical condition that may adversely affect the conduct of the study or jeopardize the safety of the participant
7. Hepatocellular disease as indicated by plasma levels of liver transaminases (aspartate transaminase, alanine transaminase) greater than 3 times the normal range
8. Renal insufficiency as indicated by plasma levels of creatinine greater than 2 times the normal range
9. Concomitant use of nitroglycerine, carbamazepine, or any other medication deemed to be hazardous if taken with N-Acetylcysteine (NAC).
10. Medication dose changes of ≥ 20% ≤ 2 weeks prior to testing
11. Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception
12. Current suicidal or homicidal risk
13. Baseline scores greater than 35 on the Montgomery-Asberg Depression Rating Scale or greater than 25 on the Young Mania Rating Scale
14. Has taken NAC in the last month or experienced adverse effects/allergic reaction from it at any time
15. Significant claustrophobia and/or past negative experiences with MRI
16. Presence of non-MRI safe materials in the body (e.g., ferrous metal implants, pacemaker)

Adverse Event data were collected over each participant's total study duration. This duration was a 6-week period for each participant (i.e., 2, 2-week condition periods separated by 1, 2-week washout period). Adverse event data collection took place for the entirety of the study which was 1 year.

At each study visit following the initial screening visit, study participants were assessed by the study medical doctor for any adverse events. Adverse events were recorded, rated on a severity scale, determined their relation to the study medication, and any treatment or intervention needed was discussed. The study medical doctor followed up with all previously reported adverse events at the following visits to determine if the events had ceased.

Double-blind