Signatures of N-Ac for Non-Suicidal Self-Injury in Adolescents

This study is a double-blind, placebo controlled, 4-week course of two-tiered N-acetylcysteine (NAC) dosing focused on identifying the optimal dose to achieve meaningful change in measurable biomarkers (glutathione and glutamate).

This design will allow us to confirm acute biological changes, select the optimal dose for achieving biological effects, and examine dose/concentration-response relationships with respect to biological markers and pharmacokinetics.

Brief schedule of activities: Subjects will be recruited through community and clinical settings and screened over the phone. There will be a total of 4 in-person visits and two sets of on-line study activities.

Eligible participants will be assigned to one of 3 groups (double-blinded): a low-dose NAC group (3600 mg/day), a high-dose NAC group (5400mg/day), and placebo (PBO). The study intervention period is 4 weeks. Total participation is up to 8 weeks, depending on the length of time between Day 0 and Day 1.

The investigators will recruit 36 adolescents and young adults aged 16-24 years. There will be 12 participants in each group (PBO, 3600mg/day, 5400mg/day). The investigators will use a minimization procedure to ensure that the participants in these 3 groups will have similar age, clinical severity and medication status.

Inclusion criteria

• Current frequency of at least one NSSI episode in the past 2 months
• ≥ 5 past episodes of NSSI with significant tissue damage (e.g. scars present)
• Psychotropic medications are dose-stable for 1 month
• Ability to understand study procedures and to comply with them for the entire length of the study

Exclusion criteria

• Any MRI contraindications (e.g. metal plates, claustrophobia, braces, implanted devices)
• Any current serious medical illness as defined by medical history
• Current Substance Use Disorder (except Tobacco Use Disorder)
• Primary psychotic disorder (e.g. schizophrenia, schizoaffective disorder, schizophreniform disorder)
• Neurodevelopmental disorder such as mental retardation or autism
• Changes in psychotropic medications in past 1 month
• Taken NAC or glutathione on a regular basis in the past 6 months
• Currently pregnant, planning to become pregnant, currently breastfeeding, or unwillingness to use contraception throughout the study.
• Allergy/sensitivity to N-acetylcysteine.
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.