Glutathione is an important nutrient for brain function and loss of glutathione has been implicated in Parkinson's disease. Glutathione is an antioxidant made in the body out of three amino acids, the nutrients that make up protein. This study will determine whether administration of either dose of glutathione, as a nasal spray, improves PD symptoms over time in a population of individuals with Parkinson's disease (PD).

The study begins with a pre-screening telephone interview. During this conversation participants will be asked a series of questions that will help us identify whether they are eligible for participation in this study. The pre-screening interview process will take approximately 10 minutes and will include all screening criteria that does not require clinical or laboratory examination

All routine research visits will take place at Bastyr University Campus (Kenmore, WA). Participants will be asked to schedule visits at approximately the same time of day each visit .If they are on medications, we would like them to take their medications as they normally would on the day of the visit. Participants will be randomly assigned to one of three different study groups- a low dose group, a high dose group, or a placebo group.

Study participants will invited to volunteer for two magnetic resonance imagine (MRI) scans as part of this study, an optional part of study participation. For those who volunteer and qualify, MRIs will be performed at the University of Washington Radiology Department early in the morning. One scan will be taken at baseline before taking glutathione and the second upon completion of the study medication. There will be a separate consent form for those who participate in the imaging portion of this study. Among the participants who volunteer, the first 15 to qualify for an MRI scan will be scheduled according to MRI availability.

If participants are enrolled in the study, they will be asked to keep a daily log of actual frequency of administration of study medication, if any, as well as any changes in their PD symptoms, any adverse events they might experience, and their general well-being. We are giving participants enough medication to last four weeks, until the date of their next appointment. The medication should be taken three times a day (morning, afternoon, and evening).

Visit 1- Baseline: (Approximately 1 hour)

• Urine sample
• Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..
• Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS), which involves assessing degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.
• Participant will be taught how and when to administer the study medication and be given a 1-month supply.

Visit 2- Week 4 follow-up: (Approximately 1 hour)

• Urine sample
• Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..
• Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) and Webster-Step Second test involve assessing degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.
• Participant will be asked to return any unused study medication and applicator tips from the first month of the study and be given the next 1-month supply.
• We will inquire about medication changes and collect medication use logs.

Visit 3- Week 8 follow-up: (Approximately 1/2 hour)

• Participant will be asked to return any unused study medication from the second month of the study and be given the next 1-month supply.
• We will inquire about medication changes and collect medication use logs.

Visit 4- Week 12 follow-up: (Approximately 1 hour)

• Urine sample
• Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..
• Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) to assess degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.
• Participants will be asked to return any unused study medication from the third month of the study.
• We will inquire about medication changes and collect medication use logs.

Visit 5- Week 16 follow-up: (Approximately 1 hour)

This visit is included to determine whether there are any lasting effects of the study medication one month following discontinuation of use. The visit will include:

• Urine sample
• Venipuncture (blood draw, (40 mL / ~3 Tbsp) to assess blood antioxidant status..
• Clinical assessment of PD severity: Unified Parkinson's Disease Rating Scale (UPDRS) which involves assessing degree of tremor, ability to walk across the room, questions about ability to function independently (i.e. button your own shirt, feed yourself), and questions about mental health, including depression and intellectual impairment.

Overall, approximately 5 hours will be required for study participation. Blood draws will occur at most, but not all visits, and will not exceed 4 Tbsp per month.

Inclusion Criteria:

• Diagnosis of PD made by a clinical neurologist within the previous 10 years
• A modified Hoehn & Yahr Stage <3
• Age >21
• Subjects must be able to attend study visits at baseline, weeks 4, 8, 12, and 16.
• Subjects must be able to demonstrate, or have a caregiver administer, medication.
• Dose and frequency of pharmaceutical medications must be stable for 1 month prior to enrollment.
• Dose and frequency of naturopathic medications must be stable for 1 month prior to enrollment.
• Diet, exercise, and medications must be kept constant throughout participation in the study. (Medication changes considered essential by a participant's physician will be permitted and recorded).
• Ability to read and speak English.
• MRI cohort: Additional inclusion criteria specific to MRI.

Exclusion Criteria:

• Dementia as evidenced by a Montreal Cognitive Assessment score of less than 24.
• Diseases with features common to PD (e.g., essential tremor, multiple system atrophy, progressive supranuclear palsy)
• Epilepsy
• A history of stroke
• The presence of other serious illnesses
• Respiratory disease (e.g. asthma, COPD)
• A history of brain surgery
• A history of structural brain disease
• A history of intranasal telangiectasia
• Supplementation with glutathione, and agents shown to increase glutathione, will not be permitted and their use will necessitate a 90-day washout period; this will be required for all forms of glutathione and the glutathione precursor, N-acetylcysteine.
• Pregnant or at risk of becoming pregnant (i.e., unwilling to use birth control if a sexually active, pre-menopausal female). Urine pregnancy tests will be administered to pre-menopausal women.
• MRI cohort: Additional exclusion criteria specific to MRI.