Parkinson's disease is a common neurodegenerative disorder in which patients experience progressive motor disability and many disabling non-motor symptoms. Recent studies have consistently found that people who do not use caffeine are at higher risk of developing Parkinson's disease. This suggests that caffeine may have potential as a treatment for PD.

In a pilot study of caffeine for daytime sleepiness in PD, there was evident benefit on the motor manifestations of disease. There have been other lines of evidence that have suggested caffeine could be useful in PD. This study is to evaluate the efficacy of caffeine 200 mg BID vs matching placebo for motor and non-motor aspects of disease. This will be in three stages. In the first six-month stage, medications will be held constant, to see whether caffeine does have motor benefits. Then we will perform a four-year extension stage to define if the effects of caffeine persist (or even magnify), and to see if caffeine helps reduce dose of other PD meds and/or prevents their side effects. Finally, we will finish with a six-month stage in which we will place all patients on caffeine - this will allow us to assess caffeine's use in later disease, but more importantly, will assess whether early use of caffeine produces long term changes beyond its immediate effects.

Inclusion Criteria:

All patients must have idiopathic PD diagnosed as parkinsonism according to the UK brain bank criteria, and PD considered the likeliest underlying cause according to the treating physician. Other inclusion criteria include:

1. PD diagnosis: between 6 months and 8 years
2. Hoehn and Yahr stage I-III
3. Age at least 45 and less than 75 (to optimize survival over the 5-year trial).
4. Receiving symptomatic therapy for PD for at least 6 months. Dose must have been stable over the previous 3 months.

Exclusion Criteria:

1. Caffeine intake >150 mg per day (i.e. more than one cup of filtered coffee per day) or prescribed adenosine antagonists - caffeine intake will be measured by a standardized intake questionnaire. Intake will be converted into estimated caffeine mg dose by standard caffeine-content charts.
2. Active peptic ulcer disease, or symptomatic gastroesophageal reflux disease.
3. Supraventricular cardiac arrhythmia (such as atrial fibrillation or atrial flutter) - Electrocardiogram will be measured at baseline to rule out supraventricular tachycardia.
4. Uncontrolled hypertension - systolic bp >170 or diastolic bp >110 on two readings.
5. Pre-menopausal women who are not using effective methods of birth control
6. Cognitive impairment, defined as MoCA <23/30.
7. Moderate-Severe Depression, as defined by a Beck Depression Inventory score of >19.
8. Changes to antiparkinsonian medication in the last 3 months, or changes to antiparkinsonian medication are anticipated during the next six months.
9. Current use of lithium or clozapine (pharmacokinetic interactions).