Evidence-based medicine depends on distinguishing between pharmacological effects and placebo effects in randomized controlled trials (RCT). This proposal seeks to rigorously investigate fundamental questions concerning pharmacological effects, placebo effects and their interactions. Relief of symptoms of acute migraine will be the test condition for this scientific experiment because of migraine's evident clinical significance and the possibility of using participants as their own control during sequential acute migraine attacks. Our overall goal is to elucidate how the pharmacological effects of 100 mg rizatriptan (an FDA-proven effective medication for acute migraine) and the effects of placebo treatment can be modified by varied knowledge and/or expectation ("contextual") conditions. Such knowledge has the possibility to suggest potentially more efficient methodologies to test new medications that can be used to augment and enhance the apparatus of the RCT.

General Aim: To elucidate and clarify what is a pharmacological effect and what is a placebo effect, how such effects vary in different knowledge/expectations contexts, and mutually constitute one another and interact.

General Hypothesis: The measured pharmacological effect of an effective medication (rizatriptan) and the measured effect of placebo treatment are determined significantly by different knowledge/expectations contexts.

Inclusion Criteria:

• Patients will be considered for this study if they suffer from classical or common migraine for at least 3 years.
• Candidates will recruited from the clinical case load of Dr. Zahid Bajwa and the headache and pain management center at BIDMC.
• Only patients older than 18 years of age,
• Able to communicate clearly in English,
• Able to give an informed consent will be considered as candidates.
• No limitation of gender or race is justified and thus, it is open to all patients fulfilling criteria for migraine type headache.
• Patients will be able to withdraw from the study at any time.
• They will be included in the study if they meet the criteria for migraine with or without aura (Headache-classification-committee-of-the-International-Headache-Society 1988), if they had >4 migraine attacks each month for the previous year.

Exclusion Criteria:

• Exclusion criteria will include cardiovascular or cerebrovascular disorders,
• Cardiac risk factors and liver disease,
• Uncontrolled hypertension,
• Peripheral and central nervous system disorders that affect sensory functions (such as sensory neuropathies and chronic pain),
• The use of opiates or other analgesic drugs for any reason, and the use of other prophylactic anti-migraine drugs.
• Any patient with active hepatitis or elevated liver enzymes (based on their BIDMC medical record) will be excluded as well.
• Employees who are under the direct supervision of the investigators will not participate in the study.

Patients were not asked whether or not they thought the pill they took was maxalt or placebo. Thus, it is not possible to determine their actual level of expectation.