Cannabis for the Prophylactic Treatment of Migraine

Inclusion Criteria: * Subject is willing and able to give signed informed consent. * Male and female patients aged 25 years or older. * History of migraine for at least 12 months as diagnosed by the International Classification of Headache Disorders (ICHD-3). * Chronic migraine for at least the previous 3 months prior to screening, as diagnosed by ICHD-3. * Migraine preventative medications (including Botulinum toxin injections) are permitted if dose is stable for the 3 month period prior to randomization, and no change to dose is planned for the entire duration of the study. * Using a reliable method of contraception for females of child-bearing age. * Failure of at least 2 prior migraine preventatives, either due to lack of efficacy with an appropriate trial of the medication, or due to lack of tolerability. * Able to follow study procedures, fill out headache diaries, and complete questionnaires. * Completion of at least 90% of the headache diary during the one month baseline period. Exclusion Criteria: * Other active primary headaches, such as cluster headache, hemicrania continua, etc. * Any secondary headache, such as headache related to intracranial hypertension, intracranial hypotension, hydrocephalus, intracranial mass lesion, etc. * Pregnant, planning to become pregnant, or breastfeeding. * Active or significant history of major mental illness, including severe depression, or anxiety, and any history of psychosis or schizophrenia. * History of or current substance use disorder. * Regular use of cannabis for medical or recreational reasons during the previous 12 months. * History of significant cardiovascular or cerebrovascular disease, such as previous myocardial infarction, stroke, or peripheral vascular disease. * History of hypertension greater than 160/100 and not medically treated. * Any past history of seizure disorder. * Liver disease or liver enzymes two or more times the upper limit of normal at baseline. * Severe renal disease or GFR more than 30% below expected. * Any disorder or condition leading to hypersomnolence or excessive daytime drowsiness, such as narcolepsy, excessive use of sedatives/hypnotics, etc. * Any other medical condition that in the opinion of the investigators may pose a health risk to the subject if entered into the clinical trial. * Use of interventions or devices, such as nerve blocks, sphenopalatine ganglion blocks, vagal nerve stimulators, and transcranial magnetic stimulators during the baseline period (weeks -4 to 0). These treatments will also be prohibited during the period of therapy (weeks 0 to 12). * Use of transitional therapies such as a course of steroids or a dihydroergotamine protocol during the baseline period (weeks -4 to 0). These treatments will also be prohibited during the period of therapy (weeks 0 to 12). * Overuse of triptan, dihydroergotamine, opioid, or barbiturate medications, defined as 10 or more days per month in the 3 months prior to randomization. * Overuse of simple analgesics (such as acetaminophen, ibuprofen, aspirin), and non-steroidal anti-inflammatories (such as naproxen, ketorolac, diclofenac, etc.) defined as 15 or more days per month in the 3 months prior to randomization.