Cannabidiol (CBD) to prevent chronic migraine

Cannabis for the Prophylactic Treatment of Migraine: a Randomized Double-Blind Placebo-Controlled Clinical Trial

This trial will test whether a daily cannabidiol (CBD) pill can reduce headaches in adults with chronic migraine.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 25 Years and up
• Sex: All
• Sponsor: University of Calgary (Academic / other)
• Locations: 1 site (Calgary, Alberta)
• Trial ID: NCT03972124 on ClinicalTrials.gov

What this trial studies

Adults with chronic migraine will be randomized in a double-blind, placebo-controlled design to receive either 100 mg CBD, 200 mg CBD, or placebo taken once daily. Eligible participants must be 25 or older, have chronic migraine for at least 3 months, and have failed at least two prior preventive medications; stable preventative medications are allowed. Participants will complete a baseline headache diary and continue daily diaries during treatment while investigators monitor headache frequency, severity, and safety outcomes. The trial compares two fixed CBD doses against placebo to measure potential preventive effects and tolerability.

Who should consider this trial

Good fit: Adults aged 25 or older with a diagnosis of chronic migraine for at least 3 months who have failed at least two preventive medications and can complete headache diaries and study visits.

Not a fit: People with episodic migraine, those younger than 25, pregnant or breastfeeding individuals, or those with contraindications to cannabinoids are unlikely to benefit from joining this trial.

Why it matters

Potential benefit: If successful, daily CBD could reduce the frequency or severity of chronic migraine attacks and offer an alternative for people who have not responded to or tolerated other preventives.

How similar studies have performed: Prior evidence for cannabis or CBD in migraine is limited and mixed, so this randomized placebo-controlled trial aims to provide higher-quality data.

Eligibility criteria

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.

Where this trial is running

Calgary, Alberta

• CHAMP Research (Calgary Headache Assessment & Management Program) — Calgary, Alberta, Canada (Recruiting)

Study contacts

• Study coordinator: CHAMP Research (Calgary Headache Assessment & Management Prog)

Conditions Chronic Migraine