CBD and migraine: what the first controlled trial found

Migraine is a neurological disease that comes in attacks, which sets it apart from an ordinary bad headache. The Inserm report on migraine puts it at about 15% of the population: 20% of women and 10% of men. Left without effective treatment, an attack lasts 4 to 72 hours.

Tension-type headache is more common. Its pain is diffuse and steady, with no throbbing and no nausea, and Inserm notes that migraine-specific treatments have no effect on it. Studies that mix the two kinds of pain produce results that are hard to interpret.

Medication-overuse headache is a third picture worth knowing. It appears when someone with migraine takes painkillers too often, and becomes an almost daily pain. Treatment means stopping the medicine involved, sometimes in hospital, so adding yet another product to frequent use goes the wrong way.

The authors note that no randomised trial had previously tested a cannabinoid against an acute migraine attack. Their team at the University of California San Diego enrolled 92 adults with migraine. Each person treated up to four attacks, one per product, in random order and blind to which one they received: a vaporised flower with 6% THC, one with 11% CBD, a blend of the two, or a placebo flower. The dose, four inhalations, was taken within four hours of the attack starting, and at least one week separated two treated attacks. The study, funded by the Migraine Research Foundation and the US National Institutes of Health (NIH), covered 247 treated attacks in all.

The primary endpoint was the proportion of attacks in which pain, moderate or severe at the outset, had fallen to mild or none two hours later.

For a French consumer, the result carries several limits. CBD was vaporised as flower, and no oil or capsule was tested. The "CBD" flower itself held 0.35% THC, a little over the French limit, and each participant treated just one attack per product. Most importantly, both arms that worked contained 6% THC. The decree of 30 December 2021 caps Δ⁹-THC in authorised hemp at 0.30%, so a 6% flower is a controlled drug. This threshold is explained in our article on the legal THC level.

Research interest comes from the endocannabinoid system, a network of receptors involved in relaying pain signals. It is a reason to study the question and proves nothing about efficacy.

The rest of the evidence is weaker. A review published in 2022 in Frontiers in Neurology pooled 12 publications covering 1,980 participants in Italy and the United States. Most dealt with medical cannabis containing THC, often without a control group. The authors judge the results promising and call for well-designed trials. They also report an unfavourable signal. In one study they cite, 81% of people with migraine who used medical cannabis had medication-overuse headache, compared with 41% of non-users. This is an association and does not show that cannabis is the cause.

In 2020, a study in the Journal of Pain examined 12,293 sessions logged in a tracking app for headache, and 7,441 for migraine. After inhaling cannabis, users reported their pain roughly halved. Nothing controlled for placebo or checked the product, and the effect seemed to wane over time as doses rose. The figures record user reports and say nothing about the molecule's own action.

No study among them examines a THC-free CBD oil, which is what French shops sell.

MILDECA points out that products containing CBD may not make therapeutic claims unless authorised as medicines, on pain of criminal penalties. Under Article L5111-1 of the French Public Health Code, any product presented as having curative or preventive properties is a medicine. An oil sold "for migraine" would thus be a medicine without authorisation.

Epidyolex, prescribed for rare childhood epilepsies, is the only cannabidiol medicine authorised in France, and migraine is not among its indications. What the legal framework allows anyone to say on the subject is set out in our article on CBD and pain.

The liver clears CBD through the same enzymes it uses for many medicines. According to the Epidyolex summary of product characteristics, published by the European Medicines Agency, CBD inhibits the CYP2C19 enzyme and can thus raise blood levels of other drugs. The mechanism is explained in our article on the grapefruit effect.

Three simple rules follow for anyone with migraine:

• never stop or space out a prescribed preventive treatment in order to switch to CBD;
• mention any CBD product to your doctor or pharmacist, as you would a food supplement;
• see a doctor if your attacks change pattern or grow more frequent, or if you take painkillers on more than a few days a week.