Migraines suck. Whether they hit suddenly or are triggered by specific stimuli, they're much worse than just a nasty headache. 

Unfortunately, they're quite common. Roughly 12 percent of the population have had a migraine, while four million adults in the United States have over 15 migraines a month. Needless to say, migraines - which can lead to altered perception, increased sensitivity to lights and sounds, and nausea - are a debilitating condition that can seriously impact one's quality of life.

It should come as no big surprise, then, that many sufferers throughout history have turned to cannabis for migraine relief

Headaches were, in fact, one of the earliest known medicinal uses for marijuana, with references dating back to the 6th and 7th centuries CE. For migraines specifically, Sir William Osler - considered to be one of the fathers of modern medicine - said: “Cannabis… is probably the most satisfactory remedy."

Until the 1940s, marijuana was included in the United States Pharmacopeia for treatment of migraines. Even after marijuana preparations were dropped from the Pharmacopeia, the Journal of the American Medical Association remained a proponent of its use in treating migraines. But for reasons that have nothing to do with its effectiveness, marijuana is no longer considered a first-line treatment for migraines in the medical community.

The cause

The excruciating pain of a migraine is thought to result from inflammation of the brain’s outer casing, the “dura mater” (which means “tough mother” in Latin). The dura mater is a thin leather-like helmet that sits just under the skull and protects the brain from injury. It’s believed that this inflammation results from the activation of the brain’s trigeminovascular system, which is a made up of a bundle of brain cells and their connections to blood vessels in and around the head. It’s abnormal cross-talk between the brain and the blood vessels that causes migraines.

Migraines are associated with dilated blood vessels, and a couple key players are involved. Neuropeptides, which function as neurotransmitters, irritate and dilate blood vessels. Also, the gas nitric oxide triggers more neuropeptide release from key brain cells and dilates blood vessels. Together, they lead to the onset of migraine and prolong its duration.  

Endocannabinoids and migraine

The body’s own cannabinoids, known as endocannabinoids, play a critical role in regulating the trigeminovascular system. Lower levels of endocannabinoids are thought to increase risk for developing migraines because the primary endocannabinoids, 2-AG and anandamide, exert control over blood vessel tone by regulating neuropeptide release from cells and nitric oxide production. Therefore, it’s no surprise that people who suffer from migraines often have lower endocannabinoid levels in their cerebral spinal fluid.

However, it’s still unclear if migraines themselves reduce endocannabinoid levels or if low levels cause migraines. The strongest evidence in favor of low levels of endocannabinoids causing migraines stems from genetic studies which find that variation in the gene for the cannabinoid type I receptor, known simply as CB1 receptors, increases risk for developing migraines.

And it makes logical sense. Activation of CB1 receptors by 2-AG or anandamide can dampen the activity of the trigeminovascular system. This reduction in trigeminovascular activation protects against migraines.

Why cannabis can help

THC is the main psychoactive ingredient in cannabis. It gets you high by acting on CB1 receptors. But, by the same action, it can also dampen trigeminovascular activity. Furthermore, CB1 activation can reduce neuropeptide release and nitric oxide production. So, if you can activate your CB1 receptors, you may be able to both prevent migraines, or at least alleviate them once they’ve occurred.

To gain insight into if and how cannabis may treat migraines, researchers turn to rodents. You can simulate a migraine in rats by causing dilating the blood vessels of the dura mater. It’s clear that they’re unhappy and in pain because their time spent running on the wheel is greatly reduced. After all, you’d likely do the same.

Researchers found that THC increased the amount of time spent on the wheel after simulated migraine, and this rescue from migraine required CB1 receptors. However, in this case, THC was only effective if it was given just prior to when the migraine began. THC lost its effectiveness if the rats were experiencing migraine-like symptoms before they were administered THC. From this study, it appears that THC worked best as a preventative treatment by acting on CB1 receptors.

Evidence in humans  

The most convincing evidence of marijuana’s effectiveness in treating migraines comes from a human study published in 2016 in the journal, Pharmacotherapy. In it, 121 migraine suffers were tested. These individuals had been suffering from migraines for an average of 14 years, long enough to have attempted numerous ineffective treatment strategies. They entered the study averaging 10.4 migraines per month.

Within one-to-three years, subjects who'd started using medical cannabis recorded an average migraine frequency of only 4.6 headaches/month, a reduction of over 50 percent from before using cannabis as a migraine treatment. Further, more than 10 percent of the subjects reported that cannabis actually helped them eliminate migraines once they started.

Smoking cannabis was reported to be the most effective consumption method for both prevention of migraines and termination of migraines. This likely reflects the rapid onset of marijuana’s effects from smoking compared to topicals or edibles. Smoking also allowed the subjects to more effectively titrate their needed dose.

Despite these seemingly positive effects, only 48 percent of participants reported that cannabis helped with their migraines. This highlights an important point: there’s a great deal of variability in marijuana’s medicinal efficacy that depends on the user, the type of cannabis used, and the root cause of the medical ailment. Notably, however, the side effects were minimal. The most frequent side effect was feeling sleepy. It was observed in two participants.

So, if after years of unsuccessful treatment for migraines, what’s the harm in giving cannabis a shot?

Josh Kaplan, Ph.D. is a neuroscientist at the University of Washington and freelance science writer specializing in the science of cannabis. Visit neurokaplan.com to learn more.