Cannabis tied to rebound headaches in chronic migraine patients – Stanford study

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Migraine patients who used cannabis were more likely to develop ‘rebound’ or medication overuse headaches than those who did not use cannabis, a single-centre chart review by Stanford University suggested, writes Judy George for Medpage Today. The study finds moderate evidence supporting the use of cannabis for the treatment of chronic pain.

In an analysis of 368 patients with chronic migraines, current cannabis use predicted cases of medication overuse headache (OR 5.99, 95% CI 3.45-10.43, P<0.0001), reported Dr Niushen Zhang and Dr Yohannes Woldeamanuel, both of Stanford University School of Medicine in California, in an abstract released on 1 March 2021 in advance of the American Academy of Neurology annual meeting.

Medication overuse headache is a result of frequent use of pain medications for headaches. "Cannabis affects the endocannabinoid system in the brain, which plays a role in pain processing," Zhang and Woldeamanuel said, according to Medpage Today.

"There is moderate evidence to support the use of cannabis for the treatment of chronic pain," they added. "However, there is emerging anecdotal clinical evidence that use of cannabis may lead to medication overuse headache."

Recent research from Washington State University in Pullman showed that inhaled cannabis reduced self-reported migraine severity 49.6%. That study found no evidence of cannabis leading to overuse headache, but researchers noticed patients using larger doses of cannabis over time, indicating possible tolerance to the drug.

The Medpage Today article continues: Zhang and Woldeamanuel used the Stanford Research cohort discovery tool between 2015 and 2019 to evaluate adults who had chronic migraines for at least one year. Chronic migraine was defined as 15 or more headache days per month. Of 368 patients in the study, 150 were using cannabis.

From each patient's chart, the researchers extracted data about age, sex, migraine frequency, current chronic migraine duration, current cannabis use duration, overused acute migraine medications, and duration of current medication overuse headache.

They used logistic regression to identify variables predicting overuse headache while controlling for the remaining predictors.

Overall, 212 patients had medication overuse headache and 156 did not. Significant associations were seen between current cannabis use, opioid use, and overuse headache.

A bi-directional relationship between cannabis and opioid use also emerged. "Use of one increased use of the other," Zhang and Woldeamanuel wrote.

Analysis showed two clusters of chronic migraine patients, with patients in one cluster being younger and having less migraine frequency, higher overuse headache burden, and more current cannabis and opioid users than the other.

A limitation of the study was its retrospective nature, the researchers noted, reports Medpage Today. Longitudinal studies are needed to further explore relationships between cannabis and overuse headache in chronic migraine patients, they said.


The Stanford University study is not available yet, but below is the abstract for last year’s Washington State University article, which was published in The Journal of Pain in 2019. This is the reference for the Stanford University study:

Reference: Zhang N and Woldeamanuel Y “Medication overuse headache in chronic migraine patients using cannabis: a case-referent study”. Abstract at American Academy of Neurology 73rd Annual Meeting; April 17-22, 2021.


Study details

Short- and Long-Term Effects of Cannabis on Headache and Migraine

Carrie Cuttler, Alexander Spradlin, Michael J Cleveland and Rebecca M Craft

Published in The Journal of Pain on 9 November 2019



  • Headache and migraine ratings were reduced by nearly 50% after using cannabis.
  • Men reported larger reductions in headache after cannabis use than women.
  • Cannabis concentrates were related to larger reductions in headache than flower.
  • Evidence for tolerance to effects of cannabis on headache and migraine was detected.
  • Evidence for medication overuse headache was not detected.


Use of cannabis to alleviate headache and migraine is relatively common, yet research on its effectiveness remains sparse.

We sought to determine whether inhalation of cannabis decreases headache and migraine ratings as well as whether gender, type of cannabis (concentrate vs flower), delta-9-tetrahydrocannabinol, cannabidiol, or dose contribute to changes in these ratings.

Finally, we explored evidence for tolerance to these effects. Archival data were obtained from Strainprint, a medical cannabis app that allows patients to track symptoms before and after using different strains and doses of cannabis.

Latent change score models and multilevel models were used to analyse data from 12,293 sessions where cannabis was used to treat headache and 7,441 sessions where cannabis was used to treat migraine.

There were significant reductions in headache and migraine ratings after cannabis use. Men reported larger reductions in headache than women and use of concentrates was associated with larger reductions in headache than flower. Further, there was evidence of tolerance to these effects.


Inhaled cannabis reduces self-reported headache and migraine severity by approximately 50%. However, its effectiveness appears to diminish across time and patients appear to use larger doses across time, suggesting tolerance to these effects may develop with continued use.


Medpage Today article – Cannabis Tied to Rebound Headaches in Chronic Migraine Patients (Open access)


American Academy of Neurology – 2021 Virtual Annual Meeting (Regitration required)


The Journal of Pain article – Short- and Long-Term Effects of Cannabis on Headache and Migraine (Open access)




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