Short- and Long-Term Effects of Cannabis on Headache and Migraine, Carrie Cuttler et al., 2019

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

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

Journal of Pain, 2019.

doi : 10.1016/j.jpain.2019.11.001



 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), THC, CBD, or dose contribute to changes in these ratings. Finally, we explored evidence for tolerance to these effects. Archival data were obtained from StrainprintTM, 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 analyze 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.

Perspective : 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.

Keywords : Medical Marijuana; THC; CBD; Headache; Migraine



Use of cannabis to treat headache dates back hundreds to thousands of years [15,23], and is currently widespread among medical cannabis users [2,26]. Nearly 36% of medical cannabis users reported using cannabis to treat headache/migraine; moreover, they retrospectively reported an average 3.6-point decrease (on a 10-point scale) in headache severity after cannabis use [26]. Similarly, 40% of patients for whom medical cannabis was recommended for migraine reported a positive effect, with a decrease in migraine frequency from 10.4 to 4.6 migraines/month [22]. Moreover, another study found that approximately 2/3 of cannabis users indicated slight to substantial decreases in use of other migraine medications after initiating medical cannabis use [21]. These studies suggest that many individuals are using cannabis to treat headache and migraine, and that users experience some therapeutic effect. To date, however, there has only been one randomized, double-blind study of cannabinoid treatment for headache or migraine. Conducted in 30 outpatients with medication overuse headache, this study showed that nabilone (a synthetic cannabinoid) was more effective than ibuprofen in reducing pain intensity, reducing intake of other analgesics, and increasing quality of life [20].

Preclinical studies also suggest that cannabinoids may be effective for migraine. Using a rat model of migraine (in which dural inflammation suppresses wheel-running), sumitriptan, morphine, and delta 9-tetrahydrocannabinol (THC) each prevented migraine-suppressed wheel running [12,13]. However, rats given morphine repeatedly showed tolerance to morphine‟s antimigraine effect and increased sensitivity to further migraine induction [12], echoing the tolerance and medication overuse headache phenomena observed in human migraineurs [25,28]. In contrast, rats did not develop tolerance to THC‟s anti-migraine effect [12]. THC likely acts similarly to the endocannabinoid anandamide, which inhibits vasodilation of dural blood vessels and decreases release of calcitonin gene-related peptide from trigeminal neurons, two of the many mechanisms that are known to contribute to migraine [1]. The fact that patients with chronic migraine have been found to be anandamide-deficient further suggests that an underresponsive endocannabinoid system contributes to migraine susceptibility [10].

In the present study, we used a large archival dataset obtained from the medical cannabis app StrainprintTM to address questions regarding the perceived efficacy of cannabis in medical cannabis users who used the app to track changes in headache or migraine from before to after cannabis use. The primary objective of the present study was to examine whether inhaled cannabis would decrease headache and migraine severity ratings. The second objective was to explore factors that predict such decreases, including gender, type of cannabis, CBD and THC content, and dose. Based on preclinical studies showing greater antinociceptive sensitivity to cannabinoids in females compared to males [6], we predicted that the perceived analgesic efficacy of cannabis would be greater in women than men. Given that CBD enhancement of THC-induced antinociception has been found in animals [5,14], and suggestions that the ratio of THC to CBD modulates some cannabis effects [24,29], we also explored interactions between THC and CBD in predicting change in headache and migraine severity ratings.
The third objective was to investigate the development of tolerance to the putative effects of cannabis on headache and migraine, and to examine change in baseline headache/migraine severity ratings as a function of the repeated use of cannabis to manage these symptoms. We included this objective because tolerance to cannabis among chronic cannabis users has been well-documented [9,19], and the phenomenon of medication overuse headache, which occurs in approximately 15% of migraine patients [28], may be related to the development of tolerance to migraine medications.