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Are Migraines Due to a Dysfunction of Cannabinoid Neurons?

Recent research has found a link between migraine pain and the endocannabinoids.

Migraines are the second leading cause of disability in individuals under the age of 50 in the world. If you suffer with these headaches, you are not alone. The consequences are considerable: chronic and episodic migraines negatively impacting physical health, quality of life, interpersonal relationships, productivity, and financial security. The currently available medications for acute migraine pain are rarely effective for most migraineurs. Even the triptans, which were developed specifically for the treatment of acute migraine headache, have limited effectiveness. In addition, triptans must be taken as soon as possible after the first appearance of a symptom. If you miss the window of effectiveness, then you suffer with the consequences. Furthermore, many available medications, especially aspirin or ibuprofen, produce unfavorable side-effects or induce rebound migraines.

The epidemiological evidence for cannabis’s effectiveness is highly variable. One small survey study reported that 36% of recreational cannabis users treat their migraines with cannabis. Another study found that 85% of individuals using medically prescribed cannabis, as opposed to recreational use only, reported a decrease in migraine frequency. The higher percentage may be due to the fact that these subjects sought out a medical recommendation. These older studies were small and limited by the participants' limited access to cannabis products.

A recent study (Gibson et al., 2021) sampled 589 adult cannabis users living in states with full legal access. The migraineurs in these states reported significantly more migraine relief from cannabis compared to non-cannabis products, even after controlling for migraine severity.

What might explain the effectiveness of cannabis?

Studies suggest that the brain’s endogenous cannabis system modulates migraine-associated pain pathways. The newest class of anti-migraine drugs, those that act as CGRP synaptic inhibitors, involve manipulation of endocannabinoid pathways in the brainstem. An endocannabinoid deficiency is may contribute to the pathophysiology of migraine according to one recent publication. Experimental and clinical studies have discovered links between dysregulation of endocannabinoid signaling and migraine headache. Apparently, the level of anandamide, one of the primary endocannabinoid neurotransmitters in the brain, is significantly reduced in the brain and body of patients with chronic migraine. The reduced levels of this endocannabinoid may facilitate the experience of the body aches and pains that are often associated with migraines.

Will everyone benefit from cannabis?

Migraines are 2.5 times more common in women than men. However, men experience greater cannabis-induced analgesia than women. Therefore, sex-dependent differences in cannabis's analgesic effects are an important consideration when using it for relief of acute migraine pain. Particular strains may be more efficacious in reducing migraine symptom severity. Strains high in THC and low in CBD may be beneficial due to the analgesic, anti-inflammatory, and anti-emetic properties of THC that are not shared by CBD (in spite of the hype on the internet). In another study, migraineurs taking 200 mg of THC per day experienced a greater improvement in migraine symptoms compared to migraineurs taking 25 mg of the tricyclic antidepressant amitriptyline or 400 mg of ibuprofen. Future studies will need to determine the best the optimal dose of cannabis, as well as the most effective blend of THC and CBD, that are most effective at treating acute migraine pain.

© Gary L. Wenk, Ph.D.

I am the author of Your Brain on Food (3rd Edition, 2019; Oxford University Press) and a member of the Governor’s Medical Marijuana Advisory Committee for the State of Ohio.


Gibson LP et al (2021) Experience of migraine, its severity, and perceived efficacy of treatments among cannabis users. Complementary Therapies in Medicine 56: 102619

Cooper ZD, Margaret H (2016) Sex-dependent effects of cannabis-induced analgesia. Drug and Alcohol Dependence, 167: 112.

Rhyne DN et al., (2016) Effects of medical marijuana on migraine headache frequency in an adult population. Pharmacotherapy, 36: 505.

Baron EP (2018) Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: an update on current evidence and cannabis science. Headache, 58: 1139.