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Caffeine and Headache: Exploring the Multifaceted Relationship

Hussein M, Hassan A, Al-Azayem SA, Thuraiaiyah J, Schytz HW, Nasser AMA, Magdy R

Brain and behavior, 2026

Abstract

Purpose: To explore the multifaceted relationship between caffeine and headache disorders, focusing on its dual role as both an analgesic and a potential trigger and to summarize the mechanisms underlying its anti-nociceptive effects.

Method: This narrative review synthesizes evidence from experimental, clinical, and epidemiological studies on caffeine's pharmacological actions, its role in adenosine receptor modulation, and its impact across different headache types, including migraine, hypnic headache, post-dural puncture headache (PDPH), medication-overuse headache (MOH), and caffeine-withdrawal headache.

Findings: Caffeine exerts analgesic effects through adenosine receptor antagonism, prostaglandin inhibition, GABA-A modulation, and cholinergic facilitation while also enhancing the efficacy of analgesics such as nonsteroidal anti-inflammatory medications (NSAIDs), acetaminophen, and opioids. In migraine, it demonstrates a dual role, relieving attacks by counteracting adenosine-mediated vasodilation and improving drug absorption yet potentially triggering them when intake is excessive or inconsistent due to mechanisms such as magnesium depletion, diuresis, and sleep disruption. Beyond migraine, caffeine shows therapeutic benefit in hypnic headache and PDPH, but chronic use may contribute to MOH through neuroadaptive changes. Abrupt cessation of caffeine often provokes caffeine-withdrawal headache.

Conclusion: Caffeine plays a complex role in headache disorders, acting as…

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